Guselkumab improves psoriatic arthritis disease activity in multiple composite scores
Presenter: Laure Gossec, MD, PhD, Sorbonne Universite, Paris, France
Guselkumab efficacy in psoriatic arthritis assessed by multi-domain composite indices: Data from the phase 3b COSMOS trial in a TNFi-IR population.
Guselkumab provides substantial improvement in disease activity across multiple composite scores for patients with active psoriatic arthritis (PsA) who were refractory to tumor necrosis factor (TNF) inhibitor therapy.
A handful of composite measures of disease activity have been developed for patients with psoriatic arthritis (PsA), some that are joint focused and others that are multidimensional. “We used data from the phase 3b COSMOS study to compare composite scores for patients treated with guselkumab versus placebo,” said presenter Laure Gossec, MD, PhD, Sorbonne Universite, Paris, France.
The COSMOS study demonstrated the efficacy and safety of guselkumab, an IL-23 p19 subunit inhibitor, in patients with PsA who had inadequate response to 1 or 2 TNF inhibitors. A total of 285 patients (189 guselkumab, 96 placebo) were enrolled; their mean age was 49 years and they had a mean disease duration of 8.4 years. Patients who received placebo crossed over to guselkumab at either week 16 or week 24.
The purpose of the new analysis was to assess the efficacy of guselkumab (100 mg every 8 weeks) through 1 year by using and comparing 6 multi-domain composite indexes validated for PsA: PsA Disease Activity Score (PASDAS), GRAppa Composite scorE (GRACE), Disease Activity Index for PsA (DAPSA), modified Composite Psoriatic Disease Activity Index (mCPDAI, excludes BASDAI), PsA Response Criteria (PsARC), and Minimal Disease Activity (MDA).
Nearly 90% of patients in the arms completed the study through week 44. Patients had active disease, with similar baseline mean values for PASDAS, GRACE, DAPSA, and mCPDAI in the two groups.
“The composite scores at the 1 year follow-up showed a clear improvement in guselkumab-treated patients, with improvements of 45% to 62% in mean scores from baseline to week 48,” said Gossec. “Placebo recipients who crossed over to guselkumab also showed clear improvement in their index scores, with mean values and percentage improvement at week 48 of similar magnitude with those observed in patients randomized to guselkumab at baseline.”
Over 1 year, patients reached a high rate of low disease activity, she said. Of the 4 indexes with defined disease states or therapeutic thresholds for low disease activity, those focusing on joints (PsARC [4 components] and DAPSA [5 components]) resulted in the highest response rates, with a range of 50% to 80%. Low disease activity according to GRACE (8 items, including skin) and PASDAS (8 items, focus on musculoskeletal with no skin assessment) was attained less frequently, with a range of 38% to 44%. Using the PsARC, 50% of guselkumab patients responded as early as week 8.
Response rates among guselkumab-treated patients generally did not plateau by week 48. At that time, one-third of guselkumab-treated patient and 30% of placebo-treated patients achieved minimal disease activity.
In conclusion, Gossec said, “Guselkumab provided robust and substantial benefits in improvements in patients with active PsA who were refractory to TNF inhibitor therapy across multiple composite scores. Importantly, rates of achieving low levels of disease activity continued to increase through the duration of the study without an observable plateau at week 48. Response thresholds for joint-focused indexes such as DAPSA and PsARC were easier to achieve than comprehensive indices with more domains, which shows the difficulty in reaching substantial improvement in all domains of PsA.”
“Guselkumab performed well regardless of the focus of the composite indices (joints, skin, enthesitis, dactylitis, or patient-reported outcomes),” she added. “Together, these findings support the role of guselkumab as an effective treatment option for the diverse domains of PsA.”
References
Coates LC, Gossec L, Theander E, et al. Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS). Ann Rheum Dis 2022; 81(3):351—369. doi:10.1136/annrheumdis-2021-220991
Helliwell PS, Deodhar A, Gottlieb AB, et al. Composite measures of disease activity in psoriatic arthritis: comparative instrument performance based on the efficacy of guselkumab in an interventional phase II trial. Arthritis Care Res (Hoboken) 2020; 72(11):1579—1588. doi:10.1002/acr.24046
Clunie G, McInnes IB, Barkham N, et al. Long-term effectiveness of tumour necrosis factor-α inhibitor treatment for psoriatic arthritis in the UK: a multicentre retrospective study. Rheumatol Adv Pract 2018; 2(2):rky042. doi:10.1093/rap/rky042
Gossec L, Sharaf M, Theander E, et al. Guselkumab efficacy in psoriatic arthritis assessed by multi-domain composite indices: data from the phase 3b COSMOS trial in a TNFi-IR population [abstract 2110]. Arthritis Rheumatol 2022; 74 (suppl 9). https://acrabstracts.org/abstract/guselkumab-efficacy-in-psoriatic-arthritis-assessed-by-multi-domain-composite-indices-data-from-the-phase-3b-cosmos-trial-in-a-tnfi-ir-population/
Disclosures
Laure Gossec: Amgen, Eli Lilly, Pfizer, Sandoz, UCB Pharma, AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Novartis, Samsung Bioepis, Sanofi-Aventis, Galapagos, GSK, Celltrion, MSD