Abstract
Background: Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. Methods: IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16–44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. Findings: Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5–32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6–30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9–61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. Interpretation: Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis. Funding: AbbVie and Boehringer Ingelheim.
| Original language | English |
|---|---|
| Journal | The Lancet |
| Volume | 394 |
| Issue number | 10198 |
| Pages (from-to) | 576-586 |
| Number of pages | 11 |
| ISSN | 0140-6736 |
| DOIs | |
| Publication status | Published - 17.08.2019 |
Funding
Boehringer Ingelheim contributed to study design and participated in data collection. AbbVie did data analysis and interpretation. The funders participated in writing, review, and approval of the manuscript. All authors had full access to the data, reviewed and approved the final version, and were responsible for the decision to submit the manuscript for publication. A medical writer, funded by AbbVie, assisted with manuscript preparation under the authors' direction. KR has served as adviser, paid speaker, or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, Leo, Lilly, Medac, Merck Sharp & Dohme, Novartis, Miltenyi Biotec, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Takeda, UCB, Valeant, and Xenoport. MG has received grant or research support from AbbVie, Akros, Arcutis, Boehringer Ingelheim, BMS, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Kyowa Kirin, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, UCB, and Valeant; has participated in a speaker's bureau for AbbVie, Actelion, Celgene, Eli Lilly, Galderma, Janssen, Novartis, Pfizer, Regeneron, and Sanofi Genzyme; and has served as a consultant for AbbVie, Amgen, Arcutis, Akros, Boehringer Ingelheim, Celgene, Kyowa Kirin, Novartis, Pfizer, Sanofi Genzyme, and Sun Pharmaceuticals. DT has received grant or research support from AbbVie, Celgene, and Novartis; has participated in a speaker's bureau for AbbVie, Almirall, Celgene, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz/Hexal, Sanofi, and UCB; and has served as a consultant for AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz/Hexal, Sanofi, and UCB. JJC has received compensation as a speaker, consultant, and investigator for AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Regeneron, Sanofi-Aventis, Sun Pharma, and UCB. He has been an investigator for Merck, Maruho, Pfizer, Regeneron, Boehringer Ingelheim, MC-2, Verrica, and Sandoz. CR has received compensation as a speaker or consultant, or adviser for AbbVie, Janssen, Leo, Lilly, Novartis, and UCB, and has served as a consultant or adviser for AbbVie, Boehinger Ingelheim Dermira, Dr Reddys, Janssen, Leo, Lilly, Novartis, Regeneron-Sanofi, and UCB. JGK has received honoraria and consulting fees paid to Rockefeller University from AbbVie, Acros, Amgen, BMS, BiogenMA, Boehringer, Innovoderm, Janssen, Kineta, Leo Pharma, Novan, Novartis, Paraxel, Pfizer, Regeneron, Sienna, UCB, and Vitae, and has received consulting fees from Allergan, Asana, Aurigene, BiogenIdec, Escalier, Lilly, Roche, and Valent. T-FT has served as a consultant for AbbVie, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen-Cilag, Novartis International AG, and Pfizer. MF is a full-time employee of Boehringer Ingelheim and might hold stock or stock options. YG and DAW are full-time employees of AbbVie and might hold stock or stock options. EHZT was a full-time employee of AbbVie when the study was done and might hold stock or stock options. CP has received grants or research support from Pierre Fabre and Sanofi-Regeneron and has served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen Cilag, Leo, Lilly, Pfizer, Novartis, Pierre Fabre, Sanofi, and UCB. AbbVie and the authors thank the patients who participated in this clinical trial and all study investigators for their contributions. Medical writing assistance (funded by AbbVie) was provided by Fran Karo, Richard T Porter, and Lamara D Shrode of JB Ashtin, who, on behalf of the authors, assisted in writing the first draft, implemented author revisions throughout the editorial process, and prepared the manuscript for submission. Statistical analyses were supported by Ziqian Geng and Tianshuang Wu, AbbVie Data and Statistical Sciences (North Chicago, IL, USA).
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
