A 3-Year Experience with Tildrakizumab Treatment for Patients with Plaque Psoriasis in Clinical Practice

Abstract

Introduction

The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world.

Methods

This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included.

Results

One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful.

Conclusion

This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

Key Summary Points

The reappraisal of prolonged experiences with tildrakizumab in the clinical practice helps to optimize its use.

A long-term retrospective observational study in a real-life setting reported the efficacy in 136 adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab.

Psoriasis Area Severity Index (PASI100) was reached by 4 weeks in > 20% of cases and by 4 months in > 50% and remained between 70% and 80% from week 36 to 3 years.

We observed that those with a short history of psoriasis had a higher probability of PASI90 or PASI 100 within 36 weeks, suggesting that early treatment could be useful.

Introduction

Tildrakizumab is a high-affinity humanized monoclonal IgGk anti-IL-23p19 antibody approved in Europe and the USA for the first-line treatment of moderate-to-severe chronic plaque psoriasis in adults [1]. The recommended dose is 100 mg administered on weeks 0 and 4 and every 12 weeks thereafter. A 200-mg dose can be used as per the clinician's decision in patients with body weight > 90 kg or high burden of disease.

After the registration based on results from the randomized clinical studies reSURFACE 1 and reSURFACE 2 [2], the optional long-term extensions of both studies reported that the efficacy of tildrakizumab in responders at week 28 was maintained at 5 years of continued treatment [3]. Such results indicated the suitability of tildrakizumab for the prolonged treatment of plaque psoriasis as a chronic disease needing lifetime management.

Once efficacy and safety had been stated, the reappraisal of prolonged experiences in clinical practice was necessary to optimize the use of this pharmacological tool with less stringent selection criteria than in randomized controlled studies. Indeed, a first retrospective study on patients with moderate-to-severe plaque psoriasis in a real-life setting was published by our group shortly after the introduction of tildrakizumab in Italy [4], confirming the efficacy of the drug in the short term. Several other observations in clinical practice were then published. A Spanish study confirmed the efficacy of tildrakizumab at 24 weeks of treatment without correlation with prior treatments with biologics [5]. In Germany, the multicenter, prospective TILOT study found high effectiveness and a good safety profile over 52 weeks of treatment and, in addition, showed that good results could be obtained in patients with nail psoriasis and pruritus [6]. An Italian multicenter retrospective study, including 237 consecutive patients followed up to week 52, observed similar rates of 75% Psoriasis Area Severity Index (PASI75) and 90% PASI reduction (PASI90) responses and higher percentages of patients achieving 100% PASI reduction (PASI100) compared to the phase III clinical trials; an improved response was observed in patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities [7, 8].

As studies in the real-life setting presented observations either in the short-term or within 1 year [4, 7, 9, 10], we describe in this article the clinical response to tildrakizumab in adults with moderate-to-severe chronic plaque psoriasis over a 3-year period, observed in the setting of the clinical practice.

Methods

Adult patients with moderate-to-severe plaque psoriasis [body surface area involvement ≥ 10%, Physician Global Assessment (PGA) score ≥ 3 and PASI score ≥ 12] at baseline, eligible for systemic therapy and administered 100 mg tildrakizumab (at the time of study initiation, 200 mg tildrakizumab was not reimbursed) at weeks 0 and 4 and then every 12 weeks by subcutaneous injection, were included in the study. Eligible patients did not receive any concomitant systemic therapy with tildrakizumab. Pregnant women and subjects incompetent to release an informed consent were excluded. According to current clinical practice, this treatment was performed as recommended by local regulation. The patients were referred to the Dermatology Departments of Policlinic San Martino Hospital, IRCCS, Genova, Italy, between March 2020 and September 2023. Data were censored in October 2023.

Patients were assessed at baseline, weeks 4, 16, 36 and 52, and subsequently once a year, by a clinical visit and recordings of PASI and Dermatology Life Quality Index (DLQI). All subjects provided informed written consent prior to enrollment in the study. All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments. The present study was approved by the ethics committee of Ospedale Policlinico San Martino-IRCCS, Genova, Italy (study number 163/2023; protocol: Pubb_Pso_Burlando; Study ID: 10529). All subjects gave consent to participate. Participants gave consent to the publication of anonymous data.

Statistical Analysis

Demographic data were summarized by descriptive analysis. Normal distribution for continuous variables was checked by Shapiro-Wilk test. Means and standard deviations (SDs) were calculated for continuous variables, while absolute values and frequency (%) were calculated for categorical variables. The proportion of patients with PASI reduction was shown, and chi-square analysis was performed to compare the proportion of patients with PASI reduction between two groups of patients (disease duration > or ≥ 10 years, naïve vs bio-experienced patients). Binary logistic regression was performed to estimate baseline characteristics on percentage PASI reduction at different time points. The last observation carried forward (LOCF) imputation method was used to account for missing data. All analyses were performed with MedCalc^® Statistical Software version 22.021.

Results

Demographic and Clinical Data at Baseline

Overall, 136 patients were included; demographic and clinical data at baseline are reported in Table 1. The mean age was 57.3 ± 15.9 years; the number of males was 78 (57.4%). The mean age at the diagnosis of plaque psoriasis was 36.1 ± 18.3 years, and treatment with tildrakizumab started at the mean age of 55.2 ± 15.6 years. The mean body weight was 77 ± 15.4 kg, and 16 subjects had a weight > 90 kg. At baseline, 51 (37.5%) patients were affected by hypertension, 27 (19.9%) had hyperlipidemia, and 26 (19.1%) were obese.

Table 1.

Demographic and clinical data at baseline and previous therapies for plaque psoriasis (n = 136)

Demographic and clinical data	Mean ± SD or n (%)
Age (years)	57.3 ± 15.9
Age at psoriasis onset	36.1 ± 18.3
Age at tildrakizumab onset	55.2 ± 15.6
Weight (kg)	77.0 ± 15.4
Body mass index (kg/m2)	26.6 ± 5.1
Sex
Male	78 (57.4%)
Female	58 (42.6%)
Comorbidities
Obesity	26 (19.1%)
Diabetes	15 (11.0%)
Hyperlipidemia	27 (19.9%)
Hypertension	51 (37.5%)
Other	59 (43.4%)
Previous systemic therapies
Naïve for systemic therapies	6 (4.4%)
Ciclosporin	41 (30.1%)
Metotrexate	70 (51.5%)
UVA	4 (2.9%)
UVB	4 (2.9%)
Acitretin	11 (8.1%)
Dimethyl fumarate	19 (14.0%)
Previous biologic therapies
Naïve for biologic therapies	114 (83.8%)
Failure of previous biologic therapies	22/136 (16.1%) 22/22 (100%)
Adalimumab	11 (8.1%)
Brodalumab	4 (2.9%)
Certolizumab	1 (0.7%)
Etanercept	5 (3.7%)
Infliximab	4 (2.9%)
Ixekizumab	5 (3.7%)
Secukinumab	2 (1.5%)
Ustekinumab	2 (1.5%)

SD standard deviation

Most patients had classically localized psoriasis; the genital area was involved in 15 (11.0%) subjects, and palmoplantar disease was present in 14 (10.3%) patients.

Only 6 (4.4%) patients had not been treated for psoriasis before baseline, and 114 (83.8%) were naïve to treatment with biologic agents. All 22 patients who had received prior biologic agents were shifted to tildrakizumab after the failure of such an agent. Previous systemic therapies are reported in Table 1. The shorter duration of treatment was 21 months.

Outcomes of Treatment with Tildrakizumab

Figure 1 shows PASI reduction at study time points. As the number of evaluable patients reduced during the follow-up, the LOCF had comparable proportions at different time points. We observed that by week 36 of treatment, 100/120 (83.3%) patients reached PASI75, and 101/120 (84.2%) of subjects reached it by 3 years. PASI90 was reached by 82/120 (68.3%) patients at week 36 and by 84/120 (70.0%) after 3 years, PASI100 by 81/120 (67.5%) at week 36 and by 78/120 (65.0%) after 3 years.

Fig. 1.

Proportion of patients with PASI reduction (PASI75, PASI90 and PASI100) and patients with PASI < 2 at each control visit. PASI Psoriasis Area Severity Index

A logistic regression model was used to evaluate factors associated with PASI90 at study time points. A baseline lower PASI value was significantly associated with PASI90 at week 4 (p < 0.001). At week 16, disease duration < 10 years was positively associated with PASI90 (p = 0.03), and a trend was observed at week 36 (p = 0.051). Later, from 1 year to 3 years of treatment, there is no indication that any factor is associated to PASI90.

Indeed, at week 16, PASI90 was observed in 22/32 (68.7%) patients with < 10 years of psoriasis and 42/87 (48.3%; p = 0.048) patients with > 10 years of psoriasis. At week 36, PASI90 was observed in 25/32 (78.1%) patients with < 10 years psoriasis and 59/87 (67.8%; p = 0.276) patients with > 10 years psoriasis; additionally, PASI100 was observed in 25/32 (78.1%) patients with < 10 years psoriasis and 58/87 (66.7%; p = 0.230) patients with > 10 years psoriasis. Later, from 1 year to 3 years of treatment, the probability of obtaining a high PASI reduction was similar, independent of the length of the disease (Table 2).

Table 2.

Patients with PASI90 and PASI100 by disease duration either < 10 years or ≥ 10 years

Study timepoint	Disease duration, n of patients/evaluated patients (%)		p-value
	< 10 years	≥ 10 years
PASI90
4 weeks	9/32 (28.1%)	17/87 (19.5%)	0.317
16 weeks	22/32 (68.7%)	42/87 (48.3%)	0.048
36 weeks	25/32 (78.1%)	59/87 (67.8%)	0.276
1 year	23/32 (71.9%)	55/87 (63.2%)	0.380
2 years	25/32 (78.1%)	57/87 (65.5%)	0.190
3 years	25/32 (78.1%)	59/87 (67.8%)	0.276
PASI100
4 weeks	9/32 (28.1%)	17/87 (19.5%)	0.317
16 weeks	21/32 (65.6%)	41/87 (47.1%)	0.075
36 weeks	25/32 (78.1%)	58/87 (66.7%)	0.230
1 year	22/32 (68.7%)	54/87 (62.1%)	0.503
2 years	23/32 (71.9%)	54/87 (62.1%)	0.323
3 years	22/32 (68.7%)	56/87 (64.4%)	0.657

PASI Psoriasis Area Severity Index

PASI was < 2 in 27/32 (84.4%) patients after 3 years and in > 50% of patients by week 16 and at all following controls (Table 3).

Table 3.

Patients with PASI < 2 by disease duration either < 10 years or ≥ 10 years

Study timepoint	Disease duration, n of patients/evaluated patients (%)		p-value
	< 10 years	≥ 10 years
Baseline	–	–	–
4 weeks	9/32 (28.1%)	17/87 (19.5%)	0.317
16 weeks	21/32 (65.6%)	43/87 (49.4%)	0.118
36 weeks	25/32 (78.1%)	61/87 (70.1%)	0.389
1 year	26/32 (81.2%)	58/87 (66.7%)	0.123
2 years	27/32 (84.4%)	61/87 (70.1%)	0.118
3 years	27/32 (84.4%)	62/87 (71.3%)	0.146

PASI Psoriasis Area Severity Index

The mean PASI score was 12.6 ± 4.9 (n = 134) at baseline, 5.6 ± 4.2 (n = 121) at week 4, 2.2 ± 3.1 at week 16, 1.5 ± 1.43.3 at week 36, 1.8 ± 4.0 at 1 year, 1.8 ± 4.1 2 years and 1.8 ± 4.1 at 3 years.

No difference was observed at any timepoint in the proportion of subjects with PASI reduction or PASI < 2 between the group naïve to biologic agents and the 22 patients who had received biologic agents before tildrakizumab.

No patient discontinued tildrakizumab because of adverse events. No new type of adverse event was observed compared to the literature.

Discussion

This retrospective observational study reports the long-term outcomes obtained in the real-life setting with tildrakizumab treatment in adult patients with moderate-to-severe plaque psoriasis. Overall, our observation was in agreement with the results of clinical trials showing that the response to treatment with tildrakizumab is maintained over a 3-year period [8]. Nevertheless, our results cannot be compared to those of the extension analyses of the clinical trials as these re-randomized only responders and did not evaluate a complete cohort in the long term [8]. We can only speculate that a less strict selection of patients, as necessary in clinical practice, may even favor favorable outcomes.

Although tildrakizumab was administered according to clinical practice regulations, six patients had not received previous systemic therapy. Indeed, these subjects started systemic treatment during the COVID-19 pandemic when the appropriate follow-up for immunosuppressive agents was not feasible; first-line tildrakizumab was prescribed as a safer intervention in those emergency conditions.

Indeed, in our cohort, PASI100 was reached by 21.7% of cases at 4 weeks of therapy, a proportion similar to the one previously observed in a smaller sample [4], by 51.2% of patients at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We believe that confirmation of the long-term duration of treatment efficacy in the real-life setting is of practical importance as plaque psoriasis is a chronic disease requiring prolonged lifelong treatment.

Additionally, the identification of subsets of patients with a high probability of either early or prolonged response would be useful to guide treatment decisions in the clinical practice to save costs and inefficient therapy in subgroups with a low probability of success. Duration of treatment with anti-IL-23 agents was shown to be long in a review by Rusiñol et al. [10]; a real-world retrospective study reported a median duration of treatment with guselkumab of 11 months [11], and another study reported survival in treatment at 12 months of 73% of patients for tildrakizumab [12], 81–100% for guselkumab [10] and 89.2–96.4% for risankizumab [10].

We had previously observed a better response to tildrakizumab by patients naïve to biologic treatment in a multicenter retrospective study compared to patients who had received a previous biologic agent [13]. The analysis presented here over a longer follow-up of our cohort was unable to confirm this result, suggesting that not only naïve patients but also those who experienced previous biological treatments may equally benefit from tildrakizumab. Our data may suggest that naïve patients have a high PASI reduction within 36 weeks of tildrakizumab more frequently than non-naïve patients, but the probability of excellent results in the long term is not impacted by previous biologic therapy. If this latter observation is confirmed, we should counsel patients who have failed previous biology treatments and switching to tildrakizumab to continue the new treatment for long periods even if short-term results are not fully satisfactory, expecting progressive, although slow, improvements and durable, although late, efficacy.

Conversely, we found some differences in response depending on the length of the disease. Patients who had a psoriasis history < 10 years had a greater probability of PASI90 and PASI100 within 36 weeks of treatment with tildrakizumab. This observation suggests that early treatment could be more efficient than the introduction of tildrakizumab after a prolonged disease; additionally, patients with a long history of psoriasis should be encouraged to adhere to prolonged treatment as, despite needing a long treatment, they have a high chance of good response in the long term, not differently from those with a short history. Our results could support the hypothesis currently investigated by the GUIDE study, based on a biological and pharmacological rationale, that response to treatment is obtained earlier in patients with psoriasis history < 2 years than in those with a history > 10 years [14].

Although 16 patients had a body weight > 90 kg, none required a high dose (200 mg) of tildrakizumab. So, the high dose is not often necessary, but clinicians have this option for patients with a high burden of disease and/or low performance.

Finally, although the number of patients with palmoplantar or genital area psoriasis was limited, we observed that tildrakizumab was efficacious and tolerated, suggesting that it can be a suitable treatment also in difficult-to-treat areas.

Treatment with tildrakizumab was equally tolerated during the 3 years of follow-up.

The strength of this study is the prolonged follow-up, to 3 years, in the setting of clinical practice. Its limitation is the retrospective design.

Conclusion

In conclusion, this long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

Author Contributions

Study conception and design: Martina Burlando; collection and interpretation of data: Martina Burlando, Ilaria Salvi, Emanuele Cozzani; manuscript drafting: Martina Burlando; approval to submit: Martina Burlando, Ilaria Salvi, Aurora Parodi, Emanuele Cozzani

Funding

Almirall S.p.A., Italy, funded the editorial assistance for manuscript drafting and publication costs.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

M. Burlando, A. Parodi and E. Cozzani acted as speaker and consultant for Abbvie, Janssen, Amgen, Novartis, Eli Lilly, UCB Pharma. I. Salvi has no conflicting interests.

Ethical Approval

All subjects provided informed written consent prior to enrollment in the study. All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments. The present study was approved by the ethics committee of Ospedale Policlinico San Martino-IRCCS, Genova, Italy (study number 163/2023; protocol: Pubb_Pso_Burlando; Study ID: 10529). All subjects gave consent to participate. Participants gave consent to the publication of anonymous data.