Guselkumab provides consistent long-term efficacy in psoriatic arthritis
Presenter: Iain McInnes, PhD, FRCP, University of Glasgow, Glasgow, United Kingdom
Consistent long-term guselkumab efficacy across psoriatic arthritis domains irrespective of baseline patient characteristics. Abstract 2128.
Guselkumab significantly improves the signs and symptoms of psoriatic arthritis across all baseline patient subgroups, including those with highly active disease, regardless of the dosing regimen for up to 2 years.
Patients with psoriatic arthritis may respond differently to treatment based on different baseline characteristics. In the phase 3 DISCOVER 1 and DISCOVER 2 studies, guselkumab significantly improved joint symptoms, skin disease, enthesitis, dactylitis, physical function, and quality of life at week 24 in patients with PsA. Clinical responses across these disease domains were maintained or increased with guselkumab at week 52, regardless of baseline patient demographics, disease characteristics, or conventional synthetic disease-modifying antirheumatic drug (DMARD) use. Durable efficacy with guselkumab through week 100 across multiple disease domains was observed.
“In this post-hoc analysis, we further evaluated the long-term efficacy of guselkumab from baseline to week 100 using DISCOVER 2 data by stratifying clinical improvements according to baseline patient characteristics and by assessing long-term predictors of guselkumab efficacy,” said presenter Iain McInnes, PhD, of the University of Glasgow, Glasgow, United Kingdom.
In the DISCOVER 2 study, biologic-naive patients with active PsA despite use of standard therapies were randomized to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. Guselkumab effects on joint, skin, enthesitis, dactylitis, spinal pain, and disease severity endpoints at week 100 were evaluated for guselkumab-randomized patients.
McInnes and colleagues developed a multivariate linear model adjusting for baseline patient characteristics to assess associations between baseline predictors and changes in Disease Activity in PsA (DAPSA), Psoriasis Area Severity Index (PASI), and Leeds Enthesitis Index (LEI) scores from baseline to week 100.
“Patients enrolled in DISCOVER 2 had active PsA based on swollen and tender joints and systemic inflammation regardless of treatment group. Patients randomized to guselkumab for 4 or 8 weeks had similar characteristics at baseline,” McInnes said.
A total of 442 patients randomized to guselkumab completed treatment through week 100. The new analysis found PsA duration, swollen joint count, and tender joint count were significant predictors of long-term DAPSA score change. The percent of body surface area, PASI score, swollen joint count, and conventional synthetic DMARD use were significant predictors of long-term PASI score change. No baseline characteristics significantly predicted long-term improvement in spinal pain or LEI score.
“Guselkumab improved DAPSA, PASI, and LEI scores from baseline to week 100,” he said.
In conclusion, McInnes said, “Significant long-term improvements among pooled guselkumab patients were seen across clinical domains. Improvements were observed regardless of patient characteristics, including baseline demographics, disease features, and DMARD use.”
References
Deodhar A, Helliwell PS, Boehncke WH, et al, DISCOVER-1Study Group. 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. Lancet 2020; 395(10230):1115-1125. doi:10.1016/S0140-6736(20)30265-8
McInnes IB, Rahman P, Gottlieb AB, et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through two years: results from a phase III, randomized, double-blind, placebo-controlled study conducted in biologic-naive patients with active psoriatic arthritis. Arthritis Rheumatol 2021; 74(3):475-485. doi:10.1002/art.42010
McInnes IB, Rahman P, Gottlieb AB, et al. Efficacy and safety of guselkumab, an interleukin-23 p19-specific monoclonal antibody, through one year in biologic-naive patients with psoriatic arthritis. Arthritis Rheumatol 2021; 73(4):604-616. doi:10.1002/art.4155
McInnes I, Tesser J, Schiopu E, et al. Consistent long-term guselkumab efficacy across psoriatic arthritis domains irrespective of baseline patient characteristics [abstract 2128]. Arthritis Rheumatol 2022; 74(suppl 9). https://acrabstracts.org/abstract/consistent-long-term-guselkumab-efficacy-across-psoriatic-arthritis-domains-irrespective-of-baseline-patient-characteristics/
Mease PJ, Rahman P, Gottlieb AB, et al, DISCOVER-2 Study Group. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020; 395(10230):1126-1136. doi:10.1016/S0140-6736(20)30263-4
Ritchlin CT, Helliwell PS, Boehncke W-H, et al. Guselkumab, an inhibitor of the IL- 23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naive or TNFα inhibitor-experienced. RMD Open 2021; 7(1):e001457. doi:10.1136/rmdopen-2020-0014574
Ritchlin CT, Mease PJ, Boehncke WH, et al. AB0526 Sustained guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase 3, randomized, placebo-controlled studies. Ann Rheum Dis 2021; 80:1291-1292. doi:10.1136/annrheumdis-2021-eular.43
Disclosures
Iain McInnes: Bristol Myers Squibb, Janssen Pharmaceuticals, Novartis, UCB, Pfizer, AbbVie, Celgene, AstraZeneca, Boehringer Ingelheim, Evelo Biosciences, Leo Pharma, Eli Lilly and Company.