
==== Front
Dermatol Ther (Heidelb)
Dermatol Ther (Heidelb)
Dermatology and Therapy
2193-8210
2190-9172
Springer Healthcare Cheshire

39073712
1229
10.1007/s13555-024-01229-6
Brief Report
Comparison of Drug-Free Remission after the End of Phase III Trials of Three Different Anti-IL-23 Inhibitors in Psoriasis
Hsieh Chang-Yu
Hsu Francis Li-Tien
http://orcid.org/0000-0002-1498-1474
Tsai Tsen-Fang tftsai@yahoo.com

grid.19188.39 0000 0004 0546 0241 Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City, 100 Taiwan, Republic of China
29 7 2024
29 7 2024
9 2024
14 9 26072620
22 4 2024
2 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Introduction

Knowing the remission duration after biologics discontinuation in patients with psoriasis is important, especially when disease relapse is defined as the restart of systemic agents, because it also reflects the real-world clinical practice when topical treatment alone is not adequate for disease control, and a systemic treatment, including biologic, is needed. Biologics are currently indicated for patients with psoriasis who are candidates for systemic treatments.

Methods

We included 42 patients who were followed up with regularly after the end of risankizumab, guselkumab and mirikizumab trials and investigated the drug-free remission (DFR). A Kaplan–Meier survival analysis and Cox regression model were employed to identify the possible risk factors for relapse.

Results

Overall, 38/42 (90.5%) patients experienced relapses after discontinuing trial biologics during the follow-up period of at least 96 weeks and up to 227 weeks. In all patients with relapse, the median DFR was 104 days. Kaplan–Meier survival analysis revealed a significant 1-year drug-free survival (DFS) difference between risankizumab (Z) and guselkumab (T) + mirikizumab (M) (p = 0.0462). A difference in DFS curves was noted when patients were categorized by disease duration > or ≤ 2 years (p = 0.1577) and maintenance of a psoriasis area and severity index score (PASI) of 90 at the end of trials (p = 0.1177). Univariate Cox regression model identified that age [hazard ratio (HR) = 1.030 (1.000–1.060), p = 0.0467] and disease duration [HR = 1.046(1.009–1.084), p = 0.0134] were significantly associated with relapse risk. A risk model was established on the basis of multivariable Cox regression results. Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) = 0.82–3.23, p = 0.1809].

Conclusion

Types of biologics used, disease duration > or ≤ 2 years, and PASI 90 improvement at the end of trial affect the 1-year DFS after biologics discontinuation. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings.

Trial registration

ClinicalTrials.gov identifiers NCT02694523, NCT03047395, NCT02207224, NCT02576431, NCT03482011, and NCT03556202.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-024-01229-6.

Keywords

Biologics
Psoriasis
Remission duration
Drug-free survival
issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
==== Body
pmcKey Summary Points

Why carry out this study?	
Current data of drug-free remission (DFR) duration is mainly derived from clinical trials. However, both the treatment and drug-free periods were short according to the study designs.	
The definition of relapse after biologics discontinuation varies greatly. Our study defined relapse as the use of any systemic therapy, including acitretin, methotrexate, cyclosporine, phototherapy, or biologics, reflecting the real-world setting.	
The DFR potential risk factors predictive of relapse after risankizumab (Z), guselkumab (T), or mirikizumab (M) discontinuation were investigated.	
What was learned from the study?	
38/42 (90.5%) patients experienced relapse after discontinuing trial biologics during the follow-up period, and most (32/42, 76.2%) patients had relapses within the first year.	
Disease duration of less than 2 years, sustained psoriasis area and severity index score improvement > 90%, and the use of risankizumab are associated with better drug-free survival and lower relapse risk.	
A predicting model for relapse risk after IL-23 inhibitor discontinuation was developed. Risk value = 0.021038 * Age + 0.515628 * Biologic_type( Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The low-risk group [risk value < 1.5 (median)] had a non-significant higher relapse risk than the high-risk group (risk value > 1.5).	

Introduction

Psoriasis is an immune-mediated inflammatory disease, with a chronic relapsing–remitting course. Although IL-23 inhibitors’ potential disease-modifying effect has been suggested [1], most patients still suffer from relapses after drug discontinuation [2]. The relapse of psoriasis is associated with tissue resident memory T (Trm) cell repopulation [3]. Current data of drug-free remission (DFR) duration is mainly derived from clinical trials, in which patients who achieved the primary endpoints between 24 and 28 weeks discontinued the treatment, and retreatment was not given until relapse or the open-label extension periods ~1–1.5 years later. However, both the treatment and drug-free periods were short according to the study designs [4], and patients were followed for only about 4 weeks after the end of studies. Moreover, the definition of relapse varied.

In real-world practice and various treatment consensuses, the treatment choices for psoriasis should be individualized [5] and based on disease severity, stability, and locations as well as quality of life. Patients with either extensive or unstable psoriasis were usually treated with oral systemic agents, phototherapy, or biologics when topical treatment alone was inadequate to control their disease. In fact, biologics are currently indicated for patients with psoriasis who are candidates for systemic treatment, although biologics in pivotal studies included only patients with moderate to severe psoriasis, defined as a body surface area (BSA) at least 10% and psoriasis area and severity index score (PASI) greater than 10 or 12. We, hereby, defined relapse as the initiation of any systemic treatment or biologics and investigated the DFR after biologics discontinuation of patients from three different IL-23 inhibitor trials who received either risankizumab (Z) (up to 6 years), guselkumab (T) (up to 5 years), or mirikizumab (M) (up to 3 years). The aim of current study is to determine the DFR after biologics discontinuation and identify potential risk factors predictive for relapse.

Methods

A total of 48 Taiwanese patients from our hospital who participated in the IMMVENT (NCT02694523) + LIMITLESS (NCT03047395; risankizumab, Z), VOYAGE1 (NCT02207224) + NAVIGATE (NCT02576431; guselkumab, T), and OASIS1 (NCT03482011) + OASIS3 (NCT03556202; mirikizumab, M) studies was screened. Six patients were excluded from the analysis due to being lost to follow-up (N = 3) or using self-pay biologics immediately after the end of trials (N = 3). In all, 21 patients from the risankizumab trials, 13 patients from the guselkumab trials, and 8 patients from the mirikizumab trials were included for final analysis. All patients were IL-23 inhibitor naïve and received monotherapy during the trials according to the protocols. Psoriasis relapse was defined as the use of any systemic therapy, including acitretin, methotrexate, cyclosporine, and phototherapy, or the use of biologics. In Taiwan, biologics are reimbursed for patients with psoriasis with PASI ≥ 10 who have failed at least two systemic agents in addition to phototherapy, each for at least 12 weeks. The severity of psoriasis was evaluated each time the patients came to the clinic by the same dermatologist.

Kaplan–Meier survival analysis was employed to estimate the relapse events and DFS after biologics discontinuation. Kaplan–Meier curves were compared by log-rank test. The DFR was calculated starting from the next scheduled injection time of each biologic, 8 weeks for guselkumab, 12 weeks for risankizumab, and 8 weeks for mirikizumab. Proportional hazard assumption was checked by Schoefled residuals. A Cox regression model was applied to estimate the hazard ratios of potential risk factors for relapse. In the present study, the least absolute shrinkage and selection operator (LASSO) method was used for variable selection in the multivariable Cox regression model. Risk value model was cross-validated by the leave-one-out method. Statistical analysis was conducted using SAS software (ver. 9.4). Categorical variables were presented as count and percentage. Continuous measures were presented as medians due to small sample size.

This study was conducted with the approval of institutional review board from National Taiwan University Hospital (201904124RINC). All included patients provided written consent for data collection. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Results

Overall Drug-Free Survival (DFS) and Drug-Free Remission (DFR)

All patients were followed up with for at least 96 weeks after the end of studies. The overall median follow-up time was 919 days. The median follow-up time was 679/1503/935 days after stopping risankizumab/guselkumab/mirikizumab, respectively, which corresponded to the date of last injection, till 18 March 2023. Overall, 38/42 (90.5%) patients experienced relapse after discontinuing trial biologics during the follow-up period. In all patients with relapse, the median DFR was 104 days. As most (32/42; 76.2%) patients had relapses within the first year (52 weeks) after drug discontinuation, our further calculation focused on the relapse rate in this period. Table 1 represents the baseline patient demographics. Patients with or without relapses within 52 weeks were well balanced.Table 1 Baseline patient demographics in patients with or without relapse

	Relapse	p-Valuea	
Yes (number and percentage)	No (number and percentage)	
n = 32	n = 10	
Age, median (IQR)	42.5 (24.5)	38.5 (20)	0.4967b	
Sex			0.6161	
 F	4 (12.50)	2 (20.00)		
 M	28 (87.50)	8 (80.00)		
Biologic type			0.4383	
 Z	14 (43.75)	7 (70.00)		
 T	11 (34.38)	2 (20.00)		
 M	7 (21.88)	1 (10.00)		
Biologic type			0.2772	
 Z	14 (43.75)	7 (70.00)		
 T + M	18 (56.25)	3 (30.00)		
Biologics naïvety			1.000	
 Yes	15 (46.88)	4 (40.00)		
 No	17 (53.13)	6 (60.00)		
Disease duration in years, median (IQR)	14.5 (12.5)	12 (7)	0.2490b	
Disease duration			0.1359	
  ≤ 2 years	1 (3.13)	2 (20.00)		
  > 2 years	31 (96.88)	8 (80.00)		
Maintenance of PASI 90 improvement at the end of trial			0.1520	
 PASI 90	13 (40.63)	7 (70.00)		
 PASI < 90	19 (59.38)	3 (30.00)		
 PASI 90 improvement at weeks 12–16			1.000	
 PASI 90	19 (59.38)	6 (40.63)		
 PASI < 90	13 (40.63)	4 (40.00)		
 Body weight (kg), median (IQR)	79.5 (25)	73.5 (18)	0.2615b	
Body weight			0.2842	
  ≤ 78 (mean) kg	15 (46.88)	7 (70.00)		
  > 78 kg	17 (53.13)	3 (30.00)		
Presence of psoriatic arthritis			0.7135	
 Yes	12 (37.50)	5 (50.00)		
 No	20 (62.50)	5 (50.00)		
Smoking			1.000	
 Yes	12 (37.50)	4 (40.00)		
 No	20 (62.50)	6 (60.00)		
IQR interquartile range, F female, M male, Z risankizumab, T guselkumab, M mirikizumab, PASI psoriasis area and severity index score

a Fisher exact test

b Mann–Whitney U test,

Biologics were reinitiated in 9/42 (21.4%) within 6 months, 17/42 (40.5%) within 1 year, and 29/41 (69%) within 2 years, respectively. After the discontinuation of biologics, the DFS at weeks 12, 24, 36, and 52 were 69.0%/42.9%/35.7%/23.8%, respectively (Fig. 1). Among those with relapse within 52 weeks, the median DFR was 94 days. For risankizumab, 14/21 (66.7%) patients had relapse within 52 weeks, and the median DFR was 102 days. For guselkumab, 11/13 (84.6%) patients had relapse within 52 weeks, and the median DFR was 49 days. For mirikizumab, 7/8 (87.5%) patients had relapse within 52 weeks, and the median DFR was 79 days.Fig. 1 Kaplan–Meier survival curve illustrating the overall drug-free survival after discontinuation of IL-23 inhibitors within 1 year

Kaplan–Meier Survival Analysis

Results of DFS difference by various grouping methods analyzed by Kaplan–Meier survival analysis are shown in Supplementary Table 1. A difference in 1-year DFS curves was found when patients were categorized by biologic types (p = 0.1151, Fig. 2A), disease duration > or ≤ 2 years (p = 0.1577, Fig. 2C), and maintenance of PASI 90 at the end of trials (p = 0.1177, Fig. 2D). Due to the similar survival curve morphology of guselkumab and mirikizumab (Fig. 2A) and the same dosing interval, we combined guselkumab and mirikizumab as a group and compared it with risankizumab, which revealed a significant 1-year survival difference (p = 0.0462, Fig. 2B).Fig. 2 Kaplan–Meier survival curves grouping by A type of biologic, B type of biologic, C disease duration > or ≤ 2 years, and (D) maintenance of PASI 90 improvement at the end of trial. MIRI mirikizumab, T guselkumab, Z risankizumab, TM guselkumab + mirikizumab, Z risankizumab, PASI psoriasis area and severity index score

Cox Regression Model

Proportional hazard assumption was checked by Schoefled residuals (age: p = 0.1196, biologic type: p = 0.3191, disease duration: p = 0.2577), and the results support the proportional hazard assumption. Results of univariate and multivariable Cox regression were listed in Table 2. The univariate Cox regression model showed age [hazard ratio (HR) = 1.030(1.000–1.060), p = 0.0467] and disease duration [HR = 1.046(1.009–1.084), p = 0.0134] were significantly associated with relapse risk. Biologic type [T + M versus Z; HR = 2.014 (0.995–4.076), p = 0.0516], failure to maintain PASI 90 improvement at the end of trial [HR = 1.746 (0.858–3.552), p = 0.1240] had a trend toward significance.Table 2 Univariable and multivariable Cox regression model

	Univariable hazard ratio (95% CI)	p-Value	Multivariable hazard ratio (95% CI)	p-Value	
Age (years)	1.030 (1.000–1.060)	0.0467	1.021 (0.988–1.056)	0.2183	
Sex					
 F	Ref				
 M	1.619 (0.567, 4.623)	0.3686			
Biologic type					
 Z	ref				
 T	1.849 (0.836, 4.092)	0.1292			
 M	2.35 (0.939, 5.88)	0.0679			
Biologic type					
 Z	Ref		Ref		
 T + M	2.014 (0.995, 4.076)	0.0516	1.675 (0.792–3.542)	0.1773	
Biologics naïvety					
 Yes	Ref.				
 No	0.799 (0.397, 1.611)	0.5313			
Disease duration (years)	1.046 (1.009–1.084)	0.0134	1.025 (0.985–1.068)	0.227	
 Disease duration ≤ 2 years	Ref.				
 Disease duration  > 2 years	3.787 (0.516, 27.811)	0.1905			
Maintenance of PASI 90 improvement at the end of trial					
 PASI ≥ 90	Ref.				
 PASI < 90	1.746 (0.858, 3.552)	0.1240			
PASI 90 improvement at week 12–16					
 PASI ≥ 90	Ref				
 PASI < 90	1.225 (0.603, 2.489)	0.5740			
 Body weight (kg)	1.013 (0.994–1.033)	0.1802			
Body weight					
  ≤ 78 kg	Ref.				
  > 78 kg	1.530 (0.761–3.076)	0.2322			
Presence of psoriatic arthritis					
 Yes	Ref.				
 No	1.105 (0.540–2.263)	0.7838			
Smoking					
 Yes	Ref.				
 No	0.997 (0.487–2.042)	0.9931			
Z risankizumab, T guselkumab, M mirikizumab, PASI psoriasis area and severity index, CI confidence interval

The identified variables according to the LASSO method include age, biologic type, and disease duration. Multivariable Cox regression model with adjustment of above variables was analyzed. A risk value model was established according to the coefficient of each variable in multivariable and cross-validated by the leave-one-out method. Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) 0.82–3.23, p = 0.1809]. Figure 3 illustrates the different survival curves in the high-risk and low-risk groups (p = 0.1749).Fig. 3 Kaplan–Meier survival curve grouping by median risk value (1.5). Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration

Discussion

Psoriasis is a chronic immune-mediated skin disease, and biologics, especially the IL-17 and IL-23 blockers, have become the standard of care for patients with moderate to severe psoriasis due to their high efficacy and relative safety demonstrated in randomized controlled trials. Temporary drug withdrawal in patients with good efficacy was also a part of some study designs to demonstrate the DFR and recapture rate of efficacy. However, the remission duration following the very end of the studies is not known, because patients were followed for only 4 weeks for safety reasons in pivotal studies. Ideally, patients with moderate to severe psoriasis need to be treated on a long-term basis, preferably uninterrupted. Nonetheless, in real-world practice [6] and after the end of studies, drug discontinuation is common or inevitable. Estimating the time to relapse is of clinical importance. In the current study, relapse is defined by using any systemic treatment or biologics to reflect the real-world setting. In fact, current biologics are also indicated for patients who are candidates for systemic treatment.

The definition of relapse following biologics discontinuation varies greatly, and a direct comparison between the trials is difficult. In pivotal trials, commonly used definitions of relapse include loss of PASI 90, loss of PGA 0 or 1, or 50% loss of maximum PASI improvement [4]. From the real-world evidence in Poland based on monitoring of therapeutic programs, the mean time to first relapse after biologics discontinuation was 276 days, and there is progressive shortening of remission duration in subsequent courses of biologic discontinuation [7]. In the IMMhance study, the median time to relapse after risankizumab discontinuation was 295 days [2]. In the interim analysis from the GUIDE study, the median treatment-free duration was 282 days for guselkumab [8]. The above values were numerically higher than that of our current study (169 days), which used a different definition of relapse.

Studies using the initiation of systemic therapy as a proxy of relapse similar to our study are scarce [8]. In a Spanish study from 12 hospitals using the same definition, duration for maintenance of response following drug discontinuation was 282 days for guselkumab (N = 33) and 192.5 days for secukinumab (N = 31) in those who finished the ECLIPSE study [8]. However, the duration was defined as the time between the last dose of the biologic and the start of a new systemic agent. Thus, it would be 226 days for guselkumab and 164.5 days for secukinumab using our definition. The shorter median DFR of our patients (risankizumab: 102 days; guselkumab: 49 days; mirikizumab: 79 days) may result from the more aggressive treatment altitudes of our physicians and patients. Alternatively, there might be a racial difference for the remission duration, knowing that Asian patients with psoriasis in pivotal trials of biologics typically had a shorter mean disease duration compared with Western patients, suggesting probably a faster disease progression [9, 10]. For example, this was 15.3 years for Asians and 18.2 years for non-Asians in the VOYAGE 1 and VOYAGE 2 studies [11] and 10–12 years for Asians [12] and 19.6 years for non-Asians [13] in the CLEAR study. Another possibility is the better patient accessibility to treatment. Because most trial patients were recruited from an existing patient pool in our clinic, the same study coordinator and dermatologist are available to all trial patients even after the end of studies in our site. In contrast, patients were sometimes recruited by outside contractors in some study sites. In addition, history of erythroderma was present in 7.1% (3/42) of our patients, which is higher than previous epidemiological study [14]. Patients with history of erythroderma were known to have a poorer drug survival and potentially a more unstable disease [15–17]. Finally, the follow-up period of the above trials covered the period of the coronavirus disease 2019 (COVID-19) pandemic and the popularity of COVID vaccination; both factors are known to induce psoriasis flare [18–21].

The 6-month DFS after biologic discontinuation in our study was 57.1% for risankizumab, 30.7% for guselkumab, and 25% for mirikizumab. This result was comparable to our previous study, in which the corresponding value was 29.2–66.7% depending on types of biologics [22]. The overall DFS in the current study was 24% at month 12, which is numerically higher than the 16.8% from our previous study on IL-17 inhibitors, TNF inhibitors, and tofacitinib [22]; the 12.6% from ustekinumab [23]; and the 20.8% from patients who withdrew from secukinumab trials [24], but lower than the 38% from the part 3 interim analysis of the GUIDE study [25] and the 50% from a large Danish nationwide study [26]. Biologics were reinitiated in 17/42 (40.5%) within 1 year and 29/41 (69%) within 2 years, respectively, which was similar to those (41.9% and 66.7%) in our previous studies for patients participating in non-IL-23 inhibitor trials. [22]

The great variability of relapse rate might result from the inconsistency in the definition of relapse and the different study designs. This might also be explained by various biologic types and the different treatment periods in these studies.

In fact, the Kaplan–Meier survival analysis revealed survival difference among these three biologics (Fig. 2A). Compared with guselkumab + mirikizumab, risankizumab had a significantly better 1-year DFS (p = 0.0462, Fig. 2B). Direct comparison of IL-23 inhibitors with regards to relapse events after biologic discontinuation is lacking, but risankizumab and guselkumab were reported to have a better drug survival [27, 28]. Systematic reviews showed similar efficacy between guselkumab and risankizumab [29, 30], and both appeared to effectively decrease Trm cells [31]. In addition to the intrinsic difference among three biologics, the 1-year DFS difference could also be attributed to the different treatment duration (6 versus 5 versus 3 years) on the basis of the trial designs. Further studies evaluating the influence of treatment duration on disease flare are warranted to confirm our hypothesis.

Despite the small number of our patients with a disease duration shorter than 2 years, we still identified the benefit of early intervention by Kaplan–Meier survival analysis and Cox regression model. Previously, a significant positive relationship was shown between the expression of Trm markers in patients with plaque psoriasis and the duration of skin lesions [32]. Trm may originate from Th17 and Treg cells [33]. Early intervention has been shown to effectively prevent Trm cell repopulation [34]. However, the definition of early intervention or short disease duration (SDD) varies among studies. In the STEPIn study, which aimed to investigate the benefit of early intervention of secukinumab, only patients with a disease duration of less than 1 year were included [35]. In the GUIDE study, patients with short duration (≤ 2 years) had a quicker and better response with longer drug-free remission duration [36]. In addition, those with SDD also had a faster normalization of Trm cell counts [37]. Our previous study also pointed out that disease duration ≤ 2 years is associated with a lower risk of relapse [22].

The mean disease durations of patients with psoriasis in clinical trials were also typically long, usually between ~14–20 years [9]. Despite the positive association with relapse and remission duration, the effect of disease duration does not usually affect the treatment efficacy or effectiveness in clinical trials. For example, in the PSoHO studies, there is no difference in treatment efficacy when using disease duration 15 years as a cut-off point [38]. Also, in the post hoc analysis of ECLIPSE study in Spain, SDD was defined as either 3 or 5 years, and only 3 years was correlated with longer DFR [8]. Thus, more aggressive treatments at early time points, possibly no later than 2 or 3 years, might be needed to capture the window of opportunity to modify the disease course. Nonetheless, as there are few patients with moderate to severe psoriasis that have SDD in both real-world experience and clinical trials, more work is needed to verify the impact of disease duration on DFR.

Time to achieve PASI 50 response was a significant predictor for time to relapse in those stopping ustekinumab [23]; nonetheless, our study failed to demonstrate the link between rapid improvement (such as achievement of PASI 90 at week 12–16; p = 0.5715 by Kaplan–Meier test) with DFS. Instead, the sustainability, that is, the maintenance of PASI 90 at the end of trial was associated with better 1-year DFS when analyzed by log-rank test (p = 0.1177, Fig. 2D). This finding is consistent with previous articles in which PASI at the last follow-up visit [7] and PASI improvement [22] are risk factors for relapse. Prior study of ustekinumab also showed positive correlation of maximum PASI improvement and time to relapse [23]. A large nationwide cohort study found a numerically higher rate of re-starting systemic agents at month 12 in those with PASI > 0 at discontinuation compared with those with PASI = 0 [26].

Although biologics naïvety was suggested as a predictor for better relapse-free survival [7, 22], our study failed to demonstrate similar results. Since all our patients from the studies were IL-23 inhibitor naïve, it might be explained by the relative lack of influence on the effectiveness of IL-23 inhibitors in patients treated by prior non-IL-23 inhibitors as revealed by a previous study [39]. Similar to our findings, another retrospective analysis of Spanish patients who completed the ECLIPSE study also showed that prior biologics did not influence the time to relapse after withdrawal from guselkumab or secukinumab [8].

The key limitation is the small patient numbers due to a single-center experience. However, the single-center, same-evaluator design also has the advantage of consistent treatment altitude and efficacy assessment. Another limitation is the lack of stringent criteria for relapse compared with the designs in pivotal studies. However, current study is a reflection of real-world practice, in which patients who cannot be adequately controlled with topical treatment alone are candidates for systemic treatment or biologics.

Conclusions

In conclusion, 38/42 (90.5%) patients experienced relapse after discontinuing trial biologics during the median follow-up time of 919 days. The median DFR duration was 104 days with 32/42 (76.2%) relapses occurring within the first year. The DFR seemed to be shorter than a previous study using the same definition of relapse. However, the percentage of patients treated by next biologic is similar at 1 and 2 years (40.5% and 69%) compared with those participating in non-IL-23 inhibitor trials in a previous study. We further identified a 1-year DFS difference when categorizing patients by types of biologics used, disease duration > or ≤ 2 years, and PASI 90 improvement at the end of the trial. Early treatment and sustained improvement were associated with better DFS in several studies. However, it is unknown whether a longer treatment period can result in longer DFS possibly by a further decrease in Trm cells. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings and answer these unsolved questions.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (PDF 91 KB)

Acknowledgements

The authors would like to express gratitude to the staff of National Taiwan University Hospital—Statistical Consulting Unit (NTUH-SCU) for statistical consultation and analyses. The authors thank all the participants of this study.

Author Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Dr. Chang-Yu Hsieh collected patient data and drafted the manuscript. Francis Li-Tien Hsu collected and analyzed patient data. Dr. Tsen-Fang Tsai is responsible for the ideation of this topic and final refinement of this article.

Funding

No funding or sponsorship was received for this study or publication of this article.

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

Chang-Yu Hsieh received honoraria for educational events from Boehringer Ingelheim. Francis Li-Tien Hsu has no conflict of interest. Tsen-Fang Tsai has conducted clinical trials or received honoraria for serving as a consultant for Abbvie, AnaptysBio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, Galderma, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme, Novartis International, Pfizer, PharmaEssentia, Sanofi, Sun Pharma, and UCB Pharma. Tsen-Fang Tsai is an Editorial Board member of Dermatology and Therapy. Tsen-Fang Tsai was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethical Approval

This study was conducted with the approval of institutional review board from National Taiwan University Hospital (201904124RINC). All included patients provided written consent for data collection. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.
==== Refs
References

1. Bellinato F Chiricozzi A Piaserico S Targher G Gisondi P Could targeted pharmacotherapies exert a “disease modification effect” in patients with chronic plaque psoriasis? Int J Mol Sci 2022 23 12849 10.3390/IJMS232112849 36361639
Bellinato F, Chiricozzi A, Piaserico S, Targher G, Gisondi P. Could targeted pharmacotherapies exert a “disease modification effect” in patients with chronic plaque psoriasis? Int J Mol Sci. 2022;23:12849. 10.3390/IJMS232112849.36361639 10.3390/IJMS232112849
2. Blauvelt A Leonardi CL Gooderham M Papp KA Philipp S Wu JJ Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis: a phase 3 randomized clinical trial JAMA Dermatol 2020 156 649 658 10.1001/jamadermatol.2020.0723 32267471
Blauvelt A, Leonardi CL, Gooderham M, Papp KA, Philipp S, Wu JJ, et al. Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:649–58. 10.1001/jamadermatol.2020.0723.32267471 10.1001/jamadermatol.2020.0723
3. Tian D Lai Y The relapse of psoriasis: mechanisms and mysteries JID Innov 2022 2 100116 10.1016/j.xjidi.2022.100116 35601055
Tian D, Lai Y. The relapse of psoriasis: mechanisms and mysteries. JID Innov. 2022;2: 100116. 10.1016/j.xjidi.2022.100116.35601055 10.1016/j.xjidi.2022.100116
4. Masson Regnault M Shourick J Jendoubi F Tauber M Paul C Time to relapse after discontinuing systemic treatment for psoriasis: a systematic review Am J Clin Dermatol 2022 23 433 447 10.1007/s40257-022-00679-y 35489008
Masson Regnault M, Shourick J, Jendoubi F, Tauber M, Paul C. Time to relapse after discontinuing systemic treatment for psoriasis: a systematic review. Am J Clin Dermatol. 2022;23:433–47. 10.1007/s40257-022-00679-y.35489008 10.1007/s40257-022-00679-y
5. Silocchi L Damiani G Dermatological management in special population affected by psoriasis: a case report of an amputated transgender with psoriasis treated with apremilast Dermatol Sin 2023 41 38 39 10.4103/DS.DS-D-22-00096
Silocchi L, Damiani G. Dermatological management in special population affected by psoriasis: a case report of an amputated transgender with psoriasis treated with apremilast. Dermatol Sin. 2023;41:38–9. 10.4103/DS.DS-D-22-00096.10.4103/DS.DS-D-22-00096
6. Tada Y Soliman AM Ishii K Sakuma R Puig L Davis M Real-world discontinuation and switching patterns for interleukin-inhibitor treatments in patients with moderate-to-severe psoriasis in Japan Dermatol Ther (Heidelb) 2024 14 99 114 10.1007/S13555-023-01064-1/TABLES/3 38019410
Tada Y, Soliman AM, Ishii K, Sakuma R, Puig L, Davis M, et al. Real-world discontinuation and switching patterns for interleukin-inhibitor treatments in patients with moderate-to-severe psoriasis in Japan. Dermatol Ther (Heidelb). 2024;14:99–114. 10.1007/S13555-023-01064-1/TABLES/3.38019410 10.1007/S13555-023-01064-1/TABLES/3
7. Owczarek W Dzik M Narbutt J Walecka I Kowalczyk M Real-world evidence on time to relapse of plaque psoriasis after discontinuation of biologic treatment in Poland Dermatol Ther (Heidelb) 2021 34 e15052 10.1111/dth.15052
Owczarek W, Dzik M, Narbutt J, Walecka I, Kowalczyk M. Real-world evidence on time to relapse of plaque psoriasis after discontinuation of biologic treatment in Poland. Dermatol Ther (Heidelb). 2021;34: e15052. 10.1111/dth.15052.10.1111/dth.15052
8. Rivera R Martorell A López A Salgado L Sahuquillo A de la Cueva P Maintenance of response following discontinuation of guselkumab and secukinumab in Spanish patients who participated in the ECLIPSE study J Eur Acad Dermatol Venereol 2021 35 e65 e67 10.1111/JDV.16809 32648955
Rivera R, Martorell A, López A, Salgado L, Sahuquillo A, de la Cueva P, et al. Maintenance of response following discontinuation of guselkumab and secukinumab in Spanish patients who participated in the ECLIPSE study. J Eur Acad. 2021;35:e65–7. 10.1111/jdv.16809.32648955 10.1111/JDV.16809
9. Tsai Y-C Tsai T-F A review of clinical trials of biologic agents and small molecules for psoriasis in Asian subjects G Ital Dermatol Venereol 2016 151 412 431 26889727
Tsai Y-C, Tsai T-F. A review of clinical trials of biologic agents and small molecules for psoriasis in Asian subjects. G Ital Dermatol Venereol. 2016;151:412–31.26889727
10. Tsai T-F Yeh T-Y The use of biologics for psoriasis in Asia-Pacific Region Curr Rheumatol Rev 2009 5 149 152 10.2174/157339709789208615
Tsai T-F, Yeh T-Y. The use of biologics for psoriasis in Asia-Pacific Region. Curr Rheumatol Rev. 2009;5:149–52. 10.2174/157339709789208615.10.2174/157339709789208615
11. Reich K Song M Li S Jiang J Youn SW Tsai TF Consistent responses with guselkumab treatment in Asian and non-Asian patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2 J Dermatol 2019 46 1141 1152 10.1111/1346-8138.15109 31631377
Reich K, Song M, Li S, Jiang J, Youn SW, Tsai TF, et al. Consistent responses with guselkumab treatment in Asian and non-Asian patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2. J Dermatol. 2019;46:1141–52. 10.1111/1346-8138.15109.31631377 10.1111/1346-8138.15109
12. Lee MG Huang YH Lee JH Lee SC Kim TG Aw DCW Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: subgroup analysis from the CLEAR study J Dermatol 2019 46 752 758 10.1111/1346-8138.15004 31342560
Lee MG, Huang YH, Lee JH, Lee SC, Kim TG, Aw DCW, et al. Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: subgroup analysis from the CLEAR study. J Dermatol. 2019;46:752–8. 10.1111/1346-8138.15004.31342560 10.1111/1346-8138.15004
13. Thaçi D Blauvelt A Reich K Tsai TF Vanaclocha F Kingo K Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial J Am Acad Dermatol 2015 73 400 409 10.1016/j.jaad.2015.05.013 26092291
Thaçi D, Blauvelt A, Reich K, Tsai TF, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400–9. 10.1016/j.jaad.2015.05.013.26092291 10.1016/j.jaad.2015.05.013
14. Singh RK Lee KM Ucmak D Brodsky M Atanelov Z Farahnik B Erythrodermic psoriasis: pathophysiology and current treatment perspectives Psoriasis (Auckl) 2016 6 93 10.2147/PTT.S101232 28856115
Singh RK, Lee KM, Ucmak D, Brodsky M, Atanelov Z, Farahnik B, et al. Erythrodermic psoriasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:93. 10.2147/PTT.S101232.28856115 10.2147/PTT.S101232
15. Egeberg A Bryld LE Skov L Drug survival of secukinumab and ixekizumab for moderate-to-severe plaque psoriasis J Am Acad Dermatol 2019 81 173 178 10.1016/J.JAAD.2019.03.048 30914343
Egeberg A, Bryld LE, Skov L. Drug survival of secukinumab and ixekizumab for moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2019;81:173–8. 10.1016/J.JAAD.2019.03.048.30914343 10.1016/J.JAAD.2019.03.048
16. Chiu TS Tsai TF Treatment response in patients with moderate-to-severe psoriasis who had inadequate response to prior secukinumab Dermatol Sin 2019 37 129 133 10.4103/DS.DS_36_18
Chiu TS, Tsai TF. Treatment response in patients with moderate-to-severe psoriasis who had inadequate response to prior secukinumab. Dermatol Sin. 2019;37:129–33. 10.4103/DS.DS_36_18.10.4103/DS.DS_36_18
17. Weng HJ Wang TS Tsai TF Clinical experience of secukinumab in the treatment of erythrodermic psoriasis: a case series Br J Dermatol 2018 178 1439 1440 10.1111/BJD.16252 29265175
Weng HJ, Wang TS, Tsai TF. Clinical experience of secukinumab in the treatment of erythrodermic psoriasis: a case series. Br J Dermatol. 2018;178:1439–40. 10.1111/BJD.16252.29265175 10.1111/BJD.16252
18. Chao JP Tsai TF Psoriasis flare following ChAdOx1-S/nCoV-19 vaccination in patients with psoriasis under biologic treatment Dermatol Sin 2021 39 208 209 10.4103/DS.DS_45_21
Chao JP, Tsai TF. Psoriasis flare following ChAdOx1-S/nCoV-19 vaccination in patients with psoriasis under biologic treatment. Dermatol Sin. 2021;39:208–9. 10.4103/DS.DS_45_21.10.4103/DS.DS_45_21
19. Huang YW Tsai TF Exacerbation of psoriasis following COVID-19 vaccination: report from a single center Front Med (Lausanne) 2021 8 812010 10.3389/fmed.2021.812010 35004790
Huang YW, Tsai TF. Exacerbation of psoriasis following COVID-19 vaccination: report from a single center. Front Med (Lausanne). 2021;8: 812010. 10.3389/fmed.2021.812010.35004790 10.3389/fmed.2021.812010
20. Lin PT Chi CC Erythrodermic psoriasis following ChAdOx1 nCOV-19 vaccination: a case report Dermatol Sin 2022 40 62 63 10.4103/DS.DS_11_22
Lin PT, Chi CC. Erythrodermic psoriasis following ChAdOx1 nCOV-19 vaccination: a case report. Dermatol Sin. 2022;40:62–3. 10.4103/DS.DS_11_22.10.4103/DS.DS_11_22
21. Hsu YSO Tsai TF A case of new-onset palmoplantar pustulosis following mRNA COVID-19 vaccination Dermatol Sin 2023 41 127 128 10.4103/DS.DS-D-23-00004
Hsu YSO, Tsai TF. A case of new-onset palmoplantar pustulosis following mRNA COVID-19 vaccination. Dermatol Sin. 2023;41:127–8. 10.4103/DS.DS-D-23-00004.10.4103/DS.DS-D-23-00004
22. Huang YW Tsai TF Remission duration and long-term outcomes in patients with moderate-to-severe psoriasis treated by biologics or tofacitinib in controlled clinical trials: a 15-year single-center experience Dermatol Ther (Heidelb) 2019 9 553 569 10.1007/S13555-019-0310-5 31270683
Huang YW, Tsai TF. Remission duration and long-term outcomes in patients with moderate-to-severe psoriasis treated by biologics or tofacitinib in controlled clinical trials: a 15-year single-center experience. Dermatol Ther (Heidelb). 2019;9:553–69. 10.1007/S13555-019-0310-5.31270683 10.1007/S13555-019-0310-5
23. Chiu HY Hui RCY Tsai TF Chen YC Chang Liao NF Chen PH Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: an 8-year multicenter study J Am Acad Dermatol 2023 88 71 78 10.1016/J.JAAD.2019.01.035 30703455
Chiu HY, Hui RCY, Tsai TF, Chen YC, Chang Liao NF, Chen PH, et al. Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: an 8-year multicenter study. J Am Acad Dermatol. 2023;88:71–8. 10.1016/J.JAAD.2019.01.035.30703455 10.1016/J.JAAD.2019.01.035
24. Lebwohl M Iversen L Eidsmo L Krueger JG Suárez-Fariñas M Tomalin L Investigation of plaque psoriasis relapse after secukinumab withdrawal in patients from two phase III studies Clin Exp Dermatol 2023 10.1093/ced/llad329
Lebwohl M, Iversen L, Eidsmo L, Krueger JG, Suárez-Fariñas M, Tomalin L, et al. Investigation of plaque psoriasis relapse after secukinumab withdrawal in patients from two phase III studies. Clin Exp Dermatol. 2023. 10.1093/ced/llad329.10.1093/ced/llad329
25. Schäkel et al. Treatment-free period of more than 1 year in guselkumab super responders with short disease duration of psoriasis: withdrawal data from the GUIDE trial. 2023 EADV Congress, Berlin: 2023.
26. Luu Y Cheng A-L Reisz C Trajectories and prognosis after discontinuation of biologics due to remission in psoriasis: a nationwide cohort study J Am Acad Dermatol 2023 88 1378 1381 10.1001/jamadermatol 36739903
Luu Y, Cheng A-L, Reisz C. Trajectories and prognosis after discontinuation of biologics due to remission in psoriasis: a nationwide cohort study. J Am Acad Dermatol. 2023;88:1378–81. 10.1001/jamadermatol.36739903 10.1001/jamadermatol
27. Mastorino L Dapavo P Susca S Cariti C Siliquini N Verrone A Drug survival and clinical effectiveness of secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab for psoriasis treatment J Dtsch Dermatol Ges 2024 22 34 42 10.1111/DDG.15251 37926830
Mastorino L, Dapavo P, Susca S, Cariti C, Siliquini N, Verrone A, et al. Drug survival and clinical effectiveness of secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab for psoriasis treatment. J Dtsch Dermatol Ges. 2024;22:34–42. 10.1111/DDG.15251.37926830 10.1111/DDG.15251
28. Gargiulo L Ibba L Malagoli P Balato A Bardazzi F Burlando M Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses—IL PSO (Italian landscape psoriasis) Front Immunol 2024 11 1341708 10.3389/FIMMU.2023.1341708
Gargiulo L, Ibba L, Malagoli P, Balato A, Bardazzi F, Burlando M, et al. Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses—IL PSO (Italian landscape psoriasis). Front Immunol. 2024;11:1341708. 10.3389/FIMMU.2023.1341708.10.3389/FIMMU.2023.1341708
29. Yeh C-P Huang YW Tsai T-F Comparison of the relative efficacy of different biologics in different body areas in patients with moderate to severe psoriasis receiving biologics and tofacitinib in phase 3 randomized controlled trials: a 15-year single-center experience Expert Rev Clin Pharmacol 2022 15 887 895 10.1080/17512433.2022.2103538 35848067
Yeh C-P, Huang YW, Tsai T-F. Comparison of the relative efficacy of different biologics in different body areas in patients with moderate to severe psoriasis receiving biologics and tofacitinib in phase 3 randomized controlled trials: a 15-year single-center experience. Expert Rev Clin Pharmacol. 2022;15:887–95. 10.1080/17512433.2022.2103538.35848067 10.1080/17512433.2022.2103538
30. Ruggiero A Fabbrocini G Cinelli E Megna M Real world practice indirect comparison between guselkumab and risankizumab: results from an Italian retrospective study Dermatol Ther (Heidelb) 2022 35 e15214 10.1111/DTH.15214
Ruggiero A, Fabbrocini G, Cinelli E, Megna M. Real world practice indirect comparison between guselkumab and risankizumab: results from an Italian retrospective study. Dermatol Ther (Heidelb). 2022;35: e15214. 10.1111/DTH.15214.10.1111/DTH.15214
31. Blauvelt A Resident memory T cells in psoriasis: key to a cure? J Psoriasis Psoriatic Arthritis 2022 7 157 159 10.1177/24755303221127338
Blauvelt A. Resident memory T cells in psoriasis: key to a cure? J Psoriasis Psoriatic Arthritis. 2022;7:157–9. 10.1177/24755303221127338.10.1177/24755303221127338
32. Kasprowicz-Furmańczyk M Czerwińska J Placek W Owczarczyk-Saczonek A Assessment of the tissue resident memory cells in lesional skin of patients with psoriasis and in healthy skin of healthy volunteers Int J Environ Res Public Health 2021 18 11251 10.3390/IJERPH182111251 34769769
Kasprowicz-Furmańczyk M, Czerwińska J, Placek W, Owczarczyk-Saczonek A. Assessment of the tissue resident memory cells in lesional skin of patients with psoriasis and in healthy skin of healthy volunteers. Int J Environ Res Public Health. 2021;18:11251. 10.3390/IJERPH182111251.34769769 10.3390/IJERPH182111251
33. Dong C Lin L Du J Characteristics and sources of tissue-resident memory T cells in psoriasis relapse Curr Res Immunol 2023 4 100067 10.1016/J.CRIMMU.2023.100067 37701270
Dong C, Lin L, Du J. Characteristics and sources of tissue-resident memory T cells in psoriasis relapse. Curr Res Immunol. 2023;4: 100067. 10.1016/J.CRIMMU.2023.100067.37701270 10.1016/J.CRIMMU.2023.100067
34. Vo S Watanabe R Koguchi-Yoshioka H Matsumura Y Ishitsuka Y Nakamura Y CD8 resident memory T cells with interleukin 17A-producing potential are accumulated in disease-naïve nonlesional sites of psoriasis possibly in correlation with disease duration Br J Dermatol 2019 181 410 412 10.1111/BJD.17748 30737771
Vo S, Watanabe R, Koguchi-Yoshioka H, Matsumura Y, Ishitsuka Y, Nakamura Y, et al. CD8 resident memory T cells with interleukin 17A-producing potential are accumulated in disease-naïve nonlesional sites of psoriasis possibly in correlation with disease duration. Br J Dermatol. 2019;181:410–2. 10.1111/BJD.17748.30737771 10.1111/BJD.17748
35. Iversen L Conrad C Eidsmo L Costanzo A Narbutt J Pinter A Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study J Eur Acad Dermatol Venereol 2023 37 1004 1016 10.1111/jdv.18846 36606536
Iversen L, Conrad C, Eidsmo L, Costanzo A, Narbutt J, Pinter A, et al. Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study. J Eur Acad Dermatol Venereol. 2023;37:1004–16. 10.1111/jdv.18846.36606536 10.1111/jdv.18846
36. Schäkel K Reich K Asadullah K Pinter A Jullien D Weisenseel P Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): Week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study J Eur Acad Dermatol Venereol 2023 37 2016 2027 10.1111/JDV.19236 37262309
Schäkel K, Reich K, Asadullah K, Pinter A, Jullien D, Weisenseel P, et al. Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): Week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study. J Eur Acad Dermatol Venereol. 2023;37:2016–27. 10.1111/JDV.19236.37262309 10.1111/JDV.19236
37. Angsana J Kohler K Sendecki J Leung MW Tabori S Krüger N Higher IL-10+ T cell and treg cell counts in psoriatic skin are associated with super-response to guselkumab: data from the phase 3 guide trial J Invest Dermatol 2023 143 S101 10.1016/J.JID.2023.03.594
Angsana J, Kohler K, Sendecki J, Leung MW, Tabori S, Krüger N, et al. Higher IL-10+ T cell and treg cell counts in psoriatic skin are associated with super-response to guselkumab: data from the phase 3 guide trial. J Invest Dermatol. 2023;143:S101. 10.1016/J.JID.2023.03.594.10.1016/J.JID.2023.03.594
38. Lynde C Riedl E Maul JT Torres T Pinter A Fabbrocini G Comparative effectiveness of biologics across subgroups of patients with moderate-to-severe plaque psoriasis: results at week 12 from the PSoHO study in a real-world setting Adv Ther 2023 40 869 886 10.1007/S12325-022-02379-9 36515803
Lynde C, Riedl E, Maul JT, Torres T, Pinter A, Fabbrocini G, et al. Comparative effectiveness of biologics across subgroups of patients with moderate-to-severe plaque psoriasis: results at week 12 from the PSoHO study in a real-world setting. Adv Ther. 2023;40:869–86. 10.1007/S12325-022-02379-9.36515803 10.1007/S12325-022-02379-9
39. Hsieh CY Tsai TF Effectiveness and safety of reduced-dose secukinumab switching to risankizumab for psoriasis patients in Asian population: a case series Exp Dermatol 2023 32 1048 1050 10.1111/EXD.14810 37032610
Hsieh CY, Tsai TF. Effectiveness and safety of reduced-dose secukinumab switching to risankizumab for psoriasis patients in Asian population: a case series. Exp Dermatol. 2023;32:1048–50. 10.1111/EXD.14810.37032610 10.1111/EXD.14810
