Janssen Announces Two-Year Efficacy and Safety Data for TREMFYA® (guselkumab) in Active Psoriatic Arthritis from Phase 3 DISCOVER-2a Study

Compiled by Keke

On March 16, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced long-term data from the Phase 3 DISCOVER-2a study. The trial confirmed the sustained efficacy of TREMFYA® (guselkumab) in achieving skin clearance, alleviating joint symptoms, and maintaining safety over two years (Week 112) following 24 weeks and one year (52 weeks) of treatment in patients with active psoriatic arthritis (PsA). Furthermore, the study demonstrated robust efficacy in patients who received 24 weeks of TREMFYA therapy and continued treatment through Week 100, showing improvements in physical function, the physical component of health-related quality of life, resolution of enthesitis (inflammation at the sites where tendons and ligaments attach to bone), and reduction of dactylitis (inflammation of the fingers and toes). Additionally, the trial assessed radiographic progression over the two-year period.

DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating the efficacy and safety of TREMFYA subcutaneous injection in patients with active psoriatic arthritis (PsA), including those who had previously been treated with one or two biologic tumor necrosis factor (TNF) inhibitors. The DISCOVER-2 study evaluated 739 patients over a period of approximately two years.

The study included a screening period of up to 6 weeks, a blinded active-treatment period (approximately 100 weeks) comprising a placebo-controlled phase from Week 0 to Week 24 and an active-treatment phase from Week 24 to Week 100, as well as a safety follow-up period of 12 weeks after the last dose of the study drug.

The DISCOVER-2a study results showed that at Week 100:

—Complete Skin Clearance: Among patients with clinically significant skin involvement at baseline, 59% of those receiving TREMFYA every 4 weeks (q4w) and 53% of those receiving TREMFYA every 8 weeks (q8w) achieved complete skin clearance (Psoriasis Area and Severity Index [PASI] 100; using non-responder imputation [NRI], where subjects with missing data are assumed to be non-responders in this analysis method).

— Improvement in Joint Symptoms: Among randomized patients, 76% of those treated with TREMFYA q4w and 74% of those treated with TREMFYA q8w met the American College of Rheumatology (ACR20) response criteria, achieving at least a 20% improvement in skin symptoms.

— Radiographic Progression: At Week 24, patients in the TREMFYA q4w group demonstrated a statistically significant inhibition of radiographic progression of joint structural damage (p=0.011) (as measured by the PsA-modified van der Heijde Sharp [vdH-S] score). However, the results for the TREMFYA q8w group were not statistically significant, although less radiographic progression was observed compared with placebo (p=0.072). From Weeks 52 to 100, lower rates of radiographic progression of joint damage were observed in patients treated with TREMFYA q4w (0.75) and TREMFYA q8w (0.46), with both treatments showing further numerical reductions compared with the results observed during Weeks 0–52 (1.06 for q4w; 0.99 for q8w). In patients who switched from placebo to TREMFYA q4w at Week 24, the mean change in vdH-S score was 1.12 during Weeks 0–24 (while on placebo); in patients treated with TREMFYA q4w, the mean change in vdH-S score was 0.34 during Weeks 24–52 and 0.13 during Weeks 52–100, indicating further numerical improvement in this group during the second year.

—Durability: Within two years, the rates of effective response in joints and skin and the mean improvement rates remained at baseline levels; approximately 90% of patients randomized to receive TREMFYA every 4 weeks (q4w) or every 8 weeks (q8w) continued TREMFYA treatment through 100 weeks.

— Safety: No new safety signals were observed in the safety analysis at Week 112. The safety profile of TREMFYA over two years in patients with active psoriatic arthritis (PsA) was consistent with that observed at 6 months and 1 year, and was largely aligned with the safety profile of TREMFYA in patients with moderate-to-severe plaque psoriasis (PsO).

Furthermore, trial results showed that 56% of patients treated with TREMFYA q4w and 55% of patients treated with TREMFYA q8w achieved at least a 50% improvement in ACR score. Among patients with clinically significant psoriasis (PsO) at baseline, 62% of those treated with TREMFYA q4w and 55% of those treated with TREMFYA q8w achieved complete skin clearance, with an Investigator’s Global Assessment (IGA) score of 0.

TREMFYA is the first and only treatment approved for adult patients with moderate-to-severe plaque psoriasis (PsO) and active psoriatic arthritis (PsA) that selectively inhibits interleukin-23 (IL-23), a cytokine that is a key driver of the inflammatory immune response associated with the symptoms of these chronic autoimmune diseases. The drug was first approved in the United States in July 2017 for the treatment of adults with moderate-to-severe plaque PsO, and subsequently approved in July 2020 for the treatment of adults with active PsA. The approval for the PsA indication was based on the results of DISCOVER-1 and DISCOVER-2, which demonstrated that TREMFYA met the primary endpoint of each study, achieving an ACR 20 response at 24 weeks.

Reference Sources:

1.New Phase 3 Data Show First-in-Class TREMFYA® (guselkumab) Achieved Complete Skin Clearance and Favorable Joint Efficacy in Adult Patients with Active Psoriatic Arthritis (PsA) Through Two Years

2.Janssen's Psoriatic Arthritis Drug Proves Long-Term Efficacy in Two-Year Trial