Désirée van der Heijde1, James Cheng-Chung Wei2, Maxime Dougados3, Philip Mease4, Atul Deodhar5, Walter P Maksymowych6, Filip Van den Bosch7, Joachim Sieper8, Tetsuya Tomita9, Robert Landewé10, Fangyi Zhao11, Eswar Krishnan11, David H Adams11, Beth Pangallo11, Hilde Carlier11. 1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands. Electronic address: mail@dvanderheijde.nl. 2. Institute of Medicine, Chung Shan Medical University, Department of Internal Medicine, Chung Shan Medical University Hospital, Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. 3. Department of Rheumatology, Hôpital Cochin, Paris, France. 4. Swedish Medical Center and University of Washington, Seattle, WA, USA. 5. Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA. 6. Department of Medicine, University of Alberta, Edmonton, AB, Canada. 7. Department of Rheumatology, Ghent University Hospital, Ghent, Belgium. 8. Department of Rheumatology, Charite University Hospital, Berlin, Germany. 9. Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 10. Amsterdam Rheumatology and Clinical Immunology Center, Amsterdam, Netherlands; Zuyderland Medical Center, Heerlen, Netherlands. 11. Eli Lilly and Company, Indianapolis, IN, USA.
Abstract
BACKGROUND:Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. METHODS: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. FINDINGS:Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumabgroup (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. INTERPRETATION: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. FUNDING: Eli Lilly and Company.
RCT Entities:
BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. METHODS: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. FINDINGS: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. INTERPRETATION: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. FUNDING: Eli Lilly and Company.
Authors: Eric Gracey; Lars Vereecke; Dermot McGovern; Mareike Fröhling; Georg Schett; Silvio Danese; Martine De Vos; Filip Van den Bosch; Dirk Elewaut Journal: Nat Rev Rheumatol Date: 2020-07-13 Impact factor: 20.543
Authors: Michael M Ward; Atul Deodhar; Lianne S Gensler; Maureen Dubreuil; David Yu; Muhammad Asim Khan; Nigil Haroon; David Borenstein; Runsheng Wang; Ann Biehl; Meika A Fang; Grant Louie; Vikas Majithia; Bernard Ng; Rosemary Bigham; Michael Pianin; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Jeff Oristaglio; Amy Turner; Walter P Maksymowych; Liron Caplan Journal: Arthritis Care Res (Hoboken) Date: 2019-08-21 Impact factor: 4.794