Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials

• Published in: The Lancet (British edition) 2018-08, Vol.392 (10148), p.650-661
• Main Authors: Gordon, Kenneth B, Strober, Bruce, Lebwohl, Mark, Augustin, Matthias, Blauvelt, Andrew, Poulin, Yves, Papp, Kim A, Sofen, Howard, Puig, Lluís, Foley, Peter, Ohtsuki, Mamitaro, Flack, Mary, Geng, Ziqian, Gu, Yihua, Valdes, Joaquin M, Thompson, Elizabeth H Z, Bachelez, Hervé
• Format: Article
• Language: English
• Subjects: Active control; Adult; Analysis; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Clinical trials; Cytokines; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Dermatologic Agents - pharmacology; Double-Blind Method; Double-blind studies; Effectiveness; Evidence-based medicine; Female; Gangrene; Humans; Immunoglobulin G; Immunoglobulin G - therapeutic use; Immunotherapy; Infections; Inflammatory bowel disease; Injections, Subcutaneous - methods; Interleukin 23; Interleukin-12 - metabolism; Interleukin-23 Subunit p19 - drug effects; Interleukin-23 Subunit p19 - metabolism; Male; Melanoma; Middle Aged; Monoclonal antibodies; Motivation; Patients; Placebos; Psoriasis; Psoriasis - drug therapy; Psoriasis - ethnology; Quality of life; Randomization; Safety; Severity of Illness Index; Skin cancer; Skin diseases; TNF inhibitors; Treatment Outcome; Tuberculosis; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Ustekinumab - administration & dosage; Ustekinumab - adverse effects; Ustekinumab - pharmacology; Weight
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(18)31713-6

Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16–52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0–76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7–44·3]; p