ACR 2019

ACR/ARP HIGHLIGHTS

Conference summaries


Spondyloarthritis Including Psoriatic Arthritis

Ixekizumab in Non-Radiographic Axial Spondyloarthritis: Primary Results from a Phase 3 Trial

Presented by: Atul Deodhar, MD, MRCP
Oregon Health & Science University, Portland, OR, USA
  • Ixekizumab is superior to placebo in improving signs, symptoms, and inflammation on MRI in patients with nr-axSpA when added to conventional background medication.

Ixekizumab (IXE) is a high affinity IL-17A monoclonal antibody that has previously shown efficacy in AS/radiographic-axial spondyloarthritis (r-axSpA). [1,2] COAST-X (NCT02757352) is a phase 3 study that assessed efficacy and safety of IXE in patients (pts) with active non-radiographic-axial spondyloarthritis (nr-axSpA) and objective signs of inflammation.

  • To report primary and secondary efficacy and safety outcomes of the COAST-X phase 3 trial at week 16 and week 52.
  • COAST-X was a 52-week, randomized, double-blind, placebo (PBO)-controlled study enrolling adults with an established diagnosis of axSpA who met ASAS (but not modified New York) criteria, had BASDAI ≥4, sacroiliitis on magnetic resonance imaging [MRI] or elevated CRP >5 mg/L), and inadequate response or intolerance to NSAIDs.
  • Patients were randomized 1:1:1 to 80 mg IXE every 4 weeks (Q4W), 80 mg IXE every 2 weeks (Q2W), or PBO.
  • Changes to conventional background medication (NSAIDs, csDMARDs, analgesics, and low dose corticosteroids) as well as escape to open label (OL) IXE Q2W were allowed at investigator discretion after week 16.
  • A logistic regression model with non-responder imputation was used for categorical data; a mixed effects model of repeated measures was used for continuous variables; analysis of covariance was used for sacroiliac joint (SIJ) MRI SPARCC (Spondyloarthritis Research Consortium of Canada) scores.

Primary endpoint

  • ASAS40 at week 16 (US regulatory endpoint) or week 52.
  • A total of 303 subjects were randomized: PBO (N=105), IXE Q4W (N=96), IXE Q2W (N=102).
  • The difference of patients achieving ASAS40 with both IXE regimens vs. PBO was observed as early as week 1.
  • Significantly more pts in the IXE groups compared to the PBO group achieved ASAS40 at week 16: IXE Q2W (40%), IXE Q4W (35%) vs. PBO (19%, p <0.01) and at week 52: IXE Q2W (31%), IXE Q4W (30%) vs. PBO (13%, p <0.01) (Figure).
  • Compared to PBO, pts on either IXE regimen had significantly greater changes from baseline at week 16 and week 52 with regard to disease activity, functional status, and SIJ SPARCC scores.
  • A notable proportion of patients who escaped to OL IXE Q2W had ASAS40 response at the time of escape (16.7%, 25%, and 6.5% on IXE Q2W, IXEQ4W, and PBO, respectively), and ASA40 rates further increased on OL IXE Q2.
  • The frequency of serious adverse events and adverse events that led to treatment discontinuation was low and similar across all arms; no new safety signal was identified.
  • The primary endpoint of ASAS40 and all major secondary endpoints for IXE Q4W and Q2W were met at week 16 and week 52 with no unexpected safety findings.

Key messages/Clinical perspectives

  • IXE added to conventional background medication was superior to PBO in improving signs, symptoms, and inflammation on MRI in patients with nr-axSpA.

 

Trial: NCT02757352



References

References


  1. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. 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. Arthritis Rheumatol. 2019 Apr;71(4):599-611.
  2. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018 Dec 8;392(10163):2441-51.

Presenter disclosure: The presenter has reported relationships with Abbvie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Janssen Research & Development, LLC, Novartis, Pfizer, UCB Pharma.

Written by: Patrick Moore, PhD

Reviewed by: Alessia Alunno, MD, PhD

Local reviewers: Alessia Alunno, MD, PhD (Italian); Aurélie Najm, MD (French); Yukinori Okada, MD, PhD (Japanese); Fabian Proft, MD (German); Javier Rodríguez-Carrio, MD, PhD (Spanish); Priscilla Wong, MD (Chinese)

Scientific Editor:  Leonard H. Calabrese, DO


RHEUMATOID ARTHRITIS

A Comparative Analysis of Upadacitinib Monotherapy and Upadacitinib Combination Therapy for the Treatment of Rheumatoid Arthritis from Two Phase 3 Trials

Presented by: Maya H. Buch, MD, PhD - University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom

Rheumatoid Arthritis Treatment with Filgotinib: Week 156 Safety and Efficacy Data from a Phase 2b Open-Label Extension Study

Presented by: Arthur Kavanaugh, MD - University of California, San Diego School of Medicine, La Jolla, CA, USA

SYSTEMIC LUPUS ERYTHEMATOSUS

A Phase 1b/2a Trial of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus

Presented by: Sarfaraz Hasni, MD - National Institute of Arthritis, Musculoskeletal, and Skin diseases/ National Institutes of Health, Bethesda, MD, USA

A Phase 3 Randomized Controlled Trial of Anifrolumab in Patients with Moderate to Severe Systemic Lupus Erythematosus

Presented by: Richard A. Furie, MD - Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA

EPIDEMIOLOGY AND PUBLIC HEALTH

The Burden of Comorbidity in Patients with RA, PsA or SPA in a General Practice Registry

Presented by: Diederik De Cock, PhD - KU Leuven, Leuven, Belgium

SJÖGREN’S SYNDROME

SPONDYLOARTHRITIS INCLUDING PSORIATIC ARTHRITIS

Ixekizumab Demonstrates Improvement Comparable to Adalimumab Across ACR Components in Biologic-Naïve Patients with Psoriatic Arthritis

Presented by: M. Elaine Husni, MD, MPH - Dept. of Rheumatologic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA

Tildrakizumab Efficacy on Psoriasis in Patients with Psoriatic Arthritis—An Analysis from a Phase 2 Study

Presented by: Alan M. Mendelsohn, MD - Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA, Princeton, NJ, USA

Development of a Set of ASAS Quality Standards for Adults with Axial Spondyloarthritis

Presented by: Uta Kiltz, MD - Rheumazentrum Ruhrgebiet/Ruhr University Bochum, Herne, Germany

Ixekizumab in Non-Radiographic Axial Spondyloarthritis: Primary Results from a Phase 3 Trial

Presented by: Atul Deodhar, MD, MRCP - Oregon Health & Science University, Portland, OR, USA

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