Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase III Randomized, Double‐Blind, Placebo‐Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors. Issue 4 (8th March 2019)

• Record Type: Journal Article
• Authors: Deodhar, Atul; Poddubnyy, Denis; Pacheco‐Tena, Cesar; Salvarani, Carlo; Lespessailles, Eric; Rahman, Proton; Järvinen, Pentti; Sanchez‐Burson, Juan; Gaffney, Karl; Lee, Eun Bong; Krishnan, Eswar; Santisteban, Silvia; Li, Xiaoqi; Zhao, Fangyi; Carlier, Hilde; Reveille, John D.
• Other Names: Antolini Christopher investigator.; Azevedo Valderilio investigator.; Barkham Magnus investigator.; Rodriguez Aaron Alejandro Barrera investigator.; Berman Alberto investigator.; Blicharski Tomasz investigator.; Brzezicki Jan investigator.; Burmester Gerd investigator.; Carrio Judith investigator.; Collantes Eduardo investigator.; Combe Bernard investigator.; Cons‐Molina Fidencio investigator.; Cortes‐Maisonet Gregorio investigator.; Dudek Anna investigator.; Barragan Sergio Duran investigator.; Elkayam Ori investigator.; Flint Kathleen investigator.; Galeazzi Mauro investigator.; Gaylis Norman investigator.; Goddard David investigator.; Fernandez Carlos Gonzalez investigator.; Goupille Philippe investigator.; Masmitja Jordi Gratacos investigator.; Greenwald Maria investigator.; Gremese Elisa investigator.; Hong Seung Jae investigator.; Howell Mary investigator.; Hrycaj Pawel investigator.; Ince Akgun investigator.; Ju Ji Hyeon investigator.; Kaine Jeffrey investigator.; Kang Seong Wook investigator.; Keiserman Mauro investigator.; Kim Tae‐Hwan investigator.; Kivitz Alan investigator.; Klein Steven investigator.; Kremer Joel investigator.; Lee Sang Heon investigator.; Lee Chang Keun investigator.; Lee Sang‐Hoon investigator.; Lidman Roger investigator.; Loveless James investigator.; Lucero Eleonora investigator.; Cocco Jose Maldonado investigator.; Marcolino Flora investigator.; Mariette Xavier investigator.; Mehta Daksha investigator.; Morin Frederic investigator.; Moscovici Yolanda investigator.; Mueller Eric investigator.; Mysler Eduardo investigator.; Blasco Francisco Navarro investigator.; Nguyen Minh investigator.; Pantojas Carlos investigator.; Park Min‐Chan investigator.; Jesus Amarilis Perez‐De investigator.; Peters Eric investigator.; Plebanski Rafal investigator.; Querubin Roel investigator.; Remus Cesar Ramos investigator.; Reitblat Tatiana investigator.; Rivera Tania investigator.; Rodriguez Juan Cruz Rizo investigator.; Sayers Michael investigator.; Scotton Antonio investigator.; Scoville Craig investigator.; Shaw David investigator.; Shin Kichul investigator.; Singhal Atul investigator.; Skinner Cassandra investigator.; Soto‐Raices Oscar investigator.; Soubrier Martin investigator.; Szymanska Malgorzata investigator.; Thai Christine investigator.; van de Sande Marleen investigator.; Wells Alvin investigator.; Wojciechowski Rafal investigator.; Xavier Ricardo investigator.; Ximenes Antonio investigator.; Zisman Devy investigator.;
• Is Part Of: Arthritis & rheumatology. Volume 71:Issue 4(2019)
• Page Start: 599
• Page End: 611
• Publication Date: 2019-03-08
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.40753
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double‐blind, placebo‐controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80‐mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80‐mg or 160‐mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.