Guselkumab Achieves Durable Control of Key Psoriatic Arthritis Endpoints

Christopher T. Ritchlin, MD, MPH

Credit: University of Rochester

The efficacy of guselkumab across stringent disease endpoints remained consistent among biologic-naive patients with highly active psoriatic arthritis (PsA) according to a post hoc analysis of the Phase 3 DISCOVER-2 trial.¹

Significant proportions of adults with active PsA, who received up to 2 years of guselkumab treatment, achieved sustained disease control across key domains and patient-reported outcomes (PROs), regardless of baseline characteristics, including disease activity and the concomitant use of conventional synthetic DMARDs (csDMARDs).

“The ability of guselkumab to provide durable disease control across key PsA domains and patient-reported outcomes (PROs), irrespective of baseline patient and clinical characteristics or concomitant csDMARD use, indicates it is an effective treatment option for diverse PsA patient types,” wrote the investigative team, led by Christopher T. Ritchlin, MD, MPH, University of Rochester Medical Center.

Recent treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) stress the importance of choosing treatments by disease activity that tackle the six key PsA domains: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.²

Across the Phase 3 DISCOVER-1 and DISCOVER-2 trials, guselkumab, a fully human monoclonal antibody targeting IL-23p19, achieved significantly greater efficacy in improving signs and symptoms of PsA versus placebo.^3,4 Posthoc analyses also revealed a consistent effect of guselkumab across PsA patient subgroups defined by baseline characteristics.⁵

DISCOVER-2 enrolled biologic-naive adults with active PsA and randomized the population 1:1 to receive guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at Week 0, Week 4, then Q8W, or placebo with crossover to guselkumab 100 mg Q4W at Week 24.¹ The current posthoc analysis assessed patterns of stringent disease control through 2 years, across key GRAPPA domains and PROs, in subgroups of patients defined by baseline characteristics.

The analysis evaluated the proportion of patients achieving the identified endpoints at Weeks 24, 52, and 100. At all time points, patients with missing categorical data were considered ‘non-responders.’ Among 739 patients randomized and treated in DISCOVER-2, 493 were randomized to guselkumab and 246 to placebo.

Of the guselkumab-treated patients, 442 (90%) completed treatment through Week 100 of the study. Ritchlin and colleagues identified a pattern of continuous improvement across key PsA domains and PROs within patient subgroups.

Skin response analyses revealed greater proportions of guselkumab-treated patients achieved 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100) and Investigator’s Global Assessment (IGA) 0 at Week 24, with sustained or increased response rates over time. At Week 100, most patients (50–70%) treated with guselkumab achieved complete skin clearance.

Moreover, among patients treated with guselkumab with baseline dactylitis or enthesitis, response rates for dactylitis or enthesitis resolution at Week 100 ranged from 65-85%, irrespective of baseline characteristics.

Ritchlin and colleagues also identified consistent response patterns for PROs. Across each baseline subgroup, most guselkumab-treated patients reported clinically meaningful improvement in activities of daily living at Week 100, with response rates from 60-70%.

Patients treated with guselkumab also experienced maintained or increased Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response rates from Week 52 through Week 100 in most baseline subgroups of adequate size, with significant proportions (60–75%) achieving response at Week 100.

Overall disease activity revealed greater proportions of guselkumab- versus placebo-treated patients achieved PsA Disease Activity Score (PASDAS) low disease activity (LDA). Rates of PASDAS LDA achievement increased through Week 100, regardless of baseline subgroup, with response rates ranging from 40-65%.

The investigative team also found a higher proportion of guselkumab-treated patients achieved minimal disease activity (MDA) at Week 24, with substantial increases in response rates through Week 100. Notable proportions (35–50%) of patients in the guselkumab cohort achieved MDA at Week 100.

“Thus, results of these analyses lend further support to guselkumab as an effective means of tailoring treatment to achieve low levels of disease activity across key domain involvement in individual patients,” investigators wrote.

References

1. _{Ritchlin CT, Mease PJ, Boehncke WH, et al. Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study. Clin Rheumatol. Published online June 7, 2024. doi:10.1007/s10067-024-06991-8}
2. _{Coates, L.C., Soriano, E.R., Corp, N. et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 18, 465–479 (2022). https://doi.org/10.1038/s41584-022-00798-0}
3. _{Deodhar A, Helliwell PS, Boehncke WH, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial [published correction appears in Lancet. 2020 Apr 4;395(10230):1114. doi: 10.1016/S0140-6736(20)30680-2]. Lancet. 2020;395(10230):1115-1125. doi:10.1016/S0140-6736(20)30265-8}
4. _{Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial [published correction appears in Lancet. 2020 Apr 4;395(10230):1114. doi: 10.1016/S0140-6736(20)30741-8]. Lancet. 2020;395(10230):1126-1136. doi:10.1016/S0140-6736(20)30263-4}
5. _{Ritchlin CT, Mease PJ, Boehncke WH, et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies. RMD Open. 2022;8(1):e002195. doi:10.1136/rmdopen-2022-002195}