Main Article Content
Clinical trials, Moderate-to-Severe Psoriasis, risankizumab, PASI 90, PASI 100
Introduction: Interleukin (IL)-23 is a key regulator of plaque psoriasis pathogenesis. Risankizumab, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits IL-23 by binding to its p19 subunit, is approved for the treatment of moderate-to-severe plaque psoriasis in adults; however, additional data on long-term maintenance of efficacy with risankizumab treatment are needed. Here we report on the maintenance of clinical response through 304 weeks of continuous risankizumab treatment.
Methods: In this interim analysis, we evaluated patients with moderate-to-severe plaque psoriasis who were randomized to receive risankizumab 150 mg at weeks 0, 4, and 16 and every 12 weeks thereafter during 2 double‑blind, phase 3, 52-week base studies (UltIMMa 1 [NCT02684370] and UltIMMa 2 [NCT02684357]) and enrolled in LIMMitless, an ongoing, phase 3, multicenter, single‑arm, open-label extension (OLE) study (NCT03047395) evaluating the long-term safety and efficacy of continuous risankizumab 150 mg treatment every 12 weeks for plaque psoriasis. Safety was assessed through ≤ 324 weeks by monitoring of treatment‑emergent adverse events through the data cutoff date (May 22, 2023). Efficacy was assessed by the proportion of patients who maintained ≥ 90% or 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 90/100) during LIMMitless and mean improvement in PASI from baseline of the UltIMMa-1/2 study through 252 additional weeks in the LIMMitless study (total of 304 weeks). Missing efficacy data were imputed using modified nonresponder imputation (mNRI), last observation carried forward (LOCF), or observed cases (OC) methodology.
Results: A total of 525 patients were randomized to receive risankizumab 150 mg treatment for 52 weeks in the UltlMMa‑1/2 studies and continued open-label risankizumab 150 mg treatment in the LIMMitless OLE study. Risankizumab was well tolerated through ≤ 324 weeks; no new safety concerns were reported in patients with moderate-to-severe plaque psoriasis. At OLE entry, most patients (451, 85.9%) achieved PASI 90; of those, 422 (93.6%) maintained PASI 90 through week 304 by mNRI (LOCF, 92.7%; OC, 93.8%). Of 320 patients (61.0%) who achieved PASI 100 at OLE entry, 209 (65.3%) maintained PASI 100 through week 304 by mNRI (LOCF, 80.6%; OC, 79.9%). Mean PASI improvement from baseline was generally consistent from OLE entry (95.6% for both LOCF and OC) through week 304 (LOCF, 95.9%; OC, 96.5%).
Conclusion: In this 304-week interim analysis of continuous risankizumab treatment, the safety profile was consistent with previous interim analyses from the LIMMitless study. With continuous risankizumab treatment, most patients maintained PASI 90 or PASI 100 responses from OLE entry through 252 additional weeks in the LIMMitless study.
2. Puig L. Expert Rev Clin Immunol. 2017;13:525–34.
3. Skyrizi® (risankizumab-rzaa). Package insert. AbbVie Inc.; May 2023. Accessed August 23, 2023. https://www.rxabbvie.com/pdf/skyrizi_pi.pdf
4. Gooderham M, et al. J Eur Acad Dermatol Venereol. 2022;36;855–65.
5. Papp KA, et al. J Drugs Dermatol. 2020;19:571–2.