ACR 2019

ACR/ARP HIGHLIGHTS

Conference summaries


Spondyloarthritis Including Psoriatic Arthritis

Dual Neutralization of IL-17A and IL-17F with Bimekizumab in Patients with Active Ankylosing Spondylitis: 48-Week Efficacy and Safety Results from a Phase 2b, Randomized, Blinded, Placebo-Controlled, Dose-Ranging Study

Presented by: Désirée van der Heijde, MD, PhD
Leiden University Medical Center, Leiden, Netherlands
  • Bimekizumab led to rapid clinical improvement that was sustained up to week 48 in patients with AS.
  • Bimekizumab was generally well tolerated and no new or unexpected safety findings were observed.

The monoclonal antibody bimekizumab potently and selectively neutralizes both IL-17A and IL-17F and showed promising results in early clinical trials as a novel therapeutic approach to ankylosing spondylitis (AS). [1] In a 12-week study, dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings. Herein, the 48-week efficacy and safety of bimekizumab in patients with active AS are reported.

  • Eligible patients with active AS (Bath AS Disease Activity Index (BASDAI) ≥4; spinal pain ≥4 (0–10)) who fulfilled the modified New York criteria with inadequate response/intolerance to NSAIDs were randomized 1:1:1:1:1 to sc bimekizumab 16 mg, 64 mg, 160 mg, 320 mg, or placebo every 4 weeks, for 12 weeks (double-blind period).
  • Subsequently, patients in the 16 mg, 64 mg, and placebo groups were re-randomized 1:1 to sc bimekizumab 160 mg or 320 mg every 4 weeks through week 48; dosing in the original 160 mg and 320 mg groups was unchanged through week 48 (dose-blind period).
  • Efficacy endpoints included ASAS20, ASAS40, ASAS5/6, ASAS partial remission, and AS Disease Activity Score with C-reactive Protein (ASDAS-CRP); data presented for all pts who began the dose-blind period and received ≥1 dose of study drug.
  • Non-responder imputation accounted for missing binary scores; multiple imputation accounted for missing continuous values.

Primary endpoint

  • The primary endpoint was ASAS40 response rate at week 12.
  • Of 303 randomized patients, 87.5% completed the 48-week treatment period.
  • Patients had similar baseline characteristics across treatment groups.
  • At week 12, significantly more bimekizumab-treated patients vs placebo achieved ASAS40 (16 mg 29.5%; 64 mg 42.6%; 160 mg 46.7%; 320 mg 45.9%; placebo 13.3%; p <0.05, all doses).
  • ASAS40 response rates increased up to week 24 and were maintained up to week 48 (35.5–64.0%) (Figure).
  • Improvements observed at week 12 in other efficacy endpoints were sustained to week 48: ASAS20 51.9–80.0%, ASAS5/6 41.9–80.0%, ASAS partial remission 20.6–34.4%.
  • At week 12, mean improvement from baseline in ASDAS-CRP scores were from –0.3 to –1.7; scores improved further from baseline and were maintained to week 48: from –1.6 to –2.0.
  • During the 48-week treatment period, bimekizumab was generally well tolerated.
  • Treatment-emergent adverse events (TEAEs) were reported by 77.6% of patients in both dose groups of bimekizumab; 6.6% discontinued due to TEAEs.
  • The most commonly reported TEAEs were nasopharyngitis, bronchitis, and pharyngitis.
    • Irritable bowel disease was reported by 1.3% of patients; no TEAEs of suicidal ideation were reported.
    • Serious infections were reported in 1.3% of patients.
  • One death was observed (cardiac arrest, 160 mg group, double-blind period), but was judged unrelated to study drug by the investigator.
  • Following positive results at week 12, bimekizumab showed sustained improvements in patients with active AS across multiple measures of disease activity up to week 48.
  • Bimekizumab was generally well tolerated and no new or unexpected safety findings were identified.

Key messages/Clinical perspectives

  • These data provide evidence that neutralizing both IL-17F and IL17A with bimekizumab may be a promising therapeutic option for patients with AS, warranting further investigation across the entire spectrum of spondyloarthropathies.

 

Trial: NCT02963506



References

References


  1. Van der Heijde D, Gensler LS, Deodhar A, et al. EULAR 2018 - LB0001. Dual neutralisation of il-17A and il-17F with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis 2018;77(Suppl. 2):A70

Presenter disclosure: The presenter has reported relationships with AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo Smith and Klein, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB.

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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