Guselkumab enhances responses in patients with psoriatic arthritis and active axial involvement
Presenter: Philip Mease, MD, Swedish Medical Center/Providence-St Joseph Health, Seattle, WA
Efficacy of guselkumab in three cohorts of biologic-naive PsA patients with axial involvement defined based on imaging and machine-learning criteria: Pooled analysis of two phase 3 studies. Abstract 1035. Presented November 13, 2022.
Patients with psoriatic arthritis and active axial involvement treated with guselkumab show significant and clinically meaningful improvements in disease activity after 2 years.
Evidence on the efficacy of advanced therapies for axial involvement in psoriatic arthritis (PsA) is scarce, largely due to the lack of a widely accepted definition. Guselkumab, an IL-23p19 inhibitor, demonstrated early and sustained improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) among patients from the DISCOVER-1 and DISCOVER-2 studies, with imaging-confirmed sacroiliitis consistent with axial involvement.
In the DISCOVER studies, a cluster of patients with axial involvement had been identified. “We sought to contrast patient profiles across axial involvement in PsA cohorts defined by imaging and machine learning criteria and to evaluate the efficacy of guselkumab in improving disease activity across the cohorts,” according to the presenter, Philip Mease, MD, Swedish Medical Center/Providence-St Joseph Health, Seattle, WA.
Patients enrolled in DISCOVER-1 and DISCOVER-2, adults with active PsA despite standard therapies, had been randomized to guselkumab at 100 mg every 4 weeks; guselkumab at week 0, week 4, then every 8 weeks; or placebo. The current post-hoc analysis included only bio-naive guselkumab-treated patients who met 1 of the following definitions of axial involvement in PsA: presence of spondylitis based on imaging confirmation; machine learning-identified axial cluster; or both imaging and machine learning definitions.
A total of 185 patients met the axial involvement criteria: 81 patients met the imaging criteria, 81 patients were identified by machine learning, and 77 met both definitions. Approximately 95% in the machine learning cohort also met imaging criteria. Baseline characteristics were generally comparable, Mease said. Some numerical differences in baseline characteristics were observed, suggesting less active peripheral disease in the machine learning cohort.
“Irrespective of axial involvement in PsA definition, guselkumab treatment was associated with significant decreases in BASDAI, mBASDAI, BASDAI Q2 (spinal pain), BASDAI Q5/6 (morning stiffness), and ASDAS scores at week 8, with continued improvement through week 24,” Mease said.
Consistent response patterns were observed across axial involvement in PsA cohorts, with substantial proportions of guselkumab-treated patients achieving clinically important improvements as early as week 8. The BASDAI and ASDAS response rates increased over time, regardless of assessment tool and rigor of endpoint.
In conclusion, Mease said: “Irrespective of the definition used to identify axial involvement in PsA patients in the DISCOVER-1 and DISCOVER-2 studies, that is, imaging-confirmed sacroiliitis consistent with axial involvement versus unsupervised machine learning cluster, patients with active axial involvement in PsA treated with guselkumab had significant and clinically meaningful improvements in BASDAI, modified BASDAI, and ASDAS responses as early as week 8 and continued through week 24. These results further support the efficacy of guselkumab in treating PsA patients with axial involvement.”
References
Mease PJ, Helliwell PS, Gladman DD, et al. Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studies. Lancet Rheumatol 2021; 3(10):e715-e723. https://doi.org/10.1016/S2665-9913(21)00105-3
Mease PJ, Tillett W, Ohrndorf S, et al. Efficacy of guselkumab in three cohorts of biologic-naïve PsA patients with axial involvement defined based on imaging and machine-learning criteria: pooled analysis of two phase 3 studies [abstract 1035]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/efficacy-of-guselkumab-in-three-cohorts-of-biologic-naive-psa-patients-with-axial-involvement-defined-based-on-imaging-and-machine-learning-criteria-pooled-analysis-of-two-phase-3-studies/
Richette P, Vis M, Ohrndorf S, et al. Identification of PsA phenotypes with machine learning analytics using data from a phase 3 clinical trial program of guselkumab in a bio-naïve population of patients with PsA [abstract 1363]. Arthritis Rheumatol 2021; 73(suppl 9). https://acrabstracts.org/abstract/identification-of-psa-phenotypes-with-machine-learning-analytics-using-data-from-a-phase-3-clinical-trial-program-of-guselkumab-in-a-bio-naive-population-of-patients-with-psa
Disclosures
Philip Mease, MD: AbbVie, Amgen, Janssen, Novartis, Pfizer, UCB, Sun Pharma, Eli Lilly and Co, Bristol Myers Squibb, Celgene, Genentech.