Biologics is used for treating moderate to severe plaque psoriasis (MSPP), which represent one of the foremost therapeutic advancements in disease of dermatology. Up to now, the relative efficacy and safety across approved andinvestigational biologics for MSPP is still unclear.
This study aimed to comparative effectiveness of various biological treatments for MSPP measured by PASI75, PASI90 and PASI100 (The ratio of patients whose Psoriasis Area and Severity Index score (PASI) decreased by ≥ 75%, 90% and 100% compared with baseline, respectively). In addition, random models were used together with a Bayesian method to compare direct and indirect Adverse Events (AEs) of biologics with placebo, to make probabilistic statements and predictions on their AEs. The analytic data set was made up of summarized data from 54 trials, including 27,808 patients, with treatment of 17 biologics. Three mathematic models with nonparametric placebo evaluations were established to characterize the longitudinal direction profile for the three efficacy measures as above mentioned.
Our results showed significant differences among treatments. Bimekizumab, sonelokimab, and ixekizumab were found to be the most effective treatments among the biologics. The effects of covariate were further evaluated, patients\' age, body weight, duration of disease and percentage of patients previously treated with a biological therapy showed impact on the efficacy. In addition, we found that ixekizumab and risankizumab displayed relatively stable as for efficacy and safety.
Our findings provide valuable insights into the comparative effectiveness and safety of biologics for MSPP treatment. These results may aid in clinical decision-making and ultimately improve patient outcomes.

Background: The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Methods: Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). Results: A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What\'s more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. Conclusions: This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.
METHODS: In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator\'s Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients\' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.
RESULTS: Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).
CONCLUSIONS: The results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.
BACKGROUND: Clinicaltrials.gov Identifier, NCT02826603.
BACKGROUND: Novartis Pharma AG, Basel, Switzerland.