Risankizumab’s Durable Efficacy, Safety in PsA, With Frank Behrens, MD

Risankizumab 150 mg subcutaneously every 12 weeks demonstrated durable efficacy across joint, skin, and structural outcomes through 244 weeks — nearly 5 years — in patients with active psoriatic arthritis (PsA), according to long-term results from the KEEPsAKE 1 trial presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdom.¹

Study investigator Frank Behrens, MD, Professor of Translational Rheumatology, Immunology, and Inflammation Medicine, Head of the Inflammation Clinic at Goethe University Hospital Frankfurt, and Deputy Director of the Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt, Germany, sat down with RheumatologyLive during the meeting to further discuss the importance of the new data.

One-Third of Patients Achieve MDA at 244 Weeks

KEEPsAKE 1 (NCT03675308) was a global phase 3 trial enrolling 964 adults with moderately to severely active PsA who were csDMARD-inadequate responders and biologic-naïve. After a 24-week double-blind, placebo-controlled period, all patients received open-label risankizumab 150 mg every 12 weeks through the extension. Efficacy outcomes at week 244 and treatment-emergent adverse events (TEAEs) through data cutoff are reported.1

At week 244, 939 of 964 randomized patients (97.4%) had entered the extension period, and 714 remained actively enrolled at the data cutoff. ACR50 was achieved by 36.2% of patients receiving continuous risankizumab (RZB) and 38.0% of those who switched from placebo to risankizumab (PBO/RZB). Minimal disease activity (MDA) was achieved by 33.7% and 34.7%, respectively. Behrens noted that these response rates should be interpreted in the context of the analysis method used: as-observed analyses — which include only patients still in the trial, a positive selection of responders — show higher rates, while a modified non-responder imputation (mNRI) that excludes dropouts attributable to COVID-19 or geopolitical disruptions from the non-responder count yields MDA rates of 34–35%, which he described as "really outstanding data" for nearly 5 years of therapy.¹

Structural protection was notable. Among patients receiving continuous risankizumab, 88.4% showed no radiographic progression (PsA-modified Total Sharp Score change from baseline ≤0) at week 244, compared with 80.7% in the PBO/RZB group.1 Behrens emphasized the definition of a true DMARD as one that controls both signs and symptoms and inhibits structural damage and framed 88.4% non-progression at 244 weeks as confirming risankizumab's qualification on both counts. Additional outcomes at week 244 included PASI90 in 64.5% (RZB) and 59.9% (PBO/RZB) of patients with baseline BSA ≥3%; enthesitis resolution in 59.9% and 60.7%; and dactylitis resolution in 73.6% and 72.8%, respectively.¹

On long-term safety, TEAE rates (119.0 events/100 patient-years [E/100PY]), serious TEAEs (7.6 E/100PY), and TEAEs leading to discontinuation (1.8 E/100PY) remained stable through the extension period and were comparable to the double-blind phase.¹ Adjudicated MACE occurred in 13 patients (0.3 E/100PY) over the entire study period, with malignancy rates also lower than epidemiologically expected. Behrens referenced concurrent registry data presented at EULAR comparing MACE incidence across JAK inhibitors and biologics in PsA — noting that while no differences were observed in the first 2 years, an increased MACE risk beyond 2 years was observed for JAK inhibitors, while IL-23 and IL-17 inhibitors — including risankizumab — appeared to show a protective effect — a pattern consistent with the KEEPsAKE 1 long-term cardiovascular findings.¹

"All the safety discussion is already… finished, because we have a very promising and positive safety profile with the IL-23 inhibitors," Behrens said, adding that this becomes particularly relevant as the field moves toward dual targeted therapy combining JAK inhibitors or TNF inhibitors with IL-23 inhibition, where the safety of each component carries added importance.

Behren’s disclosures include AbbVie, Amgen, Affibody, Acelyrin, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Celltrion, Galapagos, Genzyme, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, Roche, Sandoz, and Sanofi.

References

1. Keiserman M, Papp K, White D, et al. Long-term efficacy and safety of risankizumab for csDMARD-IR patients with active psoriatic arthritis: 244-week results from the KEEPsAKE 1 trial. Presented at: EULAR 2026; June 3-6 in London, UK. Poster #POS0047

2. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Rheumatol Ther. 2024;11:617–632. doi:10.1007/s40744-024-00654-7