Risankizumab Maintains PsA Disease Control Through 5 Years in KEEPsAKE 1 & 2 Trials

Risankizumab was shown to be a durable, well-tolerated option for psoriatic arthritis (PsA), maintaining musculoskeletal, dermatologic, and patient-reported improvements over ~5 years, according to data presented at the 2025 Fall Clinical Dermatology Conference.1

A post hoc analysis of the Phase 3 KEEPsAKE 1 and KEEPsAKE 2 trials assessed the durability of response to risankizumab, a humanized immunoglobulin G1 monoclonal antibody that inhibits interleukin-23 (IL-23) by targeting its p19 subunit, in patients with active psoriatic arthritis over 244 weeks (~5 years). IL-23 is considered to be a key driver of inflammatory autoimmune diseases.

The analysis included patients who achieved clinical response at week 24, evaluating whether efficacy was maintained long term across musculoskeletal, skin, pain, and axial domains.

Previous post hoc research analyzing the KEEPsAKE trials has demonstrated risankizumab provides lasting improvements in the signs and symptoms of PsA across all Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) disease domains (peripheral arthritis, enthesitis, dactylitis, skin and nail psoriasis, and axial disease), in addition to and PsA-related conditions such as inflammatory bowel disease (IBD) and uveitis over 100 weeks of treatment.2

Importantly, in KEEPsAKE 1, 12.2%, 23.4%, and 25.9% achieved Disease Activity in Psoriatic Arthritis (DAPSA) score remission, and 43.5%, 65.7% and 68.3% achieved DAPSA low disease activity (LDA)/remission at week 24, 52 and 100, respectively. Additionally, a Minimal Clinically Important Difference (MCID) in the patient’s assessment of pain was achieved by 63.4%, 67.0%, and 62.9% of patients treated with risankizumab in KEEPsAKE 1 at week 24, 52 and 100, respectively.2

Study Design

Patients in KEEPsAKE 1 had inadequate response or intolerance to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), and those in KEEPsAKE 2 had inadequate response or intolerance to 1–2 biologic disease-modifying antirheumatic drugs (bDMARDs) and/or ≥1 csDMARD.

• Intervention: Subcutaneous risankizumab 150 mg at weeks 0, 4, 16, and 24 (double-blind), then open-label risankizumab 150 mg every 12 weeks starting at week 28.
• Endpoints: Maintenance of American College of Rheumatology 20%, 50%, and 70% improvement (ACR20/50/70), Psoriasis Area and Severity Index (PASI) 90% improvement (PASI90), Minimal Disease Activity (MDA), patient pain outcomes, and axial symptom improvement through week 244.
• Analysis: Nonresponder imputation with multiple imputation for missing data (e.g., COVID-19 disruptions); as-observed analyses also reported.

Key Findings at a Glance

• Durable Long-Term Efficacy:
  Among risankizumab-treated patients with PsA who achieved a response at week 24, the majority maintained that response through week 244 across all endpoints.
• Joint and Skin Responses Maintained:
  Patients sustaining ACR20, ACR50, ACR70, and PASI90 responses at week 24 largely retained these through five years.
• Functional and Quality of Life Measures:
  • High proportions of patients maintained MDA (≥5 of 7 criteria met, including low pain, Health Assessment Questionnaire–Disability Index (HAQ-DI) ≤0.5, and minimal active joints/skin involvement).
  • Nearly half of patients sustained clinically meaningful pain reduction (≥10 mm decrease on visual analog scale [VAS]).
• Axial Involvement:
  Participants with baseline axial symptoms (mBASDAI >1.1) generally maintained clinically meaningful reductions (≥1.1 point improvement) through week 244.
• Discontinuation Rates:
  By week 244, 25.1% of KEEPsAKE 1 and 32.1% of KEEPsAKE 2 participants had discontinued—consistent with long-term studies of similar duration.

The IL-23 p19 inhibition mechanism—by stabilizing Th17 pathway control—appears to provide long-term disease suppression across multiple PsA domains.

References

1. Östör A., Amin A., Tillett W., et al. Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 5-Year Analysis of the KEEPsAKE 1 and 2 Trials. Poster presented at: 2025 Fall Clinical Dermatology. Las Vegas, NV. October 23-26, 2025.
2. Johnson V. RISANKIZUMAB shows durable grappa improvements for PSA: HCPLive. HCP Live. September 26, 2025. Accessed October 25, 2025. https://www.hcplive.com/view/risankizumab-durable-grappa-improvements-psa.