Date: Sunday, November 8, 2020
Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Guselkumab (GUS) is a human monoclonal antibody that specifically binds to the p19-subunit of IL-23. GUS has demonstrated efficacy across the various manifestations of PsA including skin, joint, soft tissue and structural damage at Week24 (W24) of DISCOVER-11 and DISCOVER-22, Phase 3 trials of patients (pts) with active PsA. Here we assess GUS efficacy through W24 in both studies utilizing composite indices.
Methods: Adult pts had active PsA despite standard therapies. DISCOVER-1 entry required ≥3 swollen & ≥3 tender joints and CRP ≥0.3 mg/dL; DISCOVER-2 required ≥5 swollen & ≥5 tender joints and CRP ≥0.6 mg/dL. 31% of DISCOVER-1 pts received 1-2 prior TNF inhibitors; DISCOVER-2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO). Composite endpoints included: Psoriasis Disease Activity Score (PASDAS), Minimal Disease Activity (MDA), Very Low Disease Activity (VLDA), Modified Psoriatic Arthritis Responder Criteria (mPsARC; based on evaluation of 68 joints for tenderness and 66 for swelling),3 Disease Activity Index for Psoriatic Arthritis (DAPSA), and clinical DAPSA (cDAPSA; determined by excluding CRP). Rates of achieving PASDAS Low/Very Low Disease Activity, MDA, VLDA, and DAPSA/cDAPSA Remission were pooled across studies (see Fig1-2 for response criteria). GUS vs PBO comparisons employed a Cochran-Mantel-Haenszel test with baseline stratification factors or Fisher’s exact test. Pts with missing data were imputed as nonresponders. P-values were not adjusted for multiplicity.
Results: In randomized and treated pts in DISCOVER-1 (N=381) and DISCOVER-2 (N=739), baseline characteristics were generally well-balanced across groups and reflected moderate-to-severe disease activity (Table). Across studies, differences between GUS Q4W or Q8W and PBO were observed as early as Week 8 and continued to increase over time when response was assessed using the joint-focused mPsARC or DAPSA Low Disease Activity (LDA)/Remission composite endpoints. Also in both studies, response rates determined by omitting CRP in calculating cDAPSA were similar to DAPSA results (Fig1). Higher proportions of GUS Q4W- and Q8W-treated than PBO-treated pts also achieved PASDAS (28% and 30% vs 9%), MDA (23% and 24% vs 8%, respectively), VLDA (6% and 4% vs 1%), and remission determined using either DAPSA (10% and 8% vs 2%) or cDAPSA (13% and 9% vs 3%; Fig2).
Conclusion: Regardless of composite index employed or study population assessed, GUS 100 mg Q4W and Q8W provided robust benefits to patients with active PsA across multiple domains, indicating that GUS may offer a novel mechanism by which to treat the diverse manifestations of PsA. Excluding CRP from the DAPSA did not alter the instrument’s ability to discern treatment effect.
- 1Deodhar A, et al. Lancet 2020;395:1115-25; 2Mease P, et al. Lancet 2020;395:1126-36; 3Mease PJ, et al. Arthritis Rheum 2005;52:3279–89.
To cite this abstract in AMA style:Coates L, Ritchlin C, Gossec L, Helliwell P, Rahman P, Hsia E, Kollmeier A, Xu X, Karyekar C, Shawi M, Noël W, Jiang Y, Sheng S, Agarwal P, Mease P. Guselkumab Provides Domain-Specific and Comprehensive Efficacy as Assessed Using Composite Endpoints in Patients with Active Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/guselkumab-provides-domain-specific-and-comprehensive-efficacy-as-assessed-using-composite-endpoints-in-patients-with-active-psoriatic-arthritis/. Accessed July 31, 2021.
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