Kim A Papp1, Andrew Blauvelt1, Michael Bukhalo1, Melinda Gooderham1, James G Krueger1, Jean-Philippe Lacour1, Alan Menter1, Sandra Philipp1, Howard Sofen1, Stephen Tyring1, Beate R Berner1, Sudha Visvanathan1, Chandrasena Pamulapati1, Nathan Bennett1, Mary Flack1, Paul Scholl1, Steven J Padula1. 1. From K. Papp Clinical Research and Probity Medical Research, Waterloo, ON (K.A.P.), School of Medicine, Queen's University, Kingston, ON (M.G.), and Centre for Dermatology and Probity Medical Research, Peterborough, ON (M.G.) - all in Canada; Oregon Medical Research Center, Portland (A.B.); Altman Dermatology Associates, Arlington Heights, IL (M.B.); Rockefeller University, New York (J.K.); Hôpital de l'Archet, University of Nice-Sophia Antipolis, Nice, France (J.-P.L.); Baylor Research Institute, Dallas (A.M.); Charité Universitätsmedizin Berlin, Berlin (S.P.), Boehringer Ingelheim Pharma, Biberach (B.R.B.), and Boehringer Ingelheim Pharma, Ingelheim, (S.J.P.) - all in Germany; University of Texas Health Science Center, Houston (S.T.); University of California, Los Angeles, School of Medicine, Los Angeles (H.S.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (S.V., C.P., N.B., M.F., P.S.).
Abstract
BACKGROUND: Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: We randomly assigned a total of 166 patients to receivesubcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. RESULTS: At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. CONCLUSIONS: In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).
RCT Entities:
BACKGROUND:Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. RESULTS: At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. CONCLUSIONS: In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).
Authors: Amit Khatri; Ling Cheng; Anne Camez; Stanislav Ignatenko; Yinuo Pang; Ahmed A Othman Journal: Clin Pharmacokinet Date: 2019-06 Impact factor: 6.447
Authors: James Buxbaum; Michael Quezada; Bradford Chong; Nikhil Gupta; Chung Yao Yu; Christianne Lane; Ben Da; Kenneth Leung; Ira Shulman; Stephen Pandol; Bechien Wu Journal: Am J Gastroenterol Date: 2018-03-15 Impact factor: 10.864