Risankizumab Shows Durable GRAPPA Improvements for PsA

Risankizumab provided durable improvement in the signs and symptoms of psoriatic arthritis (PsA) across all Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) disease domains and related conditions.1

“GRAPPA, founded in 2003, aims to develop and periodically update recommendations for the optimal treatment and management of patients with PsA, based on evolving scientific evidence. The most recent recommendations, updated in 2021, consider the advances in therapeutic options for PsA since GRAPPA’s previous recommendations in 2015. The updated GRAPPA recommendations consider the key domains of PsA which impact patients’ QoL and prognosis: peripheral arthritis, axial disease, enthesitis, dactylitis, skin and nail psoriasis, PsA-related conditions such as IBD and uveitis, and associated comorbidities,” study investigator Laura C. Coates, MBChB, PhD, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom, and colleagues wrote.1

Coates and colleagues conducted a post hoc analysis primarily using data from the phase 3 KEEPsAKE 1 trial of adult patients with PsA, with data from KEEPsAKE 2 pooled for prespecified outcomes. They looked at outcomes measuring risankizumab efficacy across key GRAPPA-recognized domains: peripheral arthritis, enthesitis, dactylitis, skin and nail psoriasis, axial disease, as well as and PsA-related conditions such as inflammatory bowel disease (IBD) and uveitis (evaluated via adverse events [AEs]) over 100 weeks of treatment (~2 years). They used mixed-effect models and imputed for non-responders for categorical variables.

The investigators analyzed data from 412/483 (85.3%) participants in KEEPsAKE 1 and 181/224 (80.8%) participants in KEEPsAKE 2 that completed treatment to week 100. They found that risankizumab demonstrated efficacy across all GRAPPA-defined domains through 100 weeks, including swollen and tender joint counts, enthesitis, dactylitis, skin and nail outcomes, and axial disease.

Notably, in KEEPsAKE 1, 12.2%, 23.4% and 25.9% achieved DAPSA remission, and 43.5%, 65.7% and 68.3% achieved DAPSA LDA/remission at week 24, 52 and 100, respectively. A Minimal Clinically Important Difference (MCID) in patient’s assessment of pain was achieved by 63.4%, 67.0% and 62.9% of patients receiving continuous risankizumab in KEEPsAKE 1 at week 24, 52 and 100, respectively. There was no structural progression observed at week 100 in 90.6% of patients in the cohort. Rates of new onset or flare of IBD and uveitis were low, with 4 four new onset cases reported with risankizumab for each (<0.1 E/100 PYs) and 4 flares for each (<0.1 E/100 PYs).

“Achieving comprehensive control across the multiple domains of PsA remains a challenge, with only one-third of treated patients with PsA achieving stringent disease control measures such as minimal disease activity or DAPSA LDA. The GRAPPA treatment recommendations take a comprehensive domain-based approach that ensures that both the primary PsA symptoms and the potential influence of comorbidities are taken into consideration when determining the most appropriate treatment strategy. It is noteworthy that not all patients will achieve optimal responses across all disease domains, and in these instances, it is important to examine the individual domains of PsA and implement a treat to target approach,” Coates and colleagues wrote.1

The investigators noted limitations of the analysis, including across both KEEPsAKE trials, including participants that exhibited high disease activity, which is typical of clinical trial populations but may restrict the generalizability of the results. For outcomes such as resolution of enthesitis, dactylitis, and axial disease, the number of patients with these baseline conditions was smaller than for other endpoints. In cases of psoriatic spondylitis or axial involvement, not all diagnoses were confirmed by imaging. Analyses of IBD- and uveitis-related outcomes were limited by the small number of participants with a history of these conditions, and comorbidities in PsA were not assessed in this study.

References

1. Coates LC, Blanco R, Behrens F, et al. Efficacy of risankizumab across GRAPPA domains in psoriatic arthritis: a pooled analysis of patients from the phase 3 KEEPsAKE 1 and 2 studies. RMD Open. 2025;11(3):e005522. Published 2025 Aug 25. doi:10.1136/rmdopen-2025-005522

2. Walsh JA, Ogdie A, Michaud K, et al. Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe. Joint Bone Spine. 2023;90(3):105534. doi:10.1016/j.jbspin.2023.105534