Patients with psoriatic arthritis (PsA) who underwent guselkumab therapy demonstrated robust and consistent low disease activity across skin and joint domains through 1 year, according to study results published in Rheumatology.
The safety and efficacy of guselkumab in patients with active PsA were assessed in the DISCOVER-1 (ClinicalTrials.gov Identifier: NCT03162796) and DISCOVER-2 (ClinicalTrials.gov Identifier: NCT03158285) phase 3 studies. This study pooled data from these trials to assess guselkumab efficacy using multiple composite PsA disease activity indices.
In both DISCOVER-1 (n=381) and DISCOVER-2 (n=739), patients were randomly assigned in a 1:1:1 ratio to receive either 100 mg subcutaneous guselkumab every 4 weeks (Q4W), 100 mg guselkumab at weeks 0 and 4 then every 8 weeks (Q8W), or placebo with crossover at week 24 to 100 mg guselkumab Q4W. Efficacy was determined as the proportion of patients who achieved Disease Activity Index for Psoriatic Arthritis (DAPSA) low disease activity (LDA), DAPSA remission, Psoriatic Arthritis Disease Activity Score (PASDAS) LDA, PASDAS very LDA (VLDA), minimal disease activity (MDA), and VLDA. Through week 24, data was imputed as nonresponse for patients meeting treatment failure criteria and missing data. After week 24, nonresponder imputation was used for missing data but treatment failure rules were not applied.
At week 24, patients in the guselkumab treatment group experienced higher response rates for all the composite indices (DAPSA LDA, DAPSA remission, PASDAS LDA, PASDAS VLDA, MDA, and VLDA) compared with the placebo group (unadjusted P <.05), with treatment effects observed by week 8 for most of the indices.
Response rates in the guselkumab treatment groups increased from weeks 24 to 52, with no plateau observed for PASDAS LDA, PASDAS VLDA, MDA, or VLDA, which suggested a potential for higher response rates beyond 52 weeks. Results among the Q4W and Q8W groups, respectively, are shown:
- DAPSA LDA (54.2% and 52.5%)
- DAPSA remission (18.2% and 17.6%)
- PASDAS LDA (45.3% and 41.9%)
- PASDAS VLDA (16.9% and 19.5%)
- MDA (35.9% and 30.7%)
- VLDA (13.1% and 14.4%)
In the placebo group, response rates for all the composite indices increased from week 24 to week 52, after patients switched to guselkumab.
Limitations of the study included the rigid enrollment criteria for the DISCOVER-1 and DISCOVER-2 studies, and the post-hoc nature of the analysis, which may have restricted generalizing the results to all patients.
The study authors concluded, “Taken together, results of these analyses indicate that patients with active PsA who receive treatment with guselkumab Q4W or Q8W can achieve robust and sustained low disease activity or remission, based on various composite indices that measure responses across domains including joint pain, swelling, stiffness, inflammation, and tenderness; and skin clearance. As such, guselkumab is a novel therapy for PsA that can provide effective treatment of the diverse manifestations of this disease.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Coates LC, Ritchlin CT, Gossec L, et al. Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis. Rheumatology (Oxford). Published online June 29, 2022. doi:10.1093/rheumatology/keac375