Large‐scale meta‐analysis of infection risk with JAK–STAT inhibitors in 29,000 patients

Máté Krebs; Lili Gulyás; Karen Krisztina Fazekas; Benedek Nagy; Mária Veronika Kolonics; Fanni Adél Meznerics; Norbert Kiss; András Bánvölgyi; Péter Hegyi; Péter Holló; Lajos Vince Kemény

doi:10.1111/jdv.70508

. 2026 May 26;40(10):1662–1674. doi: 10.1111/jdv.70508

Large‐scale meta‐analysis of infection risk with JAK–STAT inhibitors in 29,000 patients

Máté Krebs ^1,², Lili Gulyás ^1,², Karen Krisztina Fazekas ², Benedek Nagy ¹, Mária Veronika Kolonics ^1,², Fanni Adél Meznerics ^1,², Norbert Kiss ^1,², András Bánvölgyi ^1,², Péter Hegyi ^2,^3,⁴, Péter Holló ^1,^✉, Lajos Vince Kemény ^1,^2,^5,^6,^✉

PMCID: PMC13613348 PMID: 42187316

Abstract

Introduction

Janus kinase signal transducer and transcription activator (JAK–STAT) inhibitors have revolutionized the treatment of immune‐mediated inflammatory diseases (IMIDs) of the skin, such as in atopic dermatitis, alopecia areata and vitiligo. Although several meta‐analyses have confirmed their efficacy, concerns remain about the risk of infection, as the JAK–STAT pathway plays a key role in immune defence. Previous meta‐analyses examined only selected, pre‐specified infection categories and have not comprehensively evaluated all reported infection types or compared systemic and topical agents.

Methods

We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) that reported infection‐related adverse events in patients treated with systemic or topical JAK–STAT inhibitors for IMIDs of the skin. The study followed the PRISMA 2020 and Cochrane guidelines (PROSPERO: CRD 42024615839). Overall risk ratios (RRs) with 95% confidence intervals (CI) were calculated using a random‐effects model.

Results

Seventy‐four RCTs were included, involving more than 29,000 patients. JAK–STAT inhibitors were associated with an increased risk of influenza (RR = 2.12, 95% CI 1.03–4.36), bronchitis (RR = 2.03, 95% CI 1.43–2.88) and herpes zoster (RR = 1.67, 95% CI 1.29–2.15) compared to a placebo. The risk was particularly elevated in patients with atopic dermatitis (influenza: 3.22, 95% CI 2.03–5.10, herpes zoster: RR = 2.00, 95% CI 1.34–2.99). No significant risks were identified for serious, fungal or opportunistic infections, and topical JAK–STAT inhibitors demonstrated a favourable safety profile comparable to vehicle controls.

Conclusions

This meta‐analysis provides a comprehensive assessment of the risk of infection associated with JAK–STAT inhibitors in IMIDs of the skin. Although overall safety is acceptable, clinicians should be aware of the higher infection risk of influenza and herpes zoster and should consider vaccination and preventive strategies for high‐risk patients with atopic dermatitis. The main limitation is that the included studies involved highly selected populations with few comorbidities and short follow‐up.

Keywords: abrocitinib, adverse reactions, atopic dermatitis, baricitinib, brepocitinib, delgocitinib, deucravacitinib, deuruxolitinib, filgotinib, gusacitinib, herpes zoster, immune‐mediated inflammatory diseases of the skin, infection risk, influenza, itacitinib, ivarmacitinib, JAK–STAT inhibitor, Janus kinase inhibitors, peficitinib, povorcitinib, ritlecitinib, ropsacitinib, ruxolitinib, tofacitinib, upadacitinib, zasocitinib

In this large meta‐analysis of 74 randomized controlled trials involving more than 29,000 patients, JAK–STAT inhibitors were associated with an increased risk of influenza, bronchitis and herpes infections, particularly herpes zoster, while an increased risk of serious opportunistic or fungal infections was not observed.

graphic file with name JDV-40-1662-g003.webp

Why was the study undertaken?

Evidence regarding the risk of infection associated with JAK–STAT inhibitors in immune‐mediated inflammatory skin diseases remains limited, as previous studies have not comprehensively assessed the wide range of infections. The present study addresses this gap, as the first meta‐analysis to evaluate more than 20 types of infections, including previously underreported conditions such as influenza, bronchitis and oral herpes.

What does this study add?

Atopic dermatitis showed the highest susceptibility, with JAK–STAT inhibitors significantly increasing the risk of influenza and herpes zoster compared to a placebo, and tripling the risk of herpes zoster compared to dupilumab.

What are the implications of this study for disease understanding and/or clinical care?

Despite these specific increases, no increased risk of serious, fungal or opportunistic infections was identified in the analysed RCTs, and topical JAK–STAT inhibitors demonstrated a favourable safety profile; however, these findings should be interpreted with caution, given the limitations of the included studies.

INTRODUCTION

Janus kinase signal transducer and transcription activator (JAK–STAT) inhibitors have revolutionized the treatment of immune‐mediated inflammatory skin diseases (IMIDs) of the skin such as atopic dermatitis, alopecia areata and vitiligo, ¹ , ² and their effectiveness has been confirmed by several meta‐analyses. ³ , ⁴ , ⁵ , ⁶ , ⁷ They provide a rapid and clinical improvement in multiple clinical domains of IMIDs of the skin by blocking multiple intracellular cytokine pathways that trigger inflammation and disease activity. ¹

Despite their efficacy, safety concerns remain regarding the risk of infections associated with JAK–STAT inhibitors. The JAK–STAT pathway plays a crucial role in antiviral and antibacterial defence, and its inhibition may predispose patients to infections. ⁸ A recent pharmacovigilance analysis based on the FDA Adverse Event Reporting System suggests an overall increased risk of infection with several JAK inhibitors, including herpes zoster, influenza and COVID‐19. ⁹

Previous meta‐analyses in dermatology indications have mainly focused on only pre‐specified infection types, such as upper respiratory infection, nasopharyngitis, serious infection and folliculitis, ¹⁰ , ¹¹ , ¹² , ¹³ and no analysis has comprehensively evaluated all types of reported infections separately in skin diseases. Furthermore, previous studies have not systematically compared JAK–STAT inhibitors with active comparators and have not specifically evaluated topical JAK–STAT inhibitors. To date, no meta‐analysis has provided such an integrated and in‐depth assessment of the risk of infection in this therapeutic class.

Therefore, our study aimed to conduct the first comprehensive systematic review and meta‐analysis of randomized controlled trials (RCTs) evaluating the infection risks associated with systemic and topical JAK–STAT inhibitors in IMIDs of the skin.

METHODS

This study was conducted as part of the System Education Program at Semmelweis University ¹⁴ and within the Translational Medicine TM Cycle Framework of Academia Europaea. ¹⁵

This systematic review and meta‐analysis was performed in accordance with the instructions in the Cochrane Handbook ¹⁶ and reported following PRISMA 2020 guidelines. ¹⁷ The protocol was prospectively registered with PROSPERO (CRD42024615839).

Eligibility criteria

This study included only RCTs that compared a systemic or topical JAK–STATi with a placebo and/or an active comparator (non‐JAK–STATi), and investigated the safety and reported infection‐related adverse events in patients with alopecia, psoriasis, vitiligo, atopic dermatitis or hidradenitis suppurativa. We did not apply any restriction based on the type of infection to ensure a comprehensive assessment of infection risk. Pooled analyses and post hoc analyses of RCTs were excluded, and the original study was included. The trials were included in the synthesis only up to the time point of treatment change or crossover, and only if the available outcome data were still comparable with the initial placebo or active‐comparator group.

Search strategy and selection process

The systematic search was conducted in three databases (MEDLINE via PubMed, EMBASE and Cochrane Library) on 19 November 2024. No special filters, settings or restrictions were made. The detailed search strategy is presented in the Supporting Information Material, including the number of hits in each database.

Upon completing the systematic search, the retrieved articles were imported into EndNote (version 21, Clarivate Analytics, Philadelphia, PA, USA). ¹⁸ Duplicates were automatically and manually removed within EndNote. The selection process was performed independently by two reviewers (M.K. and M.V.K.), first by reviewing the titles and abstracts and then by assessing the full text using Rayyan Systems software (Cambridge, MA, USA). ¹⁹ A third reviewer (L.G.) resolved disagreements.

Data collection and synthesis

A standardized data collection sheet based on a consensus of methodological and clinical experts was used to extract the data. Two independent reviewers (M.K. and B.N.) extracted the following data from eligible articles: first author's last name, publication year, disease, number of patients, study duration, population characteristics, intervention, comparators, type of adverse event and number of adverse events.

Infectious adverse events were not pre‐specified and not restricted by type. This meta‐analysis included all infection‐related outcomes that were reported in at least three RCTs. These outcomes were: upper respiratory tract infection, nasopharyngitis, pharyngitis, sinusitis, influenza, bronchitis, COVID‐19, pneumonia, oral herpes, herpes zoster, herpes simplex, genital herpes, eczema herpeticum, urinary tract infection, folliculitis, gastroenteritis, wound infection, opportunistic infection, serious infection, candida and tinea infection. Serious infections were analysed as reported in the RCTs. Across studies, these definitions were broadly consistent with standard criteria for serious adverse events, including infections that result in death, life‐threatening conditions or hospitalization or parenteral antimicrobial treatment. However, minor variations in definitions and reporting may have been present across individual studies.

We evaluated the risk of bias using the Risk of Bias Tool 2 (RoB 2). ²⁰ It was conducted by two independent reviewers (M.K. and B.N.), and any disagreements were resolved by a third independent reviewer (L.G.). Publication bias was assessed by visual inspection of the funnel plots. The quality of evidence was evaluated using the GRADE‐Pro tool as recommended by the Cochrane Collaboration. ²¹

Statistical analysis

As we assumed considerable between‐study heterogeneity in all cases, a random‐effects model was used to pool effect sizes. In the case of dichotomous outcomes, the risk ratio (RR) with 95% confidence interval (CI) was used for the effect size measure.

To calculate the study risk ratios and the pooled risk ratio, the total number of patients and those with the event of interest in each group separately (referred to as ‘raw data’) were extracted or calculated from the studies where available. We reported the results as the risk of the event of interest in the experimental group versus the risk of the event of interest in the control group.

Results were considered statistically significant if the pooled CI did not contain the null value. We summarized the findings related to the meta‐analysis on forest plots. Absolute between‐study heterogeneity was expressed by tau, and relative between‐study heterogeneity was described by Higgins and Thompson's I ² statistics. ²² Where applicable and the study number was large enough and not too heterogeneous, we reported the prediction intervals (i.e., the expected range of true effects of future studies) of results too.

All analyses were performed in R. ²³ Further details are provided in the Supporting Information Material.

RESULTS

Search and selection

The systematic search yielded a total of 5065 records. After selecting the title, abstract and full text, 69 articles met the inclusion criteria. No additional study was identified by citation search. A total of 69 articles, ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ , ⁵¹ , ⁵² , ⁵³ , ⁵⁴ , ⁵⁵ , ⁵⁶ , ⁵⁷ , ⁵⁸ , ⁵⁹ , ⁶⁰ , ⁶¹ , ⁶² , ⁶³ , ⁶⁴ , ⁶⁵ , ⁶⁶ , ⁶⁷ , ⁶⁸ , ⁶⁹ , ⁷⁰ , ⁷¹ , ⁷² , ⁷³ , ⁷⁴ , ⁷⁵ , ⁷⁶ , ⁷⁷ , ⁷⁸ , ⁷⁹ , ⁸⁰ , ⁸¹ , ⁸² , ⁸³ , ⁸⁴ , ⁸⁵ , ⁸⁶ , ⁸⁷ , ⁸⁸ , ⁸⁹ , ⁹⁰ , ⁹¹ , ⁹² , ⁹³ including the results of 74 RCTs, were included in the systematic review and meta‐analysis. The selection process is detailed in Figure 1. A total of 68 RCTs ²⁴ , ²⁵ , ²⁶ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁵¹ , ⁵² , ⁵³ , ⁵⁴ , ⁵⁵ , ⁵⁶ , ⁵⁷ , ⁵⁸ , ⁵⁹ , ⁶⁰ , ⁶¹ , ⁶² , ⁶³ , ⁶⁴ , ⁶⁶ , ⁶⁷ , ⁶⁸ , ⁶⁹ , ⁷⁰ , ⁷¹ , ⁷² , ⁷³ , ⁷⁴ , ⁷⁶ , ⁷⁷ , ⁷⁸ , ⁷⁹ , ⁸⁰ , ⁸¹ , ⁸² , ⁸³ , ⁸⁴ , ⁸⁵ , ⁸⁶ , ⁸⁸ , ⁸⁹ , ⁹⁰ , ⁹¹ , ⁹² , ⁹³ were eligible for quantitative synthesis. One RCT ⁷⁵ was included only in the qualitative analysis. Five multi‐arm RCTs ²⁷ , ⁴⁹ , ⁵⁰ , ⁶⁵ , ⁸⁷ were analysed in both quantitative and qualitative synthesis, as some active comparator arms (apremilast, zimlovisertib, tacrolimus, triamcinolone) were not suitable for quantitative analysis due to an insufficient number of identical comparators.

PRISMA 2020 flow chart representing the study selection process.

Basic characteristics of included studies

Baseline characteristics of the included RCTs are detailed in Table S1.

Quantitative analysis

A comprehensive overview of all findings is provided in Table 1 and Tables S2–S6. Significant results have been highlighted separately in Table 1. All outcomes in each table are sorted in descending order based on the pooled risk ratio (RR), which reflects the correlation between the intervention and each endpoint.

TABLE 1.

Summary of statistically significant results.

Outcomes	Number of results (n)	JAK‐STATi events (n)	JAK‐STATi Total (n)	Prevalence on JAK‐STATi (%)	Placebo events (n)	Placebo total (n)	Prevalence on placebo (%)	Relative risk	95% confidence interval
Oral herpes	11	78	4179	1.87	7	1364	0.51	2.75	1.93–3.92
Influenza	11	90	3746	2.40	13	1262	1.03	2.12	1.03–4.36
Bronchitis	11	66	3134	2.11	7	904	0.77	2.03	1.43–2.88
Herpes zoster	42	149	13072	1.14	17	4832	0.35	1.67	1.29–2.15
Pharyngitis	7	27	1696	1.59	5	500	1	1.44	1.06–1.96
Upper respiratory tract infection	51	957	15166	6.31	291	5870	4.96	1.25	1.12–1.39

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Abbreviations: JAK‐STATi, Janus kinase–signal transducer and activation of transcription inhibitor; n = number.

To our knowledge, this is the first meta‐analysis to investigate the prevalence of influenza in patients treated with JAK–STAT inhibitors in IMIDs of the skin, revealing a significantly increased risk compared to the placebo group. Influenza was assessed in 11 studies, involving 3746 people exposed to JAK–STATi and 1262 people exposed to a placebo. JAK–STAT inhibitors were associated with a significantly higher risk of influenza compared with a placebo (RR = 2.12, 95% CI 1.03–4.36) (Figure 2). Upon subgroup analysis based on diseases, we identified that risk increases dominantly in patients with atopic dermatitis with a risk ratio of 3.22 (95% CI, 2.03–5.10) (see Figure S1).

Risk of influenza associated with JAK‐STAT inhibitor treatment compared with placebo. RR, risk ratio; JAK‐STATi, Janus kinase–signal transducer and activation of transcription inhibitor; CI, confidence interval.

We observed that other respiratory infections also showed a significantly increased risk in the JAK–STATi group. Bronchitis was assessed in 11 studies, including 3134 patients receiving JAK–STAT inhibitors and 904 patients receiving a placebo, and was associated with a significantly increased risk compared with a placebo (RR = 2.03, 95% CI 1.43–2.88) (see Figure S2). Similarly, pharyngitis, assessed in 7 trials, occurred more often among patients receiving JAK–STAT inhibitors than a placebo (RR = 1.44, 95% CI 1.06–1.96) (see Figure S3). We also observed a significant increase in upper respiratory tract infections among patients treated with JAK–STATi compared with a placebo (RR = 1.25, 95% CI 1.12–1.39) (see Figure S4). Subgroup analysis based on diseases showed a significantly higher risk ratio for patients with atopic dermatitis (RR = 1.26, 95% CI 1.08–1.47) and for patients with psoriasis (RR = 1.62, 95% CI 1.21–2.17) (see Figure S5).

There was no significant increased risk with JAK–STAT inhibitors for nasopharyngitis (RR = 1.08, 95% CI 0.97–1.20), sinusitis (RR = 1.14, 95% CI 0.71–1.82), COVID‐19 (RR = 1.09, 95% CI 0.78–1.52) or pneumonia (RR = 0.46, 95% CI 0.07–3.14) (see Figures S6–S9).

Among herpetic infections, oral herpes showed the highest relative risk compared with a placebo (RR = 2.75, 95% CI 1.93–3.92) (see Figure S10). Subgroup analysis showed that the risk ratio was particularly high in patients with atopic dermatitis (RR = 3.29, 95% CI 2.30–4.71) (see Figure S11). This outcome was reported as oral herpes without further specification of the clinical subtype. Herpes zoster was assessed in 42 studies, including 13,072 patients receiving JAK–STAT inhibitors and 4832 patients receiving a placebo. The risk of herpes zoster was significantly higher among patients exposed to JAK–STAT inhibitors (RR = 1.67, 95% CI 1.29–2.15) (Figure 3). Subgroup analysis based on diseases demonstrated a significantly higher risk ratio for herpes zoster in patients with atopic dermatitis compared with a placebo (RR = 2.00, 95% CI 1.34–2.99) (see Figure S12), and this risk increased further compared with the dupilumab in atopic patients (RR = 3.52, 95% CI 1.82–6.81) (see Figure S13). Furthermore, a significantly increased risk was observed in patients with psoriatic arthritis (RR = 1.79, 95% CI 1.17–2.75) (see Figure S12).

Risk of herpes zoster associated with JAK‐STAT inhibitor treatment compared with placebo. RR, risk ratio; JAK‐STATi, Janus kinase–signal transducer and activation of transcription inhibitor; CI, confidence interval.

Neither herpes simplex, genital herpes nor eczema herpeticum infections showed a significant association with the use of JAK–STAT inhibitors (RR = 1.04, 95% CI 0.70–1.55; RR = 0.95, 95% CI 0.27–3.31; RR = 0.64, 95% CI 0.32–1.29, respectively) (see Figures S14–S16).

There were no significant differences between the JAK–STAT and placebo groups for other infection types in patients treated with JAK–STATi, including gastroenteritis (RR = 1.14, 95% CI 0.52–2.50), folliculitis (RR = 1.05, 95% CI 0.56–1.98), urinary tract infection (RR = 1.02, 95% CI 0.81–1.28) and opportunistic infection (RR = 0.70, 95% CI 0.48–1.03) (see Figures S17–S20).

No significant increased risk was observed for fungal infections in patients treated with JAK–STATi, including candida infection (RR = 0.94, 95% CI 0.27–3.27) and tinea infection (RR = 0.56, 95% CI 0.21–1.46) (see Figures S21 and S22).

Serious infections were assessed in 34 studies, including 11,040 patients receiving JAK–STAT inhibitors and 4338 patients receiving a placebo. No statistically significant difference in the risk of serious infection was observed between the two groups (RR = 1.09, 95% CI 0.80–1.47) (see Figure S23).

No significant differences in the risk of infections were observed between JAK–STAT inhibitors and dupilumab or TNF inhibitors, except for the previously mentioned increased risk of herpes zoster in patients with atopic dermatitis compared with dupilumab (see Tables S3 and S4, Figures S24–S31).

Topical JAK–STAT inhibitors did not show a significantly increased risk of infection compared to a vehicle (see Table S5, Figures S32–S37).

Qualitative analysis

The results of the studies not suitable for statistical synthesis are summarized in Table S6. These included studies comparing JAK–STAT inhibitors with active comparators, such as apremilast, azathioprine and zimlovisertib. No significant differences in the risk of infections were observed in the trials except for one (Armstrong et al. ²⁷ ) wheren upper respiratory tract infections were significantly increased in the JAK–STAT group compared with apremilast (RR = 3.54, 95% CI 1.07–11.71).

In addition, topical JAK–STAT inhibitors using active comparators such as tacrolimus and triamcinolone were analysed qualitatively. No significant differences in the risk of infection were observed.

Risk of bias assessment

When assessing the risk of bias, the majority of RCTs were classified as low risk, some were classified as medium risk and none were classified as high risk. A detailed risk of bias assessment can be found in the Tables S7 and S8.

Publication bias

The funnel plots for our outcomes did not show evidence of publication bias (see Figures S38–S72).

Certainty of evidence

The certainty assessment is described in Tables S9–S12.

DISCUSSION

To our knowledge, this meta‐analysis is the most comprehensive study to evaluate the risk of infections associated with JAK–STAT inhibitors in IMIDs of the skin, analysing more than 20 types of infections. In addition to confirming previously known infection risks, it also provides new insights by identifying and quantifying the risk of specific infections, such as influenza, which have not been systematically evaluated in previous studies. Another novelty is that we examined the risk of infection not only in comparison with placebos but also in comparison with other active comparators.

Atopic dermatitis is itself highly susceptible to skin infection and systemic infection like respiratory viral infections, possibly due to underlying immune dysregulations and defects in the skin barrier. ⁹⁴ , ⁹⁵ , ⁹⁶ The use of JAK–STAT inhibitors in atopic dermatitis may further impair the antiviral immune response, as JAK–STAT signalling is critical for interferon‐mediated antiviral protection. ⁹⁷ , ⁹⁸ As the JAK–STAT pathway plays a central role in antiviral defence, its inhibition may also contribute to the increased susceptibility to herpes zoster observed in patients receiving these agents. ⁹⁹ Consistent with this mechanism, this is the first meta‐analysis to show an increased risk of influenza in patients treated with JAK–STAT inhibitors compared to placebos in IMIDs of the skin. This is particularly relevant for elderly patients, who are already more susceptible to influenza infection and are at greater risk of developing serious complications. ¹⁰⁰ , ¹⁰¹ Advanced age is a well‐known risk factor for infection, which is partly attributable to the aging of the immune system, which impairs the functioning of both the innate and adaptive immune responses. ¹⁰² , ¹⁰³ , ¹⁰⁴ In addition, a higher burden of comorbidities and concurrent treatments further increase older adults' susceptibility to infection. ¹⁰⁵ , ¹⁰⁶ , ¹⁰⁷

The use of JAK–STAT inhibitors in elderly patients with atopic eczema should be carefully considered, weighing the benefits of disease control against the increased risk of influenza and the potential serious complications. Consideration of annual influenza vaccination and close surveillance is recommended for this high‐risk group. ¹⁰⁸

Our analysis did not confirm a significant risk of COVID‐19 infection among patients treated with JAK–STAT inhibitors, but this result should be interpreted with caution. JAK–STAT inhibitors have been investigated as therapeutic agents in severe COVID‐19 cases to alleviate cytokine‐induced hyperinflammation. ¹⁰⁹ , ¹¹⁰ While such immunomodulatory effects may be beneficial in acute cytokine storms, these agents may continue to influence antiviral defence mechanisms during chronic treatment of inflammatory diseases. Real‐world data are needed to clarify the long‐term relationship between JAK–STAT inhibition and COVID‐19 susceptibility.

Recent meta‐analyses and large cohort studies have consistently shown that JAK–STAT inhibitors are associated with an increased risk of respiratory tract infections in dermatological indications. ¹⁰ , ¹² Specifically, upper respiratory infections and pharyngitis were common adverse events in patients receiving JAK inhibitors, with similar risk ratios to those found in our analysis. These infections are typically mild to moderate in severity and rarely lead to treatment interruption or serious side effects. The specific infectious agents responsible for these respiratory infections were not reported in the included studies; therefore, pathogen‐specific analysis was not feasible.

Our meta‐analysis is the first to show a significantly increased risk of bronchitis associated with JAK–STAT inhibitor treatment. This new finding expands the current knowledge of respiratory adverse events associated with JAK–STAT inhibition. Although most bronchitis cases were mild, this observation emphasizes the importance of clinical vigilance, especially in patients with pre‐existing lung disease or those receiving concomitant immunosuppressive therapy. ¹¹¹

The identification of a previously unreported increased risk of oral herpes among patients treated with JAK–STAT inhibitors is significant because it adds to the current knowledge of JAK–STAT‐related viral susceptibility and class‐specific safety concerns in dermatological indications. Previous meta‐analyses have focused on herpes zoster and broader infection risks but have not quantified oral herpes as an outcome. ¹⁰ , ¹² , ¹¹² This finding highlights the importance of patient education regarding possible herpetic infections, particularly in patients with atopic dermatitis with an elevated basal infection risk. It supports the need for individualized risk assessment and preventive strategies, as recommended by the American Academy of Allergy, Asthma and Immunology. ¹¹³

Meta‐analyses and large cohort studies have shown that JAK–STAT inhibitors are associated with an increased risk of herpes zoster compared to placebos and dupilumab. ¹⁰ , ¹² , ¹¹² , ¹¹⁴ Our results are consistent with these observations.

They should also be interpreted in the context of recent real‐world and long‐term safety observations. In the prospective BioDay registry, patients with moderate‐to‐severe atopic dermatitis who received JAK inhibitors had higher infection rates than those on biologics, especially herpes infections. ¹¹⁵ In addition, a 6‐year safety analysis of upadacitinib for the treatment of atopic dermatitis showed that the incidence of infections varied significantly by dose. ¹¹⁶ At the 30 mg dose, there was an increased incidence of herpes zoster, as well as a slight increase in the number of serious and opportunistic infections. These safety data further reinforce the clinical importance of stratifying infection risk within the JAK inhibitor class.

Together, our findings and these data further reinforce the importance of herpes zoster vaccination prior to initiating JAK–STAT inhibitor therapy, in line with American Academy of Dermatology guidelines, particularly in adults aged 50 years or older and in immunocompromised patients with atopic dermatitis, ¹¹⁷ and supported by European recommendations, including a position statement of the Italian Society of Dermatology and Venereology. ¹¹⁸ In high‐risk populations, dupilumab should be considered as an alternative treatment option for atopic dermatitis, given its more favourable herpetic viral infection profile.

A previous meta‐analysis of 19 RCTs in dermatologic indications reported modest increases in folliculitis (RR = 1.68, 95% CI 1.03–2.77) and nasopharyngitis (RR = 1.36, 95% CI 1.15–1.61). ¹³ We observed similar trends, but these were not significant in our analysis.

Although JAK–STAT inhibitors can affect immune cells involved in antifungal defence, including Th1, Th17 and phagocyte activation, leading to a decrease in neutrophil activation and cytokine production, ¹¹⁹ a previous report has suggested a possible association with fungal infections. ⁹⁶ However, our meta‐analysis did not find a significant increase in candida or tinea infection risk among patients receiving JAK‐STAT inhibitors.

The phase III ORAL clinical study found that patients treated with JAK inhibitors for rheumatoid arthritis may have a higher risk of serious infections. ¹²⁰ In contrast, our analysis found no significant risk of serious infection compared to a placebo, in line with previous meta‐analysis. ¹⁰ , ¹¹ , ¹² Compared to previous meta‐analyses, our analysis also included studies with active comparators, such as dupilumab and TNF inhibitors, and similarly found no significant difference in the risk of serious infection between JAK–STAT inhibitors and active comparators. The ORAL study included patients aged 50 years or older with rheumatoid arthritis who had at least one additional cardiovascular risk factor, representing a higher risk population than those enrolled in dermatology clinical trials.

Compared to the ORAL study, the patients included in our meta‐analysis were generally younger, had fewer comorbidities and some of the RCTs included children. These demographic differences, as well as the lack of concomitant methotrexate use, may contribute to the lower incidence of serious infections in our analysis. In addition, the median follow‐up period for ORAL was approximately 4 years. In contrast, the treatment periods in most included dermatological studies were short, and only a few studies lasted 52 weeks.

Consistent with a previous pharmacokinetic study, topical JAK‐STAT inhibitors did not increase the risk of infection compared to a vehicle, supporting a favourable systemic infection safety profile with the use recommended in the guidelines. ¹²¹ , ¹²²

Strengths

This study has several important strengths. To our knowledge, it is the most comprehensive meta‐analysis to date evaluating the risk of JAK‐STAT‐related infections in IMIDs of the skin, assessing more than 20 different types of infections. The analysis integrates evidence from placebo‐controlled and active comparative trials—including dupilumab and TNF inhibitors—and distinguishes between systemic and topical therapies. Furthermore, by synthesizing data from 74 RCTs involving more than 29,000 patients, this study provides the most statistically robust safety assessment available and identifies previously unreported infection types, such as increased risk of influenza, bronchitis and oral herpes, while confirming no increased risk of serious fungal or opportunistic infections.

Limitations

This study has several limitations. The majority of RCTs included had a short median follow‐up period, and only a few extended over a longer period. Therefore, our results mainly reflect short‐term safety outcomes, and long‐term infectious risks remain uncertain. In addition, the study populations were highly selected, consisting predominantly of middle‐aged patients with few comorbidities, which may limit the generalizability of our results to real‐world or elderly populations. Furthermore, although infection results were consistently reported, definitions and diagnostic criteria may not have been entirely consistent across studies. The assessment of some infections may have been investigator‐dependent.

Furthermore, diagnostic methods were not always consistent across studies, with some studies relying solely on clinical presentation, while others used specific tests for confirmation. In addition, the classification of certain infections was limited by the original reporting of the included RCTs; for example, ‘oral herpes’ was not further specified, which may affect the precision of outcome definitions.

Implication for practice and research

Although the prevalence of infections was low, this likely reflects the short follow‐up period. Even a modest increase in the risk of infection may have important clinical consequences in real‐life settings, where patients often receive long‐term therapy and may have additional risk factors, such as advanced age, comorbidities or concomitant immunosuppressive treatment.

Integrating evidence into clinical practice is a core principle of the Academia Europaea Translational Medicine framework. ¹²³ , ¹²⁴

Our findings highlight the importance of patient education, as well as assessing and preventing the risk of infection, prior to initiating JAK–STAT inhibitor therapy, particularly in patients with atopic dermatitis. Vaccination against influenza and herpes zoster should be considered before initiating treatment in high‐risk populations, as should annual re‐evaluation. In high‐risk atopic populations, such as the elderly or immunocompromised patients, dupilumab may be a safer alternative due to its lower herpes infection risk profile.

Further large‐scale, real‐world, long‐term studies are needed to clarify the long‐term infection risk profile of JAK–STAT inhibitors outside controlled trial settings.

CONCLUSIONS

This meta‐analysis supports the safe use of JAK‐STAT inhibitors in dermatological indications. However, clinicians should be aware of a modest increase in infection risk, especially in patients with atopic dermatitis. These findings suggest that herpes zoster and influenza vaccination should be considered before starting the treatment in a high‐risk population.

AUTHOR CONTRIBUTIONS

Máté Krebs: Conceptualization, project administration, methodology, formal analysis and writing—original draft. Lili Gulyás: Conceptualization, formal analysis, visualization, writing—review and editing. Karen Krisztina Fazekas: Methodology, formal analysis, validation, visualization and writing—review and editing. Benedek Nagy: Data curation and writing—review and editing. Mária Veronika Kolonics: Conceptualization, data curation and writing—review and editing. Fanni Adél Meznerics: Conceptualization, methodology, supervision and writing—review and editing. Norbert Kiss: Conceptualization, methodology, supervision and writing—review and editing. András Bánvölgyi: Conceptualization, methodology, supervision and writing—review and editing. Péter Hegyi.: Conceptualization, methodology, supervision and writing—review and editing. Péter Holló: Conceptualization, methodology, supervision and writing—original draft. Lajos Vince Kemény: Conceptualization, methodology, supervision and writing—original draft. All authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing or revision of the manuscript.

FUNDING INFORMATION

The authors have nothing to report.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

ETHICAL APPROVAL

No ethical approval was required for this systematic review with meta‐analysis, as all data were already published in peer‐reviewed journals.

ETHICS STATEMENT

No patients were involved in the design, conducting or interpretation of our study.

Supporting information

Figures S1–S72.

Tables S1–S13.

JDV-40-1662-s001.docx^{(3MB, docx)}

Data S2.

JDV-40-1662-s002.docx^{(269.3KB, docx)}

Krebs M, Gulyás L, Fazekas KK, Nagy B, Kolonics MV, Meznerics FA, et al. Large‐scale meta‐analysis of infection risk with JAK–STAT inhibitors in 29,000 patients. J Eur Acad Dermatol Venereol. 2026;40:1662–1674. 10.1111/jdv.70508

Péter Holló and Lajos Vince Kemény share last authorship.

Contributor Information

Péter Holló, Email: hollo.peter@semmelweis.hu.

Lajos Vince Kemény, Email: kemeny.lajos@semmelweis.hu.

DATA AVAILABILITY STATEMENT

The datasets used in this study can be found in the full‐text articles included in the systematic review and meta‐analysis.

REFERENCES

1. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10:2342. [DOI] [PMC free article] [PubMed] [Google Scholar]
2. Ryguła I, Pikiewicz W, Kaminiów K. Novel Janus kinase inhibitors in the treatment of dermatologic conditions. Molecules. 2023;28(24):8064. [DOI] [PMC free article] [PubMed] [Google Scholar]
3. Zhang L, Wang L, Jiang X. The efficacy of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and network meta‐analysis. Dermatol Ther. 2021;34(5):e15098. [DOI] [PubMed] [Google Scholar]
4. Yang F, Lu C, Wang Y, Liu H, Leng X, Zeng X. Efficacy and safety of Janus kinase inhibitors in patients with psoriasis and psoriatic arthritis: a systematic review and meta‐analysis. Clin Rheumatol. 2023;42(6):1593–1605. [DOI] [PubMed] [Google Scholar]
5. Liu M, Gao Y, Yuan Y, Yang K, Shen C, Wang J, et al. Janus kinase inhibitors for alopecia areata: a systematic review and meta‐analysis. JAMA Netw Open. 2023;6(6):e2320351‐e. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Mohammed AA, Lengyel AS, Meznerics FA, Szondy I, Walter A, Szabó B, et al. Efficacy and safety of JAK inhibitors in the Management of vitiligo: a systematic review and meta‐analysis. Dermatol Ther (Heidelb). 2025;15(7):1657–1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
7. Garg A, Cohn E, Midgette B, Frasier K, Strunk A. Efficacy and safety of medical interventions for moderate to severe hidradenitis Suppurativa: a living systematic review and network meta‐analysis. JAMA Dermatol. 2025;161(9):931–940. [DOI] [PMC free article] [PubMed] [Google Scholar]
8. Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak‐STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–384. [DOI] [PMC free article] [PubMed] [Google Scholar]
9. Altınöz Güney C, Koç HA. Investigation of infection risk associated with Janus kinase inhibitors: a pharmacovigilance analysis using the Food and Drug Administration's adverse event reporting system database. Clin Exp Dermatol. 2025;51:226–235. [DOI] [PubMed] [Google Scholar]
10. Yoon S, Kim K, Shin K, Kim HS, Kim B, Kim MB, et al. The safety of systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta‐analysis of randomized controlled trials. J Eur Acad Dermatol Venereol. 2024;38(1):52–61. [DOI] [PubMed] [Google Scholar]
11. Su X, Ou Y, Ruan S, Lv X, Qin K, Mao J, et al. Risk of serious infection with JAK inhibitors in immune‐mediated inflammatory skin diseases: a meta‐analysis of randomized clinical trials. J Dermatol Treat. 2025;36(1):2474507. [DOI] [PubMed] [Google Scholar]
12. Ireland PA, Verheyden M, Jansson N, Sebaratnam D, Sullivan J. Infection risk with JAK inhibitors in dermatoses: a meta‐analysis. Int J Dermatol. 2025;64(1):24–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
13. Isufi D, Jensen MB, Loft N, Skov L, Elberling J, Alinaghi F. Risk of infections during treatment with oral Janus kinase inhibitors in randomized placebo‐controlled trials: a systematic review and meta‐analysis. JAAD Int. 2025;18:106–116. [DOI] [PMC free article] [PubMed] [Google Scholar]
14. Hegyi P, Varró A. Systems education can train the next generation of scientists and clinicians. Nat Med. 2024;30(12):3399–3400. [DOI] [PubMed] [Google Scholar]
15. Hegyi P, Petersen OH, Holgate S, Erőss B, Garami A, Szakács Z, et al. Academia Europaea position paper on translational medicine: the cycle model for translating scientific results into community benefits. J Clin Med. 2020;9(5):1532. [DOI] [PMC free article] [PubMed] [Google Scholar]
16. Cochrane . Cochrane handbook for systematic reviews of interventions. Cochrane; 2024. Available from: https://www.cochrane.org/handbook. [Google Scholar]
17. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
18. Bramer WM, Giustini D, de Jonge GB, Holland L, Bekhuis T. De‐duplication of database search results for systematic reviews in EndNote. J Med Libr Assoc. 2016;104(3):240–243. [DOI] [PMC free article] [PubMed] [Google Scholar]
19. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan‐a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. [DOI] [PMC free article] [PubMed] [Google Scholar]
20. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. [DOI] [PubMed] [Google Scholar]
21. GDT G . GRADEpro guideline development tool. McMaster University and Evidence Prime; 2023. [Google Scholar]
22. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. 2002;21(11):1539–1558. [DOI] [PubMed] [Google Scholar]
23. Team RC . R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2024. [Google Scholar]
24. Alavi A, Hamzavi I, Brown K, Santos LL, Zhu Z, Liu H, et al. Janus kinase 1 inhibitor INCB054707 for patients with moderate‐to‐severe hidradenitis suppurativa: results from two phase II studies. Br J Dermatol. 2022;186(5):803–813. [DOI] [PMC free article] [PubMed] [Google Scholar]
25. Anderson S, Cavaletti G, Hood LJ, Polydefkis M, Herrmann DN, Rance G, et al. A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata. Pharmacol Res Perspect. 2024;12(4):e1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
26. Armstrong AW, Gooderham M, Lynde C, Maari C, Forman S, Green L, et al. Tyrosine kinase 2 inhibition with zasocitinib (TAK‐279) in psoriasis: a randomized clinical trial. JAMA Dermatol. 2024;160(10):1066–1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
27. Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52‐week, randomized, double‐blinded, placebo‐controlled phase 3 POETYK PSO‐1 trial. J Am Acad Dermatol. 2023;88(1):29–39. [DOI] [PubMed] [Google Scholar]
28. Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib versus etanercept or placebo in moderate‐to‐severe chronic plaque psoriasis: a phase 3 randomised non‐inferiority trial. Lancet. 2015;386(9993):552–561. [DOI] [PubMed] [Google Scholar]
29. Bieber T, Reich K, Paul C, Tsunemi Y, Augustin M, Lacour JP, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate‐to‐severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo‐controlled, phase III clinical trial (BREEZE‐AD4). Br J Dermatol. 2022;187(3):338–352. [DOI] [PubMed] [Google Scholar]
30. Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101–1112. [DOI] [PubMed] [Google Scholar]
31. Bissonnette R, Iversen L, Sofen H, Griffiths CE, Foley P, Romiti R, et al. Tofacitinib withdrawal and retreatment in moderate‐to‐severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172(5):1395–1406. [DOI] [PubMed] [Google Scholar]
32. Bissonnette R, Luchi M, Fidelus‐Gort R, Jackson S, Zhang H, Flores R, et al. A randomized, double‐blind, placebo‐controlled, dose‐escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis. J Dermatolog Treat. 2016;27(4):332–338. [DOI] [PubMed] [Google Scholar]
33. Bissonnette R, Maari C, Forman S, Bhatia N, Lee M, Fowler J, et al. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate‐to‐severe atopic dermatitis: results from a randomized double‐blind placebo‐controlled study. Br J Dermatol. 2019;181(4):733–742. [DOI] [PMC free article] [PubMed] [Google Scholar]
34. Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–911. [DOI] [PubMed] [Google Scholar]
35. Blauvelt A, Silverberg JI, Lynde CW, Bieber T, Eisman S, Zdybski J, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate‐to‐severe atopic dermatitis: results from the JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN phase 3 trial. J Am Acad Dermatol. 2022;86(1):104–112. [DOI] [PubMed] [Google Scholar]
36. Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin‐Weller M, Barbarot S, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate‐to‐severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157(9):1047–1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
37. Changelian P, Xu C, Mnich S, Hope H, Kostecki K, Hirsch J, et al. ATI‐1777, a topical Jak1/3 inhibitor, may benefit atopic dermatitis without systemic drug exposure: results from preclinical development and phase 2a randomized control study ATI‐1777‐AD‐201. JID Innov. 2024;4(2):100251. [DOI] [PMC free article] [PubMed] [Google Scholar]
38. David E, Shokrian N, Del Duca E, Meariman M, Dubin C, Hawkins K, et al. A phase 2a trial of brepocitinib for cicatricial alopecia. J Am Acad Dermatol. 2025;92(3):427–434. [DOI] [PubMed] [Google Scholar]
39. Eichenfield LF, Flohr C, Sidbury R, Siegfried E, Szalai Z, Galus R, et al. Efficacy and safety of abrocitinib in combination with topical therapy in adolescents with moderate‐to‐severe atopic dermatitis: the JADE TEEN randomized clinical trial. JAMA Dermatol. 2021;157(10):1165–1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
40. Ezzedine K, Peeva E, Yamaguchi Y, Cox LA, Banerjee A, Han G, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88(2):395–403. [DOI] [PubMed] [Google Scholar]
41. Forman SB, Pariser DM, Poulin Y, Vincent MS, Gilbert SA, Kieras EM, et al. TYK2/JAK1 inhibitor PF‐06700841 in patients with plaque psoriasis: phase IIa, randomized, double‐blind, placebo‐controlled trial. J Invest Dermatol. 2020;140(12):2359–2370.e5. [DOI] [PubMed] [Google Scholar]
42. Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377(16):1525–1536. [DOI] [PubMed] [Google Scholar]
43. Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of Oral Janus kinase 1 inhibitor Abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. JAMA Dermatol. 2019;155(12):1371–1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
44. Guttman‐Yassky E, Facheris P, Gomez‐Arias PJ, Del Duca E, Da Rosa JC, Weidinger S, et al. Effect of abrocitinib on skin biomarkers in patients with moderate‐to‐severe atopic dermatitis. Allergy. 2024;79(5):1258–1270. [DOI] [PubMed] [Google Scholar]
45. Guttman‐Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate‐to‐severe atopic dermatitis: a phase 2 parallel, double‐blinded, randomized placebo‐controlled multiple‐dose study. J Am Acad Dermatol. 2019;80(4):913–921.e9. [DOI] [PubMed] [Google Scholar]
46. Guttman‐Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, et al. Once‐daily upadacitinib versus placebo in adolescents and adults with moderate‐to‐severe atopic dermatitis (measure up 1 and measure up 2): results from two replicate double‐blind, randomised controlled phase 3 trials. Lancet. 2021;397(10290):2151–2168. [DOI] [PubMed] [Google Scholar]
47. Guttman‐Yassky E, Thaçi D, Pangan AL, Hong HC, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16‐week results from a randomized, placebo‐controlled trial. J Allergy Clin Immunol. 2020;145(3):877–884. [DOI] [PubMed] [Google Scholar]
48. Katoh N, Ohya Y, Murota H, Ikeda M, Hu X, Ikeda K, et al. Safety and efficacy of upadacitinib for atopic dermatitis in Japan: 2‐year interim results from the phase 3 rising up study. Dermatol Ther (Heidelb). 2023;13(1):221–234. [DOI] [PMC free article] [PubMed] [Google Scholar]
49. Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572–582. [DOI] [PubMed] [Google Scholar]
50. Kimball AB, Peeva E, Forman S, Moiin A, Khattri S, Porter ML, et al. Brepocitinib, zimlovisertib, and ropsacitinib in hidradenitis suppurativa. NEJM Evid. 2024;3(3):EVIDoa2300155. [DOI] [PubMed] [Google Scholar]
51. King B, Guttman‐Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, et al. A phase 2a randomized, placebo‐controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24‐week results. J Am Acad Dermatol. 2021;85(2):379–387. [DOI] [PubMed] [Google Scholar]
52. King B, Mesinkovska N, Mirmirani P, Bruce S, Kempers S, Guttman‐Yassky E, et al. Phase 2 randomized, dose‐ranging trial of CTP‐543, a selective Janus kinase inhibitor, in moderate‐to‐severe alopecia areata. J Am Acad Dermatol. 2022;87(2):306–313. [DOI] [PubMed] [Google Scholar]
53. King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687–1699. [DOI] [PubMed] [Google Scholar]
54. King B, Senna MM, Mesinkovska NA, Lynde C, Zirwas M, Maari C, et al. Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: results from the phase 3 randomized, controlled trial (THRIVE‐AA1). J Am Acad Dermatol. 2024;91(5):880–888. [DOI] [PubMed] [Google Scholar]
55. King B, Zhang X, Harcha WG, Szepietowski JC, Shapiro J, Lynde C, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double‐blind, multicentre, phase 2b‐3 trial. Lancet. 2023;401(10387):1518–1529. [DOI] [PubMed] [Google Scholar]
56. Kirby JS, Okun MM, Alavi A, Bechara FG, Zouboulis CC, Brown K, et al. Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double‐blind, dose‐ranging, placebo‐controlled study. J Am Acad Dermatol. 2024;90(3):521–529. [DOI] [PubMed] [Google Scholar]
57. Landis MN, Arya M, Smith S, Draelos Z, Usdan L, Tarabar S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild‐to‐moderate atopic dermatitis: a phase IIb, randomized, double‐blind, vehicle‐controlled, dose‐ranging and parallel‐group study. Br J Dermatol. 2022;187(6):878–887. [DOI] [PMC free article] [PubMed] [Google Scholar]
58. Leng X, Lin W, Liu S, Kanik K, Wang C, Wan W, et al. Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double‐blind, placebo‐controlled study. RMD Open. 2023;9(1):e002559. [DOI] [PMC free article] [PubMed] [Google Scholar]
59. McInnes IB, Anderson JK, Magrey M, Merola JF, Liu Y, Kishimoto M, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384(13):1227–1239. [DOI] [PubMed] [Google Scholar]
60. Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska‐Hanczewska A, Dudek A, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo‐controlled, phase 2 trial. Lancet. 2018;392(10162):2367–2377. [DOI] [PubMed] [Google Scholar]
61. Mease P, Hall S, FitzGerald O, van der Heijde D, Merola JF, Avila‐Zapata F, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377(16):1537–1550. [DOI] [PubMed] [Google Scholar]
62. Mease P, Helliwell P, Silwinska‐Stanczyk P, Miakisz M, Ostor A, Peeva E, et al. Efficacy and safety of the TYK2/JAK1 inhibitor brepocitinib for active psoriatic arthritis: a phase IIb randomized controlled trial. Arthritis Rheum. 2023;75(8):1370–1380. [DOI] [PubMed] [Google Scholar]
63. Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815–822. [DOI] [PMC free article] [PubMed] [Google Scholar]
64. Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT‐PsA 2. Ann Rheum Dis. 2021;80(3):312–320. [DOI] [PMC free article] [PubMed] [Google Scholar]
65. Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE‐052, a Janus kinase inhibitor, in Japanese adult patients with moderate‐to‐severe atopic dermatitis: a phase II, multicentre, randomized, vehicle‐controlled clinical study. Br J Dermatol. 2018;178(2):424–432. [DOI] [PubMed] [Google Scholar]
66. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kabashima K, Oda M, et al. Delgocitinib ointment in pediatric patients with atopic dermatitis: a phase 3, randomized, double‐blind, vehicle‐controlled study and a subsequent open‐label, long‐term study. J Am Acad Dermatol. 2021;85(4):854–862. [DOI] [PubMed] [Google Scholar]
67. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double‐blind, vehicle‐controlled study and an open‐label, long‐term extension study. J Am Acad Dermatol. 2020;82(4):823–831. [DOI] [PubMed] [Google Scholar]
68. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Oda M, Kabashima K, et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis. J Allergy Clin Immunol. 2019;144(6):1575–1583. [DOI] [PubMed] [Google Scholar]
69. Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):1313–1321. [DOI] [PubMed] [Google Scholar]
70. Papp K, Pariser D, Catlin M, Wierz G, Ball G, Akinlade B, et al. A phase 2a randomized, double‐blind, placebo‐controlled, sequential dose‐escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate‐to‐severe psoriasis. Br J Dermatol. 2015;173(3):767–776. [DOI] [PubMed] [Google Scholar]
71. Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double‐blind studies. J Am Acad Dermatol. 2021;85(4):863–872. [DOI] [PubMed] [Google Scholar]
72. Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebo‐controlled dose‐ranging study. Br J Dermatol. 2012;167(3):668–677. [DOI] [PubMed] [Google Scholar]
73. Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo‐controlled, phase III trials. Br J Dermatol. 2015;173(4):949–961. [DOI] [PubMed] [Google Scholar]
74. Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate‐to‐severe psoriasis. Br J Dermatol. 2016;174(6):1266–1276. [DOI] [PubMed] [Google Scholar]
75. Paracha M, Wasim M, Noor SM, Khan AQ, Sagheer F, Ahmad I. Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double‐blind, randomized controlled trial. Arch Dermatol Res. 2024;316(7):458. [DOI] [PubMed] [Google Scholar]
76. Passeron T, Ezzedine K, Hamzavi I, van Geel N, Schlosser BJ, Wu X, et al. Once‐daily upadacitinib versus placebo in adults with extensive non‐segmental vitiligo: a phase 2, multicentre, randomised, double‐blind, placebo‐controlled, dose‐ranging study. EClinicalMedicine. 2024;73:102655. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and safety of Baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(12):1333–1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
78. Reich K, Teixeira HD, de Bruin‐Weller M, Bieber T, Soong W, Kabashima K, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate‐to‐severe atopic dermatitis (AD up): results from a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet. 2021;397(10290):2169–2181. [DOI] [PubMed] [Google Scholar]
79. Reich K, Thyssen JP, Blauvelt A, Eyerich K, Soong W, Rice ZP, et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate‐to‐severe atopic dermatitis: a randomised, double‐blind, multicentre phase 3 trial. Lancet. 2022;400(10348):273–282. [DOI] [PubMed] [Google Scholar]
80. Rosmarin D, Passeron T, Pandya AG, Grimes P, Harris JE, Desai SR, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445–1455. [DOI] [PubMed] [Google Scholar]
81. Schmieder GJ, Draelos ZD, Pariser DM, Banfield C, Cox L, Hodge M, et al. Efficacy and safety of the Janus kinase 1 inhibitor PF‐04965842 in patients with moderate‐to‐severe psoriasis: phase II, randomized, double‐blind, placebo‐controlled study. Br J Dermatol. 2018;179(1):54–62. [DOI] [PubMed] [Google Scholar]
82. Silverberg JI, Bunick CG, Hong HC, Mendes‐Bastos P, Stein Gold L, Costanzo A, et al. Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate‐to‐severe atopic dermatitis: week 16 results of an open‐label randomized efficacy assessor‐blinded head‐to‐head phase IIIb/IV study (level up). Br J Dermatol. 2024;192(1):36–45. [DOI] [PubMed] [Google Scholar]
83. Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and safety of Abrocitinib in patients with moderate‐to‐severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(8):863–873. [DOI] [PMC free article] [PubMed] [Google Scholar]
84. Simpson EL, Forman S, Silverberg JI, Zirwas M, Maverakis E, Han G, et al. Baricitinib in patients with moderate‐to‐severe atopic dermatitis: results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE‐AD5). J Am Acad Dermatol. 2021;85(1):62–70. [DOI] [PubMed] [Google Scholar]
85. Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate‐to‐severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183(2):242–255. [DOI] [PubMed] [Google Scholar]
86. Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate‐to‐severe atopic dermatitis (JADE MONO‐1): a multicentre, double‐blind, randomised, placebo‐controlled, phase 3 trial. Lancet. 2020;396(10246):255–266. [DOI] [PubMed] [Google Scholar]
87. Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52‐week, randomized, double‐blinded, phase 3 program fOr evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88(1):40–51. [DOI] [PubMed] [Google Scholar]
88. Tehlirian C, Singh RSP, Pradhan V, Roberts ES, Tarabar S, Peeva E, et al. Oral tyrosine kinase 2 inhibitor PF‐06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate‐to‐severe plaque psoriasis in a phase 2b, randomized, double‐blind, placebo‐controlled study. J Am Acad Dermatol. 2022;87(2):333–342. [DOI] [PubMed] [Google Scholar]
89. Torrelo A, Rewerska B, Galimberti M, Paller A, Yang CY, Prakash A, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate‐to‐severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double‐blind, placebo‐controlled study (BREEZE‐AD PEDS). Br J Dermatol. 2023;189(1):23–32. [DOI] [PubMed] [Google Scholar]
90. Zhang J, Ding Y, Wang P, Li L, Pan W, Lu Y, et al. Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, in patients from China mainland, Taiwan and South Korea with moderate‐to‐severe plaque psoriasis: a phase III randomized clinical trial. Br J Dermatol. 2024;192(3):402–409. [DOI] [PubMed] [Google Scholar]
91. Zhang J, Tsai TF, Lee MG, Zheng M, Wang G, Jin H, et al. The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: a phase 3, randomized, double‐blind, placebo‐controlled study. J Dermatol Sci. 2017;88(1):36–45. [DOI] [PubMed] [Google Scholar]
92. Zhao Y, Zhang L, Ding Y, Tao X, Ji C, Dong X, et al. Efficacy and safety of SHR0302, a highly selective Janus kinase 1 inhibitor, in patients with moderate to severe atopic dermatitis: a phase II randomized clinical trial. Am J Clin Dermatol. 2021;22(6):877–889. [DOI] [PMC free article] [PubMed] [Google Scholar]
93. Zhou C, Yang X, Yang B, Yan G, Dong X, Ding Y, et al. A randomized, double‐blind, placebo‐controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate‐to‐severe alopecia areata. J Am Acad Dermatol. 2023;89(5):911–919. [DOI] [PubMed] [Google Scholar]
94. Yang G, Seok JK, Kang HC, Cho YY, Lee HS, Lee JY. Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int J Mol Sci. 2020;21(8):2867. [DOI] [PMC free article] [PubMed] [Google Scholar]
95. Droitcourt C, Vittrup I, Kerbrat S, Egeberg A, Thyssen JP. Risk of systemic infections in adults with atopic dermatitis: a nationwide cohort study. J Am Acad Dermatol. 2021;84(2):290–299. [DOI] [PubMed] [Google Scholar]
96. Hoisnard L, Lebrun‐Vignes B, Maury S, Mahevas M, El Karoui K, Roy L, et al. Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Sci Rep. 2022;12(1):7140. [DOI] [PMC free article] [PubMed] [Google Scholar]
97. Arnold KA, Peterson LF, Beck LA, Brewer MG. JAK Signaling is critically important in cytokine‐induced viral susceptibility of keratinocytes. Int J Mol Sci. 2023;24(11):9243. [DOI] [PMC free article] [PubMed] [Google Scholar]
98. Huang IH, Chung WH, Wu PC, Chen CB. JAK‐STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review. Front Immunol. 2022;13:1068260. [DOI] [PMC free article] [PubMed] [Google Scholar]
99. Lee JY, Kim SH, Lee SH, Kim HR, Min HK. Effect of Janus kinase inhibitors on T cell responses to herpes zoster in rheumatoid arthritis patients. Clin Exp Rheumatol. 2023;41(5):1077–1087. [DOI] [PubMed] [Google Scholar]
100. Conrad A, Valour F, Vanhems P. Burden of influenza in the elderly: a narrative review. Curr Opin Infect Dis. 2023;36(4):296–302. [DOI] [PubMed] [Google Scholar]
101. Hagiwara Y, Harada K, Nealon J, Okumura Y, Kimura T, Chaves SS. Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: a descriptive retrospective study in Japan. PLoS One. 2022;17(10):e0272795. [DOI] [PMC free article] [PubMed] [Google Scholar]
102. Pera A, Campos C, López N, Hassouneh F, Alonso C, Tarazona R, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82(1):50–55. [DOI] [PubMed] [Google Scholar]
103. Lewis ED, Wu D, Meydani SN. Age‐associated alterations in immune function and inflammation. Prog Neuro‐Psychopharmacol Biol Psychiatry. 2022;118:110576. [DOI] [PubMed] [Google Scholar]
104. Chen R, Zou J, Chen J, Wang L, Kang R, Tang D. Immune aging and infectious diseases. Chin Med J. 2024;137(24):3010–3049. [DOI] [PMC free article] [PubMed] [Google Scholar]
105. Soiza RL, Scicluna C, Bilal S. Virus infections in older people. Subcell Biochem. 2023;103:149–183. [DOI] [PubMed] [Google Scholar]
106. Rosero CI, Gravenstein S, Saade EA. Influenza and aging: clinical manifestations, complications, and treatment approaches in older adults. Drugs Aging. 2025;42(1):39–55. [DOI] [PubMed] [Google Scholar]
107. Mattei A, Cialfi D, D'Annunzio A, Fabiani L, Fiasca F, Gabutti G. Comorbidities in hospitalized patients with herpes zoster: an Italian retrospective observational study in the years 2011‐2023. BMC Infect Dis. 2025;26(1):185. [DOI] [PMC free article] [PubMed] [Google Scholar]
108. Adas MA, Alveyn E, Cook E, Dey M, Galloway JB, Bechman K. The infection risks of JAK inhibition. Expert Rev Clin Immunol. 2022;18(3):253–261. [DOI] [PMC free article] [PubMed] [Google Scholar]
109. Amstutz A, Schandelmaier S, Ewald H, Speich B, Schwenke JM, Schönenberger CM, et al. Effects of Janus kinase inhibitors in adults admitted to hospital due to COVID‐19: a systematic review and individual participant data meta‐analysis of randomised clinical trials. Lancet Respir Med. 2025;13(6):530–544. [DOI] [PubMed] [Google Scholar]
110. Solimani F, Meier K, Ghoreschi K. Janus kinase signaling as risk factor and therapeutic target for severe SARS‐CoV‐2 infection. Eur J Immunol. 2021;51(5):1071–1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
111. Baughman RP, Meyer KC, Nathanson I, Angel L, Bhorade SM, Chan KM, et al. Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American College of Chest Physicians evidence‐based clinical practice guidelines. Chest. 2012;142(5):e1S–e111S. [DOI] [PMC free article] [PubMed] [Google Scholar]
112. Xu Q, He L, Yin Y. Risk of herpes zoster associated with JAK inhibitors in immune‐mediated inflammatory diseases: a systematic review and network meta‐analysis. Front Pharmacol. 2023;14:1241954. [DOI] [PMC free article] [PubMed] [Google Scholar]
113. Chu DK, Schneider L, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE– and Institute of Medicine–based recommendations. Ann Allergy Asthma Immunol. 2024;132(3):274–312. [DOI] [PubMed] [Google Scholar]
114. Tsai SY‐C, Phipatanakul W, Hawryluk EB, Oyoshi MK, Schneider LC, Ma KS‐K. Comparative safety of oral Janus kinase inhibitors versus dupilumab in patients with atopic dermatitis: a population‐based cohort study. J Allergy Clin Immunol. 2024;154(5):1195–1203.e3. [DOI] [PubMed] [Google Scholar]
115. van der Gang LF, Atash K, Zuithoff NPA, Haeck I, Boesjes CM, Bacoş‐Cosma OI, et al. Infection risk in atopic dermatitis patients treated with biologics and JAK inhibitors: BioDay results. J Eur Acad Dermatol Venereol. 2025;39(12):2056–2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
116. Bunick CG, Irvine AD, Silverberg JI, Guttman‐Yassky E, Shahriari M, Gao X, et al. Safety of upadacitinib in atopic dermatitis in randomized clinical trials across 6 years. J Eur Acad Dermatol Venereol. 2025;40:856–866. [DOI] [PMC free article] [PubMed] [Google Scholar]
117. Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43–e56. [DOI] [PubMed] [Google Scholar]
118. Ciccarese G, Drago F, Herzum A, Atzori L, Dattola A, Galluzzo M, et al. Anti‐herpes zoster vaccination in patients with dermatologic diseases: a position statement from the Italian SIDeMaST group of sexually transmitted, infectious and tropical diseases. Ital J Dermatol Venerol. 2024;159(4):375–379. [DOI] [PubMed] [Google Scholar]
119. Kubo S, Nakayamada S, Sakata K, Kitanaga Y, Ma X, Lee S, et al. Janus kinase inhibitor Baricitinib modulates human innate and adaptive immune system. Front Immunol. 2018;9:1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
120. Balanescu A‐R, Citera G, Pascual‐Ramos V, Bhatt DL, Connell CA, Gold D, et al. Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open‐label, randomised controlled ORAL surveillance trial. Ann Rheum Dis. 2022;81(11):1491–1503. [DOI] [PMC free article] [PubMed] [Google Scholar]
121. Gong X, Chen X, Kuligowski ME, Liu X, Liu X, Cimino E, et al. Pharmacokinetics of ruxolitinib in patients with atopic dermatitis treated with ruxolitinib cream: data from phase II and III studies. Am J Clin Dermatol. 2021;22(4):555–566. [DOI] [PMC free article] [PubMed] [Google Scholar]
122. Sidbury R, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Drucker AM, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1–e20. [DOI] [PubMed] [Google Scholar]
123. Hegyi P, Erőss B, Izbéki F, Párniczky A, Szentesi A. Accelerating the translational medicine cycle: the academia Europaea pilot. Nat Med. 2021;27(8):1317–1319. [DOI] [PubMed] [Google Scholar]
124. Hegyi P, Garami A, Agusti A, Agyemang C, Anadon A, Balla J, et al. Academia Europaea's guidelines for the visualization of clinical outcomes. Nat Med. 2025;31(12):3976–3980. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Figures S1–S72.

Tables S1–S13.

JDV-40-1662-s001.docx^{(3MB, docx)}

Data S2.

JDV-40-1662-s002.docx^{(269.3KB, docx)}

Data Availability Statement

The datasets used in this study can be found in the full‐text articles included in the systematic review and meta‐analysis.

[jdv70508-bib-0001] 1. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10:2342. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0002] 2. Ryguła I, Pikiewicz W, Kaminiów K. Novel Janus kinase inhibitors in the treatment of dermatologic conditions. Molecules. 2023;28(24):8064. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0003] 3. Zhang L, Wang L, Jiang X. The efficacy of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and network meta‐analysis. Dermatol Ther. 2021;34(5):e15098. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0004] 4. Yang F, Lu C, Wang Y, Liu H, Leng X, Zeng X. Efficacy and safety of Janus kinase inhibitors in patients with psoriasis and psoriatic arthritis: a systematic review and meta‐analysis. Clin Rheumatol. 2023;42(6):1593–1605. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0005] 5. Liu M, Gao Y, Yuan Y, Yang K, Shen C, Wang J, et al. Janus kinase inhibitors for alopecia areata: a systematic review and meta‐analysis. JAMA Netw Open. 2023;6(6):e2320351‐e. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0006] 6. Mohammed AA, Lengyel AS, Meznerics FA, Szondy I, Walter A, Szabó B, et al. Efficacy and safety of JAK inhibitors in the Management of vitiligo: a systematic review and meta‐analysis. Dermatol Ther (Heidelb). 2025;15(7):1657–1679. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0007] 7. Garg A, Cohn E, Midgette B, Frasier K, Strunk A. Efficacy and safety of medical interventions for moderate to severe hidradenitis Suppurativa: a living systematic review and network meta‐analysis. JAMA Dermatol. 2025;161(9):931–940. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0008] 8. Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak‐STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–384. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0009] 9. Altınöz Güney C, Koç HA. Investigation of infection risk associated with Janus kinase inhibitors: a pharmacovigilance analysis using the Food and Drug Administration's adverse event reporting system database. Clin Exp Dermatol. 2025;51:226–235. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0010] 10. Yoon S, Kim K, Shin K, Kim HS, Kim B, Kim MB, et al. The safety of systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta‐analysis of randomized controlled trials. J Eur Acad Dermatol Venereol. 2024;38(1):52–61. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0011] 11. Su X, Ou Y, Ruan S, Lv X, Qin K, Mao J, et al. Risk of serious infection with JAK inhibitors in immune‐mediated inflammatory skin diseases: a meta‐analysis of randomized clinical trials. J Dermatol Treat. 2025;36(1):2474507. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0012] 12. Ireland PA, Verheyden M, Jansson N, Sebaratnam D, Sullivan J. Infection risk with JAK inhibitors in dermatoses: a meta‐analysis. Int J Dermatol. 2025;64(1):24–36. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0013] 13. Isufi D, Jensen MB, Loft N, Skov L, Elberling J, Alinaghi F. Risk of infections during treatment with oral Janus kinase inhibitors in randomized placebo‐controlled trials: a systematic review and meta‐analysis. JAAD Int. 2025;18:106–116. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0014] 14. Hegyi P, Varró A. Systems education can train the next generation of scientists and clinicians. Nat Med. 2024;30(12):3399–3400. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0015] 15. Hegyi P, Petersen OH, Holgate S, Erőss B, Garami A, Szakács Z, et al. Academia Europaea position paper on translational medicine: the cycle model for translating scientific results into community benefits. J Clin Med. 2020;9(5):1532. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0016] 16. Cochrane . Cochrane handbook for systematic reviews of interventions. Cochrane; 2024. Available from: https://www.cochrane.org/handbook. [Google Scholar]

[jdv70508-bib-0017] 17. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0018] 18. Bramer WM, Giustini D, de Jonge GB, Holland L, Bekhuis T. De‐duplication of database search results for systematic reviews in EndNote. J Med Libr Assoc. 2016;104(3):240–243. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0019] 19. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan‐a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0020] 20. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0021] 21. GDT G . GRADEpro guideline development tool. McMaster University and Evidence Prime; 2023. [Google Scholar]

[jdv70508-bib-0022] 22. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. 2002;21(11):1539–1558. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0023] 23. Team RC . R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2024. [Google Scholar]

[jdv70508-bib-0024] 24. Alavi A, Hamzavi I, Brown K, Santos LL, Zhu Z, Liu H, et al. Janus kinase 1 inhibitor INCB054707 for patients with moderate‐to‐severe hidradenitis suppurativa: results from two phase II studies. Br J Dermatol. 2022;186(5):803–813. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0025] 25. Anderson S, Cavaletti G, Hood LJ, Polydefkis M, Herrmann DN, Rance G, et al. A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata. Pharmacol Res Perspect. 2024;12(4):e1204. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0026] 26. Armstrong AW, Gooderham M, Lynde C, Maari C, Forman S, Green L, et al. Tyrosine kinase 2 inhibition with zasocitinib (TAK‐279) in psoriasis: a randomized clinical trial. JAMA Dermatol. 2024;160(10):1066–1074. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0027] 27. Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52‐week, randomized, double‐blinded, placebo‐controlled phase 3 POETYK PSO‐1 trial. J Am Acad Dermatol. 2023;88(1):29–39. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0028] 28. Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib versus etanercept or placebo in moderate‐to‐severe chronic plaque psoriasis: a phase 3 randomised non‐inferiority trial. Lancet. 2015;386(9993):552–561. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0029] 29. Bieber T, Reich K, Paul C, Tsunemi Y, Augustin M, Lacour JP, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate‐to‐severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo‐controlled, phase III clinical trial (BREEZE‐AD4). Br J Dermatol. 2022;187(3):338–352. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0030] 30. Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101–1112. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0031] 31. Bissonnette R, Iversen L, Sofen H, Griffiths CE, Foley P, Romiti R, et al. Tofacitinib withdrawal and retreatment in moderate‐to‐severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172(5):1395–1406. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0032] 32. Bissonnette R, Luchi M, Fidelus‐Gort R, Jackson S, Zhang H, Flores R, et al. A randomized, double‐blind, placebo‐controlled, dose‐escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis. J Dermatolog Treat. 2016;27(4):332–338. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0033] 33. Bissonnette R, Maari C, Forman S, Bhatia N, Lee M, Fowler J, et al. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate‐to‐severe atopic dermatitis: results from a randomized double‐blind placebo‐controlled study. Br J Dermatol. 2019;181(4):733–742. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0034] 34. Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–911. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0035] 35. Blauvelt A, Silverberg JI, Lynde CW, Bieber T, Eisman S, Zdybski J, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate‐to‐severe atopic dermatitis: results from the JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN phase 3 trial. J Am Acad Dermatol. 2022;86(1):104–112. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0036] 36. Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin‐Weller M, Barbarot S, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate‐to‐severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157(9):1047–1055. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0037] 37. Changelian P, Xu C, Mnich S, Hope H, Kostecki K, Hirsch J, et al. ATI‐1777, a topical Jak1/3 inhibitor, may benefit atopic dermatitis without systemic drug exposure: results from preclinical development and phase 2a randomized control study ATI‐1777‐AD‐201. JID Innov. 2024;4(2):100251. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0038] 38. David E, Shokrian N, Del Duca E, Meariman M, Dubin C, Hawkins K, et al. A phase 2a trial of brepocitinib for cicatricial alopecia. J Am Acad Dermatol. 2025;92(3):427–434. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0039] 39. Eichenfield LF, Flohr C, Sidbury R, Siegfried E, Szalai Z, Galus R, et al. Efficacy and safety of abrocitinib in combination with topical therapy in adolescents with moderate‐to‐severe atopic dermatitis: the JADE TEEN randomized clinical trial. JAMA Dermatol. 2021;157(10):1165–1173. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0040] 40. Ezzedine K, Peeva E, Yamaguchi Y, Cox LA, Banerjee A, Han G, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88(2):395–403. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0041] 41. Forman SB, Pariser DM, Poulin Y, Vincent MS, Gilbert SA, Kieras EM, et al. TYK2/JAK1 inhibitor PF‐06700841 in patients with plaque psoriasis: phase IIa, randomized, double‐blind, placebo‐controlled trial. J Invest Dermatol. 2020;140(12):2359–2370.e5. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0042] 42. Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377(16):1525–1536. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0043] 43. Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of Oral Janus kinase 1 inhibitor Abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. JAMA Dermatol. 2019;155(12):1371–1379. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0044] 44. Guttman‐Yassky E, Facheris P, Gomez‐Arias PJ, Del Duca E, Da Rosa JC, Weidinger S, et al. Effect of abrocitinib on skin biomarkers in patients with moderate‐to‐severe atopic dermatitis. Allergy. 2024;79(5):1258–1270. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0045] 45. Guttman‐Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate‐to‐severe atopic dermatitis: a phase 2 parallel, double‐blinded, randomized placebo‐controlled multiple‐dose study. J Am Acad Dermatol. 2019;80(4):913–921.e9. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0046] 46. Guttman‐Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, et al. Once‐daily upadacitinib versus placebo in adolescents and adults with moderate‐to‐severe atopic dermatitis (measure up 1 and measure up 2): results from two replicate double‐blind, randomised controlled phase 3 trials. Lancet. 2021;397(10290):2151–2168. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0047] 47. Guttman‐Yassky E, Thaçi D, Pangan AL, Hong HC, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16‐week results from a randomized, placebo‐controlled trial. J Allergy Clin Immunol. 2020;145(3):877–884. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0048] 48. Katoh N, Ohya Y, Murota H, Ikeda M, Hu X, Ikeda K, et al. Safety and efficacy of upadacitinib for atopic dermatitis in Japan: 2‐year interim results from the phase 3 rising up study. Dermatol Ther (Heidelb). 2023;13(1):221–234. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0049] 49. Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572–582. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0050] 50. Kimball AB, Peeva E, Forman S, Moiin A, Khattri S, Porter ML, et al. Brepocitinib, zimlovisertib, and ropsacitinib in hidradenitis suppurativa. NEJM Evid. 2024;3(3):EVIDoa2300155. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0051] 51. King B, Guttman‐Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, et al. A phase 2a randomized, placebo‐controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24‐week results. J Am Acad Dermatol. 2021;85(2):379–387. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0052] 52. King B, Mesinkovska N, Mirmirani P, Bruce S, Kempers S, Guttman‐Yassky E, et al. Phase 2 randomized, dose‐ranging trial of CTP‐543, a selective Janus kinase inhibitor, in moderate‐to‐severe alopecia areata. J Am Acad Dermatol. 2022;87(2):306–313. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0053] 53. King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687–1699. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0054] 54. King B, Senna MM, Mesinkovska NA, Lynde C, Zirwas M, Maari C, et al. Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: results from the phase 3 randomized, controlled trial (THRIVE‐AA1). J Am Acad Dermatol. 2024;91(5):880–888. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0055] 55. King B, Zhang X, Harcha WG, Szepietowski JC, Shapiro J, Lynde C, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double‐blind, multicentre, phase 2b‐3 trial. Lancet. 2023;401(10387):1518–1529. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0056] 56. Kirby JS, Okun MM, Alavi A, Bechara FG, Zouboulis CC, Brown K, et al. Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double‐blind, dose‐ranging, placebo‐controlled study. J Am Acad Dermatol. 2024;90(3):521–529. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0057] 57. Landis MN, Arya M, Smith S, Draelos Z, Usdan L, Tarabar S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild‐to‐moderate atopic dermatitis: a phase IIb, randomized, double‐blind, vehicle‐controlled, dose‐ranging and parallel‐group study. Br J Dermatol. 2022;187(6):878–887. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0058] 58. Leng X, Lin W, Liu S, Kanik K, Wang C, Wan W, et al. Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double‐blind, placebo‐controlled study. RMD Open. 2023;9(1):e002559. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0059] 59. McInnes IB, Anderson JK, Magrey M, Merola JF, Liu Y, Kishimoto M, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384(13):1227–1239. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0060] 60. Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska‐Hanczewska A, Dudek A, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo‐controlled, phase 2 trial. Lancet. 2018;392(10162):2367–2377. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0061] 61. Mease P, Hall S, FitzGerald O, van der Heijde D, Merola JF, Avila‐Zapata F, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377(16):1537–1550. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0062] 62. Mease P, Helliwell P, Silwinska‐Stanczyk P, Miakisz M, Ostor A, Peeva E, et al. Efficacy and safety of the TYK2/JAK1 inhibitor brepocitinib for active psoriatic arthritis: a phase IIb randomized controlled trial. Arthritis Rheum. 2023;75(8):1370–1380. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0063] 63. Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815–822. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0064] 64. Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT‐PsA 2. Ann Rheum Dis. 2021;80(3):312–320. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0065] 65. Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE‐052, a Janus kinase inhibitor, in Japanese adult patients with moderate‐to‐severe atopic dermatitis: a phase II, multicentre, randomized, vehicle‐controlled clinical study. Br J Dermatol. 2018;178(2):424–432. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0066] 66. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kabashima K, Oda M, et al. Delgocitinib ointment in pediatric patients with atopic dermatitis: a phase 3, randomized, double‐blind, vehicle‐controlled study and a subsequent open‐label, long‐term study. J Am Acad Dermatol. 2021;85(4):854–862. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0067] 67. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double‐blind, vehicle‐controlled study and an open‐label, long‐term extension study. J Am Acad Dermatol. 2020;82(4):823–831. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0068] 68. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Oda M, Kabashima K, et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis. J Allergy Clin Immunol. 2019;144(6):1575–1583. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0069] 69. Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):1313–1321. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0070] 70. Papp K, Pariser D, Catlin M, Wierz G, Ball G, Akinlade B, et al. A phase 2a randomized, double‐blind, placebo‐controlled, sequential dose‐escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate‐to‐severe psoriasis. Br J Dermatol. 2015;173(3):767–776. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0071] 71. Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double‐blind studies. J Am Acad Dermatol. 2021;85(4):863–872. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0072] 72. Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebo‐controlled dose‐ranging study. Br J Dermatol. 2012;167(3):668–677. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0073] 73. Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo‐controlled, phase III trials. Br J Dermatol. 2015;173(4):949–961. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0074] 74. Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate‐to‐severe psoriasis. Br J Dermatol. 2016;174(6):1266–1276. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0075] 75. Paracha M, Wasim M, Noor SM, Khan AQ, Sagheer F, Ahmad I. Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double‐blind, randomized controlled trial. Arch Dermatol Res. 2024;316(7):458. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0076] 76. Passeron T, Ezzedine K, Hamzavi I, van Geel N, Schlosser BJ, Wu X, et al. Once‐daily upadacitinib versus placebo in adults with extensive non‐segmental vitiligo: a phase 2, multicentre, randomised, double‐blind, placebo‐controlled, dose‐ranging study. EClinicalMedicine. 2024;73:102655. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0077] 77. Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and safety of Baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(12):1333–1343. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0078] 78. Reich K, Teixeira HD, de Bruin‐Weller M, Bieber T, Soong W, Kabashima K, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate‐to‐severe atopic dermatitis (AD up): results from a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet. 2021;397(10290):2169–2181. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0079] 79. Reich K, Thyssen JP, Blauvelt A, Eyerich K, Soong W, Rice ZP, et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate‐to‐severe atopic dermatitis: a randomised, double‐blind, multicentre phase 3 trial. Lancet. 2022;400(10348):273–282. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0080] 80. Rosmarin D, Passeron T, Pandya AG, Grimes P, Harris JE, Desai SR, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445–1455. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0081] 81. Schmieder GJ, Draelos ZD, Pariser DM, Banfield C, Cox L, Hodge M, et al. Efficacy and safety of the Janus kinase 1 inhibitor PF‐04965842 in patients with moderate‐to‐severe psoriasis: phase II, randomized, double‐blind, placebo‐controlled study. Br J Dermatol. 2018;179(1):54–62. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0082] 82. Silverberg JI, Bunick CG, Hong HC, Mendes‐Bastos P, Stein Gold L, Costanzo A, et al. Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate‐to‐severe atopic dermatitis: week 16 results of an open‐label randomized efficacy assessor‐blinded head‐to‐head phase IIIb/IV study (level up). Br J Dermatol. 2024;192(1):36–45. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0083] 83. Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and safety of Abrocitinib in patients with moderate‐to‐severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(8):863–873. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0084] 84. Simpson EL, Forman S, Silverberg JI, Zirwas M, Maverakis E, Han G, et al. Baricitinib in patients with moderate‐to‐severe atopic dermatitis: results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE‐AD5). J Am Acad Dermatol. 2021;85(1):62–70. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0085] 85. Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate‐to‐severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183(2):242–255. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0086] 86. Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate‐to‐severe atopic dermatitis (JADE MONO‐1): a multicentre, double‐blind, randomised, placebo‐controlled, phase 3 trial. Lancet. 2020;396(10246):255–266. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0087] 87. Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52‐week, randomized, double‐blinded, phase 3 program fOr evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88(1):40–51. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0088] 88. Tehlirian C, Singh RSP, Pradhan V, Roberts ES, Tarabar S, Peeva E, et al. Oral tyrosine kinase 2 inhibitor PF‐06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate‐to‐severe plaque psoriasis in a phase 2b, randomized, double‐blind, placebo‐controlled study. J Am Acad Dermatol. 2022;87(2):333–342. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0089] 89. Torrelo A, Rewerska B, Galimberti M, Paller A, Yang CY, Prakash A, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate‐to‐severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double‐blind, placebo‐controlled study (BREEZE‐AD PEDS). Br J Dermatol. 2023;189(1):23–32. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0090] 90. Zhang J, Ding Y, Wang P, Li L, Pan W, Lu Y, et al. Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, in patients from China mainland, Taiwan and South Korea with moderate‐to‐severe plaque psoriasis: a phase III randomized clinical trial. Br J Dermatol. 2024;192(3):402–409. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0091] 91. Zhang J, Tsai TF, Lee MG, Zheng M, Wang G, Jin H, et al. The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: a phase 3, randomized, double‐blind, placebo‐controlled study. J Dermatol Sci. 2017;88(1):36–45. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0092] 92. Zhao Y, Zhang L, Ding Y, Tao X, Ji C, Dong X, et al. Efficacy and safety of SHR0302, a highly selective Janus kinase 1 inhibitor, in patients with moderate to severe atopic dermatitis: a phase II randomized clinical trial. Am J Clin Dermatol. 2021;22(6):877–889. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0093] 93. Zhou C, Yang X, Yang B, Yan G, Dong X, Ding Y, et al. A randomized, double‐blind, placebo‐controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate‐to‐severe alopecia areata. J Am Acad Dermatol. 2023;89(5):911–919. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0094] 94. Yang G, Seok JK, Kang HC, Cho YY, Lee HS, Lee JY. Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int J Mol Sci. 2020;21(8):2867. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0095] 95. Droitcourt C, Vittrup I, Kerbrat S, Egeberg A, Thyssen JP. Risk of systemic infections in adults with atopic dermatitis: a nationwide cohort study. J Am Acad Dermatol. 2021;84(2):290–299. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0096] 96. Hoisnard L, Lebrun‐Vignes B, Maury S, Mahevas M, El Karoui K, Roy L, et al. Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Sci Rep. 2022;12(1):7140. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0097] 97. Arnold KA, Peterson LF, Beck LA, Brewer MG. JAK Signaling is critically important in cytokine‐induced viral susceptibility of keratinocytes. Int J Mol Sci. 2023;24(11):9243. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0098] 98. Huang IH, Chung WH, Wu PC, Chen CB. JAK‐STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review. Front Immunol. 2022;13:1068260. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0099] 99. Lee JY, Kim SH, Lee SH, Kim HR, Min HK. Effect of Janus kinase inhibitors on T cell responses to herpes zoster in rheumatoid arthritis patients. Clin Exp Rheumatol. 2023;41(5):1077–1087. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0100] 100. Conrad A, Valour F, Vanhems P. Burden of influenza in the elderly: a narrative review. Curr Opin Infect Dis. 2023;36(4):296–302. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0101] 101. Hagiwara Y, Harada K, Nealon J, Okumura Y, Kimura T, Chaves SS. Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: a descriptive retrospective study in Japan. PLoS One. 2022;17(10):e0272795. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0102] 102. Pera A, Campos C, López N, Hassouneh F, Alonso C, Tarazona R, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82(1):50–55. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0103] 103. Lewis ED, Wu D, Meydani SN. Age‐associated alterations in immune function and inflammation. Prog Neuro‐Psychopharmacol Biol Psychiatry. 2022;118:110576. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0104] 104. Chen R, Zou J, Chen J, Wang L, Kang R, Tang D. Immune aging and infectious diseases. Chin Med J. 2024;137(24):3010–3049. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0105] 105. Soiza RL, Scicluna C, Bilal S. Virus infections in older people. Subcell Biochem. 2023;103:149–183. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0106] 106. Rosero CI, Gravenstein S, Saade EA. Influenza and aging: clinical manifestations, complications, and treatment approaches in older adults. Drugs Aging. 2025;42(1):39–55. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0107] 107. Mattei A, Cialfi D, D'Annunzio A, Fabiani L, Fiasca F, Gabutti G. Comorbidities in hospitalized patients with herpes zoster: an Italian retrospective observational study in the years 2011‐2023. BMC Infect Dis. 2025;26(1):185. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0108] 108. Adas MA, Alveyn E, Cook E, Dey M, Galloway JB, Bechman K. The infection risks of JAK inhibition. Expert Rev Clin Immunol. 2022;18(3):253–261. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0109] 109. Amstutz A, Schandelmaier S, Ewald H, Speich B, Schwenke JM, Schönenberger CM, et al. Effects of Janus kinase inhibitors in adults admitted to hospital due to COVID‐19: a systematic review and individual participant data meta‐analysis of randomised clinical trials. Lancet Respir Med. 2025;13(6):530–544. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0110] 110. Solimani F, Meier K, Ghoreschi K. Janus kinase signaling as risk factor and therapeutic target for severe SARS‐CoV‐2 infection. Eur J Immunol. 2021;51(5):1071–1075. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0111] 111. Baughman RP, Meyer KC, Nathanson I, Angel L, Bhorade SM, Chan KM, et al. Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American College of Chest Physicians evidence‐based clinical practice guidelines. Chest. 2012;142(5):e1S–e111S. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0112] 112. Xu Q, He L, Yin Y. Risk of herpes zoster associated with JAK inhibitors in immune‐mediated inflammatory diseases: a systematic review and network meta‐analysis. Front Pharmacol. 2023;14:1241954. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0113] 113. Chu DK, Schneider L, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE– and Institute of Medicine–based recommendations. Ann Allergy Asthma Immunol. 2024;132(3):274–312. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0114] 114. Tsai SY‐C, Phipatanakul W, Hawryluk EB, Oyoshi MK, Schneider LC, Ma KS‐K. Comparative safety of oral Janus kinase inhibitors versus dupilumab in patients with atopic dermatitis: a population‐based cohort study. J Allergy Clin Immunol. 2024;154(5):1195–1203.e3. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0115] 115. van der Gang LF, Atash K, Zuithoff NPA, Haeck I, Boesjes CM, Bacoş‐Cosma OI, et al. Infection risk in atopic dermatitis patients treated with biologics and JAK inhibitors: BioDay results. J Eur Acad Dermatol Venereol. 2025;39(12):2056–2068. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0116] 116. Bunick CG, Irvine AD, Silverberg JI, Guttman‐Yassky E, Shahriari M, Gao X, et al. Safety of upadacitinib in atopic dermatitis in randomized clinical trials across 6 years. J Eur Acad Dermatol Venereol. 2025;40:856–866. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0117] 117. Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43–e56. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0118] 118. Ciccarese G, Drago F, Herzum A, Atzori L, Dattola A, Galluzzo M, et al. Anti‐herpes zoster vaccination in patients with dermatologic diseases: a position statement from the Italian SIDeMaST group of sexually transmitted, infectious and tropical diseases. Ital J Dermatol Venerol. 2024;159(4):375–379. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0119] 119. Kubo S, Nakayamada S, Sakata K, Kitanaga Y, Ma X, Lee S, et al. Janus kinase inhibitor Baricitinib modulates human innate and adaptive immune system. Front Immunol. 2018;9:1510. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0120] 120. Balanescu A‐R, Citera G, Pascual‐Ramos V, Bhatt DL, Connell CA, Gold D, et al. Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open‐label, randomised controlled ORAL surveillance trial. Ann Rheum Dis. 2022;81(11):1491–1503. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0121] 121. Gong X, Chen X, Kuligowski ME, Liu X, Liu X, Cimino E, et al. Pharmacokinetics of ruxolitinib in patients with atopic dermatitis treated with ruxolitinib cream: data from phase II and III studies. Am J Clin Dermatol. 2021;22(4):555–566. [DOI] [PMC free article] [PubMed] [Google Scholar]

[jdv70508-bib-0122] 122. Sidbury R, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Drucker AM, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1–e20. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0123] 123. Hegyi P, Erőss B, Izbéki F, Párniczky A, Szentesi A. Accelerating the translational medicine cycle: the academia Europaea pilot. Nat Med. 2021;27(8):1317–1319. [DOI] [PubMed] [Google Scholar]

[jdv70508-bib-0124] 124. Hegyi P, Garami A, Agusti A, Agyemang C, Anadon A, Balla J, et al. Academia Europaea's guidelines for the visualization of clinical outcomes. Nat Med. 2025;31(12):3976–3980. [DOI] [PubMed] [Google Scholar]

PERMALINK

Large‐scale meta‐analysis of infection risk with JAK–STAT inhibitors in 29,000 patients

Máté Krebs

Lili Gulyás

Karen Krisztina Fazekas

Benedek Nagy

Mária Veronika Kolonics

Fanni Adél Meznerics

Norbert Kiss

András Bánvölgyi

Péter Hegyi

Péter Holló

Lajos Vince Kemény

Abstract

Introduction

Methods

Results

Conclusions

Why was the study undertaken?

What does this study add?

What are the implications of this study for disease understanding and/or clinical care?

INTRODUCTION

METHODS

Eligibility criteria

Search strategy and selection process

Data collection and synthesis

Statistical analysis

RESULTS

Search and selection

FIGURE 1.

Basic characteristics of included studies

Quantitative analysis

TABLE 1.

FIGURE 2.

FIGURE 3.

Qualitative analysis

Risk of bias assessment

Publication bias

Certainty of evidence

DISCUSSION

Strengths

Limitations

Implication for practice and research

CONCLUSIONS

AUTHOR CONTRIBUTIONS

FUNDING INFORMATION

CONFLICT OF INTEREST STATEMENT

ETHICAL APPROVAL

ETHICS STATEMENT

Supporting information

Contributor Information

DATA AVAILABILITY STATEMENT

REFERENCES

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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