Guselkumab Linked With Long-term Improvement of Joint Manifestations, Disease Activity in PsA

Phase 3 findings of the DISCOVER-2 trial presented at the 2021 American College of Rheumatology Annual Meeting indicated that guselkumab (Tremfya) provided long-term improvement in joint manifestations, disease activity, and physical function among patients with psoriatic arthritis who had no prior biologic treatment.

Guselkumab (Tremfya) was associated with significant improvement long-term in joint manifestations, disease activity, and physical function among biologic-naive patients with psoriatic arthritis (PsA). Results were published in Arthritis & Rheumatology.

As a monoclonal antibody targeting the interleukin (IL)-23 p19 subunit, guselkumab is approved both for adults with moderate-to-severe psoriasis and active PsA ( (≥ 5 swollen and ≥ 5 tender joints; C-reactive protein [CRP] ≥ 0.6 mg/dL).

In prior findings investigating the therapy in biologic-naive patients with active PsA of the DISCOVER-2 trial, the IL-23 inhibitor was shown to provide greater improvements and higher response rates in several measures of joint and skin disease after 24 weeks, compared with placebo, which were maintained through 1 year. Lower radiographic progression after 24 weeks was also observed in study participants taking guselkumab.

Designed as a 2-year clinical trial, the final results of the analysis were presented at the 2021 American College of Rheumatology (ACR) Annual Meeting. A total of 739 biologic-naive patients with active PsA were randomized to receive guselkumab 100mg every 4 weeks (n = 245); at week 0, week 4, and week 8 (n = 248); or placebo (n = 246).

Effectiveness of the drug was determined by percentage improvements in disease activity measured via ACR criteria of greater than or equal to 20% (ACR 20), 50% (ACR 50), and 70% (ACR 70).

Further efficacy end points assessed were percentage of patients achieving Investigator’s Global Assessment of psoriasis score equal to 0 (IGA), indicating complete skin clearance, as well as enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score) resolution, and changes in PsA-modified van der Heijde-Sharp (vdH-S) radiographic scores.

“Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112,” added researchers.

Of the study participants randomized and treated, 652 (88%) completed treatment through week 100. Across groups of patients treated with placebo and guselkumab, 68% to 76% achieved ACR20, 48% to 56% achieved ACR50, and 30% to 36% achieved ACR70 at week 100, respectively.

In assessing the time to ACR20 response, separation from placebo was observed at week 4, and the proportion of patients experiencing 20% or more improvement in disease activity was maintained or continued to increase through week 100 for all ACR components.

Moreover, patients treated with placebo and guselkumab showed resolution rates of 55% to 67% regarding IGA, 62% to 70% for enthesitis, and 72% to 83% for dactylitis at week 100, respectively. Researchers said findings indicated durable amelioration of arthritis signs/symptoms and extra-articular manifestations.

Mean changes in PsA-modified vdH-S scores from week 52 to 100 (0.13-0.75) showed low rates of radiographic progression, and improvements in physical function and health-related quality of life seen at earlier timepoints of week 24 and 52 were also maintained at week 100.

Serious adverse events were reported in 8% and 3% of the week 4 and week 8 groups, respectively.

“Taken together, results from DISCOVER-2 demonstrate the robust and sustained efficacy of guselkumab in improving the signs and symptoms of PsA, including enthesitis and dactylitis, inhibiting radiographic progression, and decreasing the effects of PsA on physical function and HRQoL with a safety profile through 2 years that is consistent with the known safety profile of guselkumab,” they concluded.

Reference

McInnes IB, Rahman P, Gottlieb AB, et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through 2 years: results from a phase 3, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. Published online November 1, 2021. doi:10.1002/art.42010