PMID- 30343531 OWN - NLM STAT- MEDLINE DCOM- 20191227 LR - 20200309 IS - 2326-5205 (Electronic) IS - 2326-5191 (Print) IS - 2326-5191 (Linking) VI - 71 IP - 4 DP - 2019 Apr TI - 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. PG - 599-611 LID - 10.1002/art.40753 [doi] AB - 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. CI - (c) 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. FAU - Deodhar, Atul AU - Deodhar A AD - Oregon Health & Science University, Portland. FAU - Poddubnyy, Denis AU - Poddubnyy D AUID- ORCID: 0000-0002-4537-6015 AD - Universitatsmedizin Berlin and German Rheumatism Research Centre, Berlin, Germany. FAU - Pacheco-Tena, Cesar AU - Pacheco-Tena C AD - Universidad Autonoma de Chihuahua, Chihuahua, Deodhar Mexico. FAU - Salvarani, Carlo AU - Salvarani C AD - Azienda USL-IRCCS di Reggio Emilia and Universita' di Modena e Reggio Emilia, Reggio Emilia, Italy. FAU - Lespessailles, Eric AU - Lespessailles E AD - University of Orleans, Orleans, France. FAU - Rahman, Proton AU - Rahman P AD - Memorial University, St. John's, Newfoundland, Canada. FAU - Jarvinen, Pentti AU - Jarvinen P AD - Kiljava Medical Research, Hyvinkaa, Finland. FAU - Sanchez-Burson, Juan AU - Sanchez-Burson J AD - Hospital Infanta Luisa, Seville, Spain. FAU - Gaffney, Karl AU - Gaffney K AD - Norfolk and Norwich Hospital NHS Foundation Trust and University of East Anglia, Norwich, UK. FAU - Lee, Eun Bong AU - Lee EB AD - Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Krishnan, Eswar AU - Krishnan E AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Santisteban, Silvia AU - Santisteban S AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Li, Xiaoqi AU - Li X AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Zhao, Fangyi AU - Zhao F AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Carlier, Hilde AU - Carlier H AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Reveille, John D AU - Reveille JD AD - University of Texas-McGovern Medical School, Houston. CN - COAST-W Study Group LA - eng SI - ClinicalTrials.gov/NCT02696798 GR - Eli Lilly and Company/International GR - UL1 TR000371/TR/NCATS NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190308 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Tumor Necrosis Factor Inhibitors) RN - BTY153760O (ixekizumab) SB - IM MH - Adult MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antirheumatic Agents/*therapeutic use MH - Axis, Cervical Vertebra/diagnostic imaging MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Quality of Life MH - Radiography MH - Spine/diagnostic imaging MH - Spondylarthritis/diagnostic imaging/*drug therapy MH - Treatment Outcome MH - Tumor Necrosis Factor Inhibitors/therapeutic use PMC - PMC6593790 FIR - Antolini, Christopher IR - Antolini C FIR - Azevedo, Valderilio IR - Azevedo V FIR - Barkham, Magnus IR - Barkham M FIR - Rodriguez, Aaron Alejandro Barrera IR - Rodriguez AAB FIR - Berman, Alberto IR - Berman A FIR - Blicharski, Tomasz IR - Blicharski T FIR - Brzezicki, Jan IR - Brzezicki J FIR - Burmester, Gerd IR - Burmester G FIR - Carrio, Judith IR - Carrio J FIR - Collantes, Eduardo IR - Collantes E FIR - Combe, Bernard IR - Combe B FIR - Cons-Molina, Fidencio IR - Cons-Molina F FIR - Cortes-Maisonet, Gregorio IR - Cortes-Maisonet G FIR - Dudek, Anna IR - Dudek A FIR - Barragan, Sergio Duran IR - Barragan SD FIR - Elkayam, Ori IR - Elkayam O FIR - Flint, Kathleen IR - Flint K FIR - Galeazzi, Mauro IR - Galeazzi M FIR - Gaylis, Norman IR - Gaylis N FIR - Goddard, David IR - Goddard D FIR - Fernandez, Carlos Gonzalez IR - Fernandez CG FIR - Goupille, Philippe IR - Goupille P FIR - Masmitja, Jordi Gratacos IR - Masmitja JG FIR - Greenwald, Maria IR - Greenwald M FIR - Gremese, Elisa IR - Gremese E FIR - Hong, Seung Jae IR - Hong SJ FIR - Howell, Mary IR - Howell M FIR - Hrycaj, Pawel IR - Hrycaj P FIR - Ince, Akgun IR - Ince A FIR - Ju, Ji Hyeon IR - Ju JH FIR - Kaine, Jeffrey IR - Kaine J FIR - Kang, Seong Wook IR - Kang SW FIR - Keiserman, Mauro IR - Keiserman M FIR - Kim, Tae-Hwan IR - Kim TH FIR - Kivitz, Alan IR - Kivitz A FIR - Klein, Steven IR - Klein S FIR - Kremer, Joel IR - Kremer J FIR - Lee, Sang Heon IR - Lee SH FIR - Lee, Chang Keun IR - Lee CK FIR - Lee, Sang-Hoon IR - Lee SH FIR - Lidman, Roger IR - Lidman R FIR - Loveless, James IR - Loveless J FIR - Lucero, Eleonora IR - Lucero E FIR - Cocco, Jose Maldonado IR - Cocco JM FIR - Marcolino, Flora IR - Marcolino F FIR - Mariette, Xavier IR - Mariette X FIR - Mehta, Daksha IR - Mehta D FIR - Morin, Frederic IR - Morin F FIR - Moscovici, Yolanda IR - Moscovici Y FIR - Mueller, Eric IR - Mueller E FIR - Mysler, Eduardo IR - Mysler E FIR - Blasco, Francisco Navarro IR - Blasco FN FIR - Nguyen, Minh IR - Nguyen M FIR - Pantojas, Carlos IR - Pantojas C FIR - Park, Min-Chan IR - Park MC FIR - Jesus, Amarilis Perez-De IR - Jesus AP FIR - Peters, Eric IR - Peters E FIR - Plebanski, Rafal IR - Plebanski R FIR - Querubin, Roel IR - Querubin R FIR - Remus, Cesar Ramos IR - Remus CR FIR - Reitblat, Tatiana IR - Reitblat T FIR - Rivera, Tania IR - Rivera T FIR - Rodriguez, Juan Cruz Rizo IR - Rodriguez JCR FIR - Sayers, Michael IR - Sayers M FIR - Scotton, Antonio IR - Scotton A FIR - Scoville, Craig IR - Scoville C FIR - Shaw, David IR - Shaw D FIR - Shin, Kichul IR - Shin K FIR - Singhal, Atul IR - Singhal A FIR - Skinner, Cassandra IR - Skinner C FIR - Soto-Raices, Oscar IR - Soto-Raices O FIR - Soubrier, Martin IR - Soubrier M FIR - Szymanska, Malgorzata IR - Szymanska M FIR - Thai, Christine IR - Thai C FIR - van de Sande, Marleen IR - van de Sande M FIR - Wells, Alvin IR - Wells A FIR - Wojciechowski, Rafal IR - Wojciechowski R FIR - Xavier, Ricardo IR - Xavier R FIR - Ximenes, Antonio IR - Ximenes A FIR - Zisman, Devy IR - Zisman D EDAT- 2018/10/22 06:00 MHDA- 2019/12/28 06:00 PMCR- 2019/06/26 CRDT- 2018/10/22 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2018/10/03 00:00 [accepted] PHST- 2018/10/22 06:00 [pubmed] PHST- 2019/12/28 06:00 [medline] PHST- 2018/10/22 06:00 [entrez] PHST- 2019/06/26 00:00 [pmc-release] AID - ART40753 [pii] AID - 10.1002/art.40753 [doi] PST - ppublish SO - Arthritis Rheumatol. 2019 Apr;71(4):599-611. doi: 10.1002/art.40753. Epub 2019 Mar 8.