Guselkumab Treatment Linked to Dactylitis Resolution in Patients With Psoriatic Arthritis

Most patients (approximately 75%) with psoriatic arthritis (PsA) and dactylitis treated with guselkumab through week 52 reported complete resolution of dactylitis and were more likely to achieve other clinical outcomes, according to a study published ACR Open Rheumatology.¹

Dennis McGonagle FRCPI, PhD

Image Credit: Medicom

Dactylitis, which presents as swelling of the digit and inflammation in soft tissues, tendon sheaths, and joints, develops in approximately half of patients with PsA during their disease course.²

“In patients with chronic PsA, dactylitis is associated with a higher degree of radiographic damage,” Dennis McGonagle FRCPI, PhD, associated with the Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM) at the University of Leeds, and a team of investigators, explained. “Development of dactylitis is a predictor of future radiographic damage, and patients with PsA with dactylitis and/or enthesitis report higher levels of physical disability, poorer functional status, and greater pain and fatigue than patients without these disease features. Furthermore, resolution of dactylitis is associated with improvements in physical function, health-related quality of life, and pain.”

The multicenter, randomized, double-blind, placebo-controlled, phase 3 DISCOVER-1 (NCT03162796) and DISCOVER-2 (NCT03158285) studies were used to evaluate dactylitis resolution, among other outcomes, through 1 year. Patients were randomized to receive subcutaneous guselkumab 100 mg at week 0, 4, and then every 4 (Q4W) or 8 (Q8W) weeks, or placebo with a crossover to guselkumab at week 24 (placebo→Q4W).

The dactylitis severity score (DSS) was analyzed by independent assessors. Resolution, defined as a DSS score of 0, and at least 20%, 50%, and 70% DSS improvement from baseline were evaluated through 1 year. Other outcomes of interest included tender and swollen joints, low disease activity (LDA), and the American College of Rheumatology 50% improvement criteria (ACR50) in patients with dactylitis versus without dactylitis resolution at both week 24 and week 52.

Demographics and disease characteristics were similar across treatment groups in both studies. Among patients with dactylitis, 41% experienced both finger and toe dactylitis, 35% had toe dactylitis, and 24% had finger dactylitis.

Those with dactylitis at baseline (n = 473/1118, 42%), including 42% of patients in the placebo group (n = 154/371), were more likely to experience more severe joint and skin disease when compared with patients without dactylitis (n = 645/1118).

At 1 year, approximately 75% of patients with dactylitis treated with guselkumab were able to achieve complete resolution and roughly 80% had at least 70% DSS improvement. Further, patients with dactylitis resolution receiving guselkumab treatment were more likely to achieve ACR50, LDA, and experience a 50% reduction in tender and swollen joints at week 24 and week 52 compared with those who were unable to achieve resolution. According to results from the DISCOVER-2 study, patients who obtained dactylitis resolution had less radiographic progression.

Dactylitis assessment is subjective, and assessors may have overestimated the prevalence of dactylitis when compared with real-world settings. This may have attributed to the high placebo response in the DISCOVER studies. Further, 64% of patients with and without dactylitis reported using nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline which may have helped to reduce pain and swelling in dactylitic joints which may have impacted the DSS measurements. The short study time frame was noted as another limitation, although dactylitis resolution rates were maintained through week 100 in DISCOVER-2.

“Guselkumab treatment is effective in resolving dactylitis in a broad range of patients with PsA, highlighting the role of interleukin-23 (IL-23) inhibition in controlling this important disease domain and emphasizing the importance of IL-23 in PsA pathophysiology and therapy,” investigators concluded.

References

1. ^{McGonagle D, McInnes IB, Deodhar A, et al. Guselkumab, a Selective Interleukin-23 p19 Subunit Inhibitor, Resolves Dactylitis in Patients With Active Psoriatic Arthritis: Pooled Results Through Week 52 From Two Phase 3 Studies [published online ahead of print, 2023 Mar 7]. ACR Open Rheumatol. 2023;10.1002/acr2.11537. doi:10.1002/acr2.11537}
2. ^{Dubash S, Alabas OA, Michelena X, et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis 2022;81:490–5.}