Johnson & Johnson announced a new post-hoc analysis of the Phase 3 DISCOVER program (DISCOVER-1 and DISCOVER-2) evaluating TREMFYA® (guselkumab) in adult patients with active psoriatic arthritis (PsA), which showed that early skin and enthesitis responsesa,b predicted longer-term clinical response,c including disease remission, at week 52.1 TREMFYA is the first fully human selective interleukin (IL)-23 inhibitor therapy approved in the U.S. for adults with moderate to severe plaque psoriasis (PsO) and adults with active PsA. In another post-hoc analysis of DISCOVER-2, a diverse population of bio-naïve, TREMFYA-treated patients sustained several PsA disease control endpoints through two years, regardless of their baseline characteristicsd or dosing regimen,e including minimal disease activity (MDA) response,f skin clearance (IGA 0)g and resolution of dactylitis. At week 24, early skin responsea was associated with greater odds of achieving MDA, Disease Activity in Psoriatic Arthritis (DAPSA) Low Disease Activity (LDA), DAPSA remission, and DAPSA50k in PsA.

Early entheseal response was associated with greater odds of achieving MDA, DAPSA LDA, DAPSA50, and resolution of enthesitis or dactylitis. DAPSA remission was achieved by a greater proportion of early entheseal responders, though the association was significant only at week 52. Among patients with baseline PsO and enthesitis, a dual effect was observed: those who responded early in both domains were more likely to achieve clinical response (MDA, DAPSA LDA, DAPSA50, DAPSA remission) than patients with individual responses to these domains.

These results highlight the importance of early entheseal and skin responses on the trajectory of future patient outcomes. Sustained achievement of stringent endpoints spanning key GRAPPA-recommended domains, including ACR50 and ACR70, IGA 0, dactylitish and enthesitis resolution, and MDA responses was seen across a variety of diverse, baseline demographicsd (sex, body mass index [BMI]) and disease characteristics (swollen joint count [SJC], tender joint count [TJC], PsA duration, C-reactive protein [CRP], Body Surface Area [BSA], Psoriasis Area and Severity Index [PASI]). At week 100, sustained achievement of stringent endpoints was observed across all domains (MDA response, IGA 0 and resolution of dactylitis), irrespective of use of concomitant therapies (nbDMARDs and methotrexate [MTX]) No consistent differences were observed in the proportion of responders across patient subgroupsd of adequate sample size or between TREMFYA dosing regimens.

Results of this post-hoc analysis further support the long-term efficacy (week 100) of TREMFYA across the full spectrum of active PsA disease domains and diverse PsA populations. DISCOVER-1 was a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by SC injection in participants with active PsA, including those previously treated with one or two TNF inhibitors. DISCOVER-1 evaluated 381 participants who were treated and followed through approximately one year.

The study consisted of a screening phase of up to six weeks, a blinded treatment phase of 52 weeks that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period from week 24 to week 52. It also included a safety follow-up phase through week 60 (i.e., approximately 12 weeks from the last administration of study agent at week 48). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations were performed in the study on a defined schedule.

DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by SC injection in biologic-naïve patients with active PsA. DISCOVER-2 evaluated 739 participants who were treated and followed through approximately two years. The study consisted of a screening phase of up to six weeks, a blinded treatment phase of approximately 100 weeks that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period from week 24 to week 100.

It also included a safety follow-up phase through week 112 (i.e., approximately 12 weeks after the last administration of study agent at week 100). Clinical efficacy, radiographic efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker, and pharmacogenomics evaluations were performed in the study on a defined schedule. PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis (pain where the bone, tendon and ligament meet), dactylitis (a type of inflammation in the fingers and toes that can result in a swollen, sausage-like appearance), axial disease, and the skin lesions associated with plaque PsO.4,6,14 The disease causes pain, stiffness and swelling in and around the joints; it commonly appears between the ages of 30 and 50, but can develop at any age15.

Nearly half of patients with PsA experience moderate fatigue and about 30% suffer from severe fatigue as measured by the modified fatigue severity scale.15 In patients with PsA, comorbidities such as obesity, cardiovascular diseases, anxiety and depression are often present.16 Studies show up to 30% of people with plaque PsO also develop PsA.17 Although the exact cause of PsA is unknown, genes, the immune system and environmental factors are all believed to play a role in disease onset. Developed by Janssen, TREMFYA is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is an important driver of the pathogenesis of inflammatory diseases such as moderate to severe plaque PsO and active PsA.

TREMFYA is approved in the U.S., Canada, Japan, and a number of other countries worldwide for the treatment of adults with moderate to severe plaque PsO who are candidates for injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light), and for the treatment of adult patients with active PsA. It is also approved in the EU for the treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy and for the treatment of active PsA in adult patients who have had an inadequate response or who have been intolerant to a prior csDMARD therapy.