Guselkumab Effective Treating Dactylitis and Enthesitis

Dennis McGonagle, PhD, FRCPI

A pair of clinical trials show positive results using guselkumab (GUS) to treat active psoriatic arthritis (PsA).

In data planned for presentation during the European Congress of Rheumatology (EULAR) 2020 meeting, a team, led by Dennis McGonagle, PhD, FRCPI, Leeds Biomed Res Ctr, University of Leeds, examined patients with dactylitis or enthesitis at baseline, while assessing changes in symptoms over time and relationships between improvements in dactylitis or enthesitis and other active psoriatic arthritis domains.

Guselkumab is a novel monoclonal antibody that specifically binds to the p19-subunity of IL-23. The treatment has already demonstrated efficacy in the Phase 3 DISCOVER-1 & DISCOVER-2 trials involving patients with active psoriatic arthritis.

Psoriatic arthritis comes with key clinical manifestations, including dactylitis and enthesitis, that are difficult to treat and could portend more significant disease burden.

The study included adults with active psoriatic arthritis despite standard therapies. In the first study, about 30% of patients previously received 1-2 TNF inhibitors, while the patients included in the second study were biologic-naïve.

Both the DISCOVER-1 and DISCOVER-2 trials were designed as randomized, double-blind, multicenter studies evaluating the safety of subcutaneously administered guselkumab in patients with active psoriatic arthritis. However, DISCOVER-1 was comprised of 381 patients who had previously been treated with a biologic anti-TNF agent and DISCOVER-2 consisted of 739 patients who were biologic-naive.

The patients were equally randomized to receive either guselkumab 100 mg every 4 weeks (Q4W) guselkumab 100 mg at baseline, week 4, and every 8 weeks after (Q8W), or placebo.

Independent assessors evaluated dactylitis (total score: 0-60) and enthesitis resolution by week 24. These scores were consistently significantly (P <0.001) associated with ACR20/50/70 and PASI75/90 response.

For the patients receiving guselkumab, there were significant correlations observed at week 24 between dactylitis change scores PASI (P <0.001 Q4W; P = 0.006 Q8W) and SF-36 MCS (P = 0.038 Q4W; P = 0.003 Q8W) changes, as well as between LEI and HAQ-DI change scores (P <0.001 Q4W; P = 0.005 Q8W).

There were no consistent correlations or associations observed between dactylitis or LEI scores and other clinical outcomes.

“In PsA [patients] with dactylitis or enthesitis at W0, GUS improved dactylitis or LEI scores vs PBO by W8; treatment differences were significant at W16 & W24,” the authors wrote. “Resolution of dactylitis or enthesitis was significantly associated with clinically meaningful improvements in PsA joint & skin symptoms. Improved dactylitis scores correlated with improved skin symptoms and mental health; improved LEI scores correlated with improved physical function.”

Previously, researchers presented at the 2019 American College of Rheumatology annual meeting, 24-week data highlighting guselkumab’s ability to achieve at least a 20% improvement in ACR 20 response compared to placebo in previously treated and biologic-naive patients.

Guselkumab has also proven superior in improved disease severity for patients with severe plaque psoriasis when compared to competitor secukinumab (Cosentyx), according to 2018 phase 3 trial results.

In data from the phase 3 ECLIPSE head-to-head study, a greater rate of patients administered guselkumab achieved an improvement of 90% or more Psoriasis Area Severity Index (PASI 90) score from baseline at week 48 than those administered secukinumab, an IL-17 inhibitor marketed by Novartis.

The study, “Effects Of Guselkumab, A Monoclonal Antibody That Specifically Binds To The P19-Subunit Of Interleukin-23, On Dactylitis And Enthesitis In Patients With Active Psoriatic Arthritis: Pooled Results Through Week 24 From Two Phase 3 Studies,” was published online by EULAR.