Matching-adjusted indirect comparison (MAIC) of deucravacitinib versus adalimumab for the treatment of patients with moderate to severe plaque psoriasis over 2 years

Abstract

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in the US for the treatment of adults with moderate to severe plaque psoriasis (PsO). A previous indirect treatment study showed comparable efficacy between deucravacitinib and first-generation biologics at week 52. The objective of this study was to compare the long-term efficacy of deucravacitinib to that of adalimumab based on long-term extension (LTE) trials, after adjusting for differences in patient characteristics at baseline. 
 Methods: Open-label LTE trials that were feasible for indirect treatment comparison were identified for each treatment (deucravacitinib: POETYK PSO-LTE [NCT04036435]; adalimumab: REVEAL extension [NCT00195676]). Patients who were initially randomized to placebo and switched to continuous active treatment after Week 16 were selected as cohorts due to the comparability of study design and outcomes of interest. Patients with prior adalimumab were excluded from the deucravacitinib cohort. The primary outcome was PASI 75 at Week 112 since randomization and secondary outcomes were PASI 75 at Week 52 and PASI 90 at Weeks 52 and 112; missing PASI data was imputed using the last observation carried forward (LOCF) method. Matching-adjusted indirect comparison was conducted where individual patient-level data from POETYK PSO-LTE were reweighted to achieve balance with the summary baseline characteristics in the REVEAL extension trial: age, sex, race, weight, duration of psoriasis, body surface area affected, prior treatment history, baseline PASI and placebo PASI 75/90 responses at Week 16. Sensitivity analyses explored the effect of adjusting for prior treatment or not as well as history of psoriatic arthritis and patient's overall severity of disease.
 Results: Patients from POETYK PSO-LTE (N=329) were on average older, with lower weight, but with more prior systemic treatment exposure, higher baseline PASI score and higher placebo PASI 75/90 response at Week 16 than those in REVEAL (N=345). After adjustment, baseline differences between the two trials were mitigated. Results showed adjusted PASI 75 and PASI 90 response rate at Week 112 since randomization was higher for patients who were treated with deucravacitinib compared to those who were treated with adalimumab after 16 weeks of placebo: PASI 75= 67.2% vs 54% (mean difference [95% CI]= 13.2% [4, 22.5]); PASI 90= 41.3% vs 34% (7.3% [-2, 16.7]). Adjusted PASI 75 and PASI 90 at Week 52 were similar between the two cohorts. Results from the sensitivity analyses confirmed the base case findings.
 Conclusion: This indirect comparison analysis suggests that patients with moderate to severe plaque psoriasis with continuous active treatment on deucravacitinib had better long-term response than adalimumab and highlights the therapeutic role of deucravacitinib.

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

“…The first small molecule TYK2 inhibitor was approved by the FDA in 2022 for the treatment of psoriasis, with additional agents under investigation for use in other autoimmune conditions (57)(58)(59). TYK2 mediates signaling through several cytokines that have been linked with T1D pathogenesis, including IFNα, IL-12, and IL-23.…”