Abstract
In patients with moderate to severe atopic dermatitis (AD) showing an inadequate response to dupilumab 300mg/2weeks, few real-life studies reported the response to alternative regimen maintaining dupilumab.
To assess and analyze the response to an increased dose of dupilumab or its combination with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA), all adult AD patients from 7 French University Hospitals were retrospectively included if they achieved an inadequate response to dupilumab 300mg/2weeks and were subsequently treated with an increased dose of dupilumab (300mg every 7 or 10 days), or a combination of dupilumab 300mg/2weeks with CsA, MTX or ITRA. The response after 3 months, along with epidemiological, clinical, and therapeutic baseline characteristics, were collected.
Overall, 68.75% of the 48 included patients achieved an improved response, including 45.8% of complete response (CR). No strategy proved significantly better. Patients showing an initial no response never achieved a further CR versus 52.4% of patients with an initial partial response (p = 0.025). Digestive intolerance and tachycardia led to MTX and ITRA discontinuation in 3 patients.
Increasing the dose of dupilumab or combining it with CsA, MTX, or ITRA could be alternative and safe options, to be evaluated in further medico-economic studies.
Keywords: Dermatitis, Atopic, Dupilumab, Cyclosporine, Methotrexate, Itraconazole
Introduction
Dupilumab has demonstrated its good safety profile and efficacy over time in patients with moderate to severe atopic dermatitis (AD) in pivotal1 and real-life studies.2 Few real-life studies describe the management of patients with an inadequate response to on-label use of dupilumab, despite published algorithms propose to increase the dose, or to combine with immunosuppressive drugs,3,4 or to switch for oral Janus Kinase inhibitors (JAKi).5,6
We conducted a multicenter retrospective study to i) assess the response to increased dose of dupilumab or combination with other systemic agents and ii) analyze epidemiological and clinical factors associated with this response.
Population and methods
This study was conducted in 7 French University Hospitals. We included all adult AD patients between March 2017 and March 2021 with an inadequate response to dupilumab 300 mg every 2 weeks and were subsequently treated with any of the following strategies: increasing the dose of dupilumab (300mg every 7 or 10 days); combination of dupilumab 300 mg every 2 weeks with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA). Response was assessed after 3–6 months of any treatment option; thus data were collected between November 2020 and June 2021 from medical files. A complete response (CR) was defined as achieving an Investigator's Global Assessment (IGA) score of 0/1 or improvement 2 points, and/or a Dermatology Life Quality Index (DLQI)<10, and/or reaching a 75% improvement of the eczema area scoring index (EASI75). An inadequate response was defined as a partial response (PR) (IGA = 2 and/or 10≤DLQI<20 and/or a 25–50% decrease in EASI and/or de novo or worsening head-and-neck dermatitis (HAND)) or no response (NR) (IGA>2 and/or DLQI≥20 and/or a 0–25% decrease in EASI).
Additionally, we collected the following data: age, gender, weight, previous treatments, initial response to dupilumab, and practicians’ alleged reason for choosing any of the above-mentioned therapeutic options.
Statistics analysis
The categorical variables are presented with their associated numbers and compared using the Fisher's test. The quantitative variables are presented with their means and extreme values of the series (lower, higher) and compared via a Student's t-test (or Wilcoxon Mann Whitney test if the conditions of validity were not met) for comparisons with 2 groups and ANOVA (or Kruskal Wallis if the conditions of validity were not met) for comparisons with more than 2 groups. The results of the statistical tests of comparison are presented as p-values. A difference was considered significant if the p-value was less than 0.05.
Results
Forty-eight patients were included (30 men): 42 patients had shown a PR (87.5%) and 6 had shown NR (12.5%) after 3 months of dupilumab 300mg/2 weeks. Their baseline characteristics are presented in Table 1. To be noted, 21.4% of the PR patients had a de novo or worsening HAND. As shown in Table 2, 21 patients received an increased dose of dupilumab (300mg/7 or 10 days), and 27 received a combination of dupilumab 300mg/2 weeks with 1 of the following drugs: CsA (3–5mg/kg every day or twice a week) in 5 patients previously prescribed with CsA; MTX (mean dosage 13.1mg/week, range 10–20) in 14 patients including 5 previously prescribed with MTX; ITRA (28.5–200mg/day) in 8 ITRA-naïve patients. Patients with a de novo or worsening HAND were more likely to be prescribed with additional ITRA. Patients with a higher baseline EASI at dupilumab initiation were more likely to be prescribed with additional CsA, whereas patients who were prescribed with additional MTX had a lower EASI. Patients with a higher weight at dupilumab initiation were less likely to be prescribed with additional MTX than an increased dose of dupilumab (Table S1).
Table 1.
Baseline characteristics of the 48 patients with an initial inadequate response after 3 months of dupilumab 300mg/2weeks.
| Age, mean (range), years | 36 (19–64) |
| Sex ratio M/F | 1.67 |
| Weight, mean (range), kg | 70.8 (45–118) |
| Baseline SCORAD at dupilumab initiation, mean (range) n = 39 | 53 (18–94) |
| Baseline IGA at dupilumab initiation, mean (range) n = 38 | 3.3 (2–4) |
| Baseline EASI at dupilumab initiation, mean (range) n = 23 | 19.4 (2.1–49) |
| Baseline DLQI at dupilumab initiation, mean (range) n = 35 | 15.8 (1–30) |
| Previous treatment with cyclosporin A, number of patients (%) | 37 (77.1) |
| Previous treatment with methotrexate, number of patients (%) | 22 (45.8) |
| Previous treatment with phototherapy, number of patients (%) | 28 (58.3) |
M male, F female, SCORAD SCORing Atopic Dermatitis, IGA Investigator's Global Assessment, EASI Eczema Area and Severity Index, DLQI Dermatology Life Quality Index, n number of patients with available data.
Table 2.
Characteristics of the patients and response to treatment options.
| Number of patient | Gender | Age, years | Weight, kg | Treatment prior to dupilumab |
Scores at dupilumab initiation |
Initial response to dupilumab (M3) | De novo or worsening of a HAND in patients with partial response to dupilumab (M3) | Treatment options | Response to the treatment options (M3) | Subsequent treatment with JAKi, mg/day | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MTX | Photo-therapy | CsA | SCORAD | DLQI | EASI | IGA | |||||||||
| 1 | m | 23 | 63 | 1 | na | na | na | 2 | PR | Combination of dupilumab with CsA | CR | ||||
| 2 | m | 31 | 65 | 1 | 33.1 | 9 | na | na | PR | yes | Combination of dupilumab with MTX | CR | |||
| 3 | m | 27 | 75 | 1 | 50.3 | 25 | na | 4 | PR | Combination of dupilumab with MTX | NR | upadacitinib 30 | |||
| 4 | m | 48 | 80 | 1 | 1 | 47 | 19 | na | 4 | NR | Combination of dupilumab with CsA | PR | |||
| 5 | m | 60 | 70 | 1 | 1 | 60 | 13 | na | na | NR | Combination of dupilumab with MTX | PR | upadacitinib 30 | ||
| 6 | m | 26 | 80 | 1 | 51.6 | 7 | na | na | PR | Increased dose of dupilumab | CR | ||||
| 7 | f | 48 | 95 | 1 | 56 | 23 | na | na | PR | yes | Combination of dupilumab with ITRA | NR | |||
| 8 | f | 33 | 64 | 1 | 1 | na | na | na | 3 | PR | Increased dose of dupilumab | CR | |||
| 9 | m | 57 | 59 | 1 | 1 | 67 | na | na | na | PR | Increased dose of dupilumab | CR | |||
| 10 | m | 38 | 95 | 1 | 18 | na | na | na | PR | Combination of dupilumab with CsA | CR | ||||
| 11 | m | 28 | 84 | 29.2 | na | na | na | PR | Combination of dupilumab with ITRA | NR | |||||
| 12 | m | 39 | 70 | 1 | 51 | 14 | 16 | 3 | PR | yes | Combination of dupilumab with ITRA | NR | |||
| 13 | f | 36 | 51 | 1 | 1 | 1 | 45 | 24 | 2.1 | 2 | PR | Combination of dupilumab with MTX | NR | ||
| 14 | m | 21 | 60 | 1 | 1 | 1 | 46 | 27 | na | 3 | PR | Increased dose of dupilumab | PR | ||
| 15 | f | 32 | 56 | 1 | na | 3 | 17.6 | 3 | PR | Increased dose of dupilumab | CR | ||||
| 16 | m | 51 | 83 | 1 | 1 | 26 | 3 | 14.7 | 2 | PR | yes | Combination of dupilumab with ITRA | CR | ||
| 17 | m | 30 | 63 | 1 | 1 | 1 | 94 | 30 | 49 | 4 | PR | Combination of dupilumab with CsA | CR | ||
| 18 | f | 39 | 93 | 1 | 1 | 55 | 25 | 19 | 4 | PR | Increased dose of dupilumab | CR | |||
| 19 | m | 34 | 85 | 1 | 1 | 50 | 23 | 11 | 3 | NR | Increased dose of dupilumab | PR | |||
| 20 | f | 27 | 53 | 1 | 63 | 22.8 | 3 | RP | Increased dose of dupilumab | NR | upadacitinib 30 | ||||
| 21 | f | 61 | 88 | 1 | 1 | 1 | 70 | 25 | 20 | 4 | RP | yes | Combination of dupilumab with ITRA | CR | |
| 22 | f | 26 | 53 | 1 | 1 | 47 | 20 | 17 | 4 | RP | Combination of dupilumab with CsA | PR | |||
| 23 | f | 44 | 55 | 1 | 1 | 38 | 25 | 12 | 3 | RP | yes | Combination of dupilumab with ITRA | CR | ||
| 24 | m | 36 | 95 | 1 | 1 | 1 | 55 | 26 | 18 | 4 | RP | Increased dose of dupilumab | NR | baracitinib 4 | |
| 25 | m | 26 | 63 | 1 | 1 | 30.5 | 5 | 5 | 2 | RP | yes | Combination of dupilumab with ITRA | PR | ||
| 26 | m | 40 | 70 | 1 | 1 | 26 | 6 | 4.5 | 2 | RP | Combination of dupilumab with MTX | CR | |||
| 27 | f | 24 | 63 | 1 | 72.5 | 21 | 25.2 | 4 | RP | Combination of dupilumab with MTX | CR | ||||
| 28 | f | 49 | 69 | 1 | 60 | 12 | 10.4 | 4 | RP | Combination of dupilumab with MTX | PR | ||||
| 29 | m | 26 | 62 | 1 | 1 | 1 | 71.5 | 14 | 16.4 | 4 | RP | yes | Combination of dupilumab with MTX | PR | |
| 30 | m | 34 | 88 | 1 | 1 | 1 | na | na | na | 4 | NR | Combination of dupilumab with MTX | NR | ||
| 31 | m | 32 | 79 | 1 | 1 | 68.3 | 4 | 36.3 | 3 | PR | Increased dose of dupilumab | CR | |||
| 32 | f | 22 | 65 | 1 | 42 | 8 | 29.6 | 3 | PR | Increased dose of dupilumab | NR | upadacitinib 30 | |||
| 33 | m | 22 | 78 | 1 | 1 | 38 | 3 | na | na | NR | Increased dose of dupilumab | NR | |||
| 34 | f | 35 | 90 | 1 | 1 | 48 | na | na | na | NR | Increased dose of dupilumab | NR | |||
| 35 | m | 42 | 69 | 1 | 1 | 1 | na | na | na | 3 | PR | Increased dose of dupilumab | CR | ||
| 36 | f | 45 | 78 | 1 | 1 | 1 | 82 | 16 | na | 3 | PR | Increased dose of dupilumab | NR | upadacitinib 30 | |
| 37 | m | 56 | 118 | 41 | 18 | na | 3 | PR | Increased dose of dupilumab | CR | |||||
| 38 | m | 19 | 46 | 1 | 64 | 8 | na | 3 | PR | Combination of dupilumab with MTX | CR | ||||
| 39 | m | 44 | 48 | 1 | 1 | 68 | 21 | na | 3 | PR | Combination of dupilumab with MTX | CR | |||
| 40 | m | 64 | 75 | 1 | 1 | 63 | 7 | na | 3 | PR | Combination of dupilumab with MTX | CR | |||
| 41 | f | 37 | 45 | 1 | 1 | 1 | 30 | 7 | na | 2 | PR | Combination of dupilumab with MTX | CR | upadacitinib 30 | |
| 42 | m | 21 | 62 | 1 | na | na | na | na | PR | yes | Combination of dupilumab with ITRA | PR | |||
| 43 | m | 51 | 67 | 1 | 1 | 76 | 29 | 34.4 | 4 | PR | Increased dose of dupilumab | PR | upadacitinib 30 | ||
| 44 | f | 29 | 66 | 1 | 1 | 1 | 69 | 5 | 18.5 | 4 | PR | Increased dose of dupilumab | NR | upadacitinib 30 | |
| 45 | f | 52 | 68 | 1 | 1 | 1 | 66 | na | 24 | 4 | PR | Increased dose of dupilumab | NR | upadacitinib 30 | |
| 46 | m | 21 | 50 | 1 | na | na | 22.5 | 4 | PR | Increased dose of dupilumab | NR | upadacitinib 30 | |||
| 47 | m | 31 | 80 | na | 29 | na | 4 | PR | Increased dose of dupilumab | CR | |||||
| 48 | f | 15 | 64 | 1 | 1 | na | na | na | 3 | PR | Combination of dupilumab with MTX | PR | |||
m male, f female, na data not available, CR complete or almost complete response, PR partial response, NR no response, CsA cyclosporin A, MTX methotrexate, ITRA itraconazole, M month, JAKi Janus Kinase inhibitors, HAND head and neck dermatitis, SCORAD scoring atopic dermatitis, EASI eczema area and severity index, IGA investigator's global assessment
Overall, 68.75% of the included patients achieved at least a PR, including 45.8% of CR. The mean duration of treatment was 5.8 months (range, 1–24). Increasing the dosage of dupilumab resulted in 14.3% of PR and 42.8% of CR. Combination with CsA resulted in 40% of PR and 60% of CR. Combination with MTX resulted in 28.6% of PR and 50% of CR. Combination with ITRA resulted in 25% of PR and 37.5% of CR.
Age, gender, weight, or severity scores (IGA, DLQI) before dupilumab first initiation did not influence the response. However, patients showing an initial NR never achieved a CR to further options (versus 52.4% of patients with an initial PR, p = 0.025) (Table S2).
Three patients discontinued combination therapy due to adverse events including drug-induced colitis and digestive intolerance with MTX (n = 1), digestive intolerance with ITRA (n = 1) and an episode of tachycardia with ITRA (n = 1). Of these, only 1 had achieved a CR to the additional MTX and was subsequently treated with a JAKi.
Discussion
In this French retrospective multicentric study of 48 AD patients with an inadequate response after 3 months of dupilumab 300mg/2weeks, up to 45.8% of the patients achieved a CR to alternative regimen maintaining dupilumab, either increasing its dose or combining with MTX, CsA or ITRA, though none proved significantly better. Digestive intolerance and tachycardia led to treatment discontinuation in 3 patients with MTX and ITRA.
In NR patients after 3 months of dupilumab 300mg/2weeks, no further CR could be achieved after 3 months of any alternative regimen, and a PR could be achieved in only half of them. This result may prompt for an earlier-than-6-months switch of dupilumab towards alternative treatments like JAKi. Indeed, a maintained but no additional efficacy of dupilumab was shown after 16 weeks in long-term studies.1
Patients prescribed with a combination therapy of dupilumab and CsA showed at least a PR and no adverse effects in a short-term follow-up. CsA had already been prescribed in these 5 patients prior to dupilumab, according with on-label use of dupilumab in France, and had been interrupted because of PR or NR and/or clinical or biological adverse effects. In a recent drug survival study, only 16% of AD patients discontinued CsA because of adverse effects, none of them serious.7 Moreover, adding CsA might reduce dupilumab-induced conjunctivitis. However, the duration of CsA treatment should not be over 1 year; thus the combination of dupilumab and MTX could be an interesting alternative, even in patients who had shown a PR or NR to MTX prior to dupilumab. Interestingly, out of the 5 patients previously prescribed with MTX prior to dupilumab, 2 had a CR with the combination of dupilumab with MTX, 2 showed NR and 1 had digestive adverse effects. This result is in line with a previous study showing that MTX was efficient and well tolerated in AD patients.8 However, the combination of dupilumab and MTX in our study was prescribed in patients with a lower mean EASI score (see Table S1: 11.7 vs 13.5 to 33, p = 0.02). This result suggests that this combination could rather be proposed to patients with milder disease. The combination of dupilumab with ITRA was almost exclusively proposed to patients with de novo or worsening dupilumab-associated HAND, according to the results of a previous study.9 Despite an acceptable PR and CR rate of 62.5% in our study, a recent study10 showed that patients prescribed with such a combination achieved a shorter and less good response than those prescribed with a JAKi treatment. Increasing the dose of dupilumab by narrowing the time interval between injections showed at least a PR in 57.1% of patients, almost exclusively in patients with an initial PR to dupilumab 300mg/2weeks. This result is not different from the other therapeutic options combining dupilumab with MTX, CsA or ITRA, but it dramatically increases costs.
In this study, no combination therapy of dupilumab with JAKi was reported. Such a combination was rarely reported in the literature,11 although achieving a better response in severe AD patients than the combination of dupilumab with CsA or systemic steroids.4
Limitations of this study include small sample size and a retrospective nature. The so-called “end-of-dose” effect, which refers to the relapse of pruritus or AD skin lesions shortly before next administration of dupilumab, was not assessed in this study, although it may be predictive of a better response to the narrowing of injections interval. Also the occurrence of a dupilumab-induced conjunctivitis was not under the scope of our study, while it could have altered the practicians’ decision to choose combination therapy over increasing the dose of dupilumab, despite a previous study reported a similar rate of adverse events between weekly versus every-two-weeks injections.12 The data in this study were mostly collected before the wide use of JAKi in AD in France, and the latter have dramatically modified the management of AD patients, providing a strict monitoring of their contraindications and adverse effects.
Conclusion
This retrospective study suggests that increasing the dose of dupilumab or combining dupilumab with CsA, MTX or ITRA may be safe options prior to a switch toward JAKi or in case of their contraindication. Additional treatments may be chosen upon particular phenotypes of AD or adverse effects of dupilumab monotherapy, such as HAND. Further studies are necessary to determinate the most favorable patients’ profiles for each option and evaluate their comparative costs.
Abbreviations
AD, atopic dermatitis; CsA, cyclosporin A; DLQI, dermatology life quality index; EASI, eczema area and severity index; HAND, head and neck dermatitis; IGA, investigator's global assessment; ITRA, itraconazole; JAKi, Janus Kinase inhibitors; MTX, methotrexate; SCORAD, Scoring atopic dermatitis.
Funding
No funding sources supported this work.
Data availability statement
All data are available upon reader's request to the corresponding author.
Authors contribution
R Strizzolo made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafted the article; gave final approval of the version to be published.
J Seneschal made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
A Soria made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
D Staumont-Sallé made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
S Barbarot made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
M Viguier made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
M Jachiet made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
A Nosbaum made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
A Clément made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
M Tauber made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revised the article critically for important intellectual content; gave final approval of the version to be published.
S Mallet made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; revising the article critically for important intellectual content; gave final approval of the version to be published.
A Du-Thanh made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafted the article and revised it critically for important intellectual content; gave final approval of the version to be published.
Ethics statement
This study was approved by the Montpellier University institutional review board (IRB-MTP_2023_04_202100936).
Authors’ consent for publication
I, the corresponding author, on behalf of all my co-authors, confirm our consent for publication.
Confirmation of unpublished work
This manuscript is original, has not been published before, is not currently being considered for publication elsewhere.
Declaration of competing interest
R Strizzolo reports no competing interest.
J Seneschal reports the following competing interests: Principal investigator or consultant or speaker for AbbVie, Almirall, Lilly, Sanofi, LeoPharma, Pierre Fabre, Pfizer; support for attending meetings from AbbVie.
A Soria reports the following competing interests: Consultant or speaker for Novartis, Sanofi, LEO Pharma, Abbvie, Lilly, Pfizer and Bioprojet
D Staumont-Sallé reports the following competing interests: Investigator, consultant and/or speaker for AbbVie, Almirall, Amgen, Astra-Zeneca, Eli Lilly, Galderma, Leo Pharma, Novartis, Pfizer, Sanofi-Regeneron, UCB.
S Barbarot reports the following competing interests: principal investigator, speaker and consultant: Astrazeneca, Almirall, Sanofi-Genzyme, Abbvie, Galderma, Alexion, Novartis, Janssen, Leo-Pharma, Pfizer, Eli Lilly, UCB Pharma, Chiesi.
M Viguier reports the following competing interests: travel fees, speaker, consultant and/or board member for Lilly, Abbvie, Janssen-Cilag, Galderma, Boehringer Ingelheim, Novartis, UCB, Nordic, Medac, Bristol Myers Squibb.
M Jachiet reports the following competing interests: investigator, consultant and/or speaker for AbbVie, Eli Lilly, Galderma, Leo Pharma, Pfizer, Sanofi-Regeneron.
A Nosbaum reports the following competing interests: investigator, consultant and/or speaker for AbbVie, Leo Pharma, Pfizer, Sanofi, Lilly, Medac.
A Clément reports the following competing interests: principal investigator, speaker and/or consultant for LeoPharma, Sanofi-Regeneron, Abbvie, Lilly, Janssen.
M Tauber reports the following competing interests: principal investigator, speaker and/or consultant for LeoPharma, Sanofi-Regeneron, Abbvie, Lilly, Medac, Almirall, Jenssen, Pfizer.
S Mallet reports the following competing interests: principal investigator or sub investigator for Lilly, Sanofi, LeoPharma, consulting fees from Lilly, Sanofi, LeoPharma, Pfizer, speaker for Lilly, Sanofi, LeoPharma, Pfizer, support for attending meetings Lilly, Sanofi, LeoPharma, participation on advisory board: Sanofi, LeoPharma, Pfizer.
A Du-Thanh reports the following competing interests: principal investigator, speaker and consultant for LeoPharma, Sanofi, Pfizer, Abbvie, Lilly.
Acknowledgments
To Pr Olivier Chosidow for his advice about the manuscript writing.
Footnotes
Full list of author information is available at the end of the article
Supplementary data to this article can be found online at https://doi.org/10.1016/j.waojou.2024.100923.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
References
- 1.Blauvelt A., de Bruin-Weller M., Gooderham M., et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet Lond Engl. 2017;389:2287–2303. doi: 10.1016/S0140-6736(17)31191-1. [DOI] [PubMed] [Google Scholar]
- 2.Faiz S., Giovannelli J., Podevin C., et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J Am Acad Dermatol. 2019;81:143–151. doi: 10.1016/j.jaad.2019.02.053. [DOI] [PubMed] [Google Scholar]
- 3.Gori N., Chiricozzi A., Malvaso D., et al. Successful combination of systemic agents for the treatment of atopic dermatitis resistant to dupilumab therapy. Dermatol Basel Switz. 2021;237:535–541. doi: 10.1159/000512890. [DOI] [PubMed] [Google Scholar]
- 4.Yang N., Chen L., Shao J., Jiang F., Liu J., Li Z. Dupilumab with concomitant Janus kinase inhibitor: a novel treatment strategy for atopic dermatitis with poor response to dupilumab. Br J Dermatol. 2022;187:828–830. doi: 10.1111/bjd.21776. [DOI] [PubMed] [Google Scholar]
- 5.Hendricks A.J., Lio P.A., Shi V.Y. Management recommendations for dupilumab partial and non-durable responders in atopic dermatitis. Am J Clin Dermatol. 2019;20:565–569. doi: 10.1007/s40257-019-00436-8. [DOI] [PubMed] [Google Scholar]
- 6.Narla S., Silverberg J.I., Simpson E.L. Management of inadequate response and adverse effects to dupilumab in atopic dermatitis. J Am Acad Dermatol. 2022;86:628–636. doi: 10.1016/j.jaad.2021.06.017. [DOI] [PubMed] [Google Scholar]
- 7.Law Ping Man S., Bouzillé G., Beneton N., Safa G., Dupuy A., Droitcourt C. Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporine. J Eur Acad Dermatol Venereol JEADV. 2018;32:1327–1335. doi: 10.1111/jdv.14880. [DOI] [PubMed] [Google Scholar]
- 8.Goujon C., Viguier M., Staumont-Sallé D., et al. Methotrexate versus cyclosporine in adults with moderate-to-severe atopic dermatitis: a phase III randomized noninferiority trial. J Allergy Clin Immunol Pract. 2018;6:562–569.e3. doi: 10.1016/j.jaip.2017.07.007. [DOI] [PubMed] [Google Scholar]
- 9.Soria A., Du-Thanh A., Seneschal J., et al. Development or exacerbation of head and neck dermatitis in patients treated for atopic dermatitis with dupilumab. JAMA Dermatol. 2019;155:1312–1315. doi: 10.1001/jamadermatol.2019.2613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kozera E., Flora A., Stewart T., et al. Dupilumab-associated head and neck dermatitis resolves temporarily with itraconazole therapy and rapidly with transition to upadacitinib, with Malassezia-specific immunoglobulin E levels mirroring clinical response. J Am Acad Dermatol. 2023;88:255–257. doi: 10.1016/j.jaad.2022.05.021. [DOI] [PubMed] [Google Scholar]
- 11.Peterson D.M., Vesely M.D. Remission of severe atopic dermatitis with dupilumab and rescue tofacitinib therapy. JAAD Case Rep. 2021;10:4–7. doi: 10.1016/j.jdcr.2021.01.020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Worm M., Simpson E.L., Thaçi D., et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156:131–143. doi: 10.1001/jamadermatol.2019.3617. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Data Availability Statement
All data are available upon reader's request to the corresponding author.