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OP0168 A phase 2a, placebo-controlled, randomized study of ABT-981, an anti-interleukin-1ALPHA and -1BETA dual variable domain immunoglobulin, to treat erosive hand osteoarthritis (EHOA)
  1. M Kloppenburg1,
  2. C Peterfy2,
  3. IK Haugen3,
  4. F Kroon1,
  5. S Chen4,
  6. L Wang4,
  7. W Liu4,
  8. G Levy4,
  9. R Fleischmann5,
  10. F Berenbaum6,
  11. D van der Heijde1,
  12. J Medema4,
  13. MC Levesque4
  1. 1Leiden University Medical Center, Leiden, Netherlands
  2. 2Spire Sciences, Inc., Boca Raton, FL, United States
  3. 3Diakonhjemmet Hospital, Oslo, Norway
  4. 4AbbVie Inc., North Chicago, IL
  5. 5University of Texas Southwestern Medical Center at Dallas, Metroplex Clinical Research Center, Dallas, TX, United States
  6. 6University Pierre & Marie Curie and Inserm, DHU i2B, APHP, Hospital Saint-Antoine, Paris, France

Abstract

Background No approved OA therapies reduce pain and slow joint damage. Mouse data suggested that inhibiting IL-1α and -1β with ABT-981 would reduce pain and slow structural progression in EHOA.

Objectives To test the efficacy and safety of ABT-981 in EHOA.

Methods Subjects with HOA per ACR criteria, ≥3 inflamed IP joints (tender, swollen, or both), hand pain ≥6 (scale 0–10), and ≥1 erosive IP joint on X-ray (Verbruggen-Veys) were randomized to placebo (PBO) or ABT-981 200 mg SC every 2 wk for 26 wk. The primary outcome was AUSCAN hand pain at 16 wk. Subjects had radiographs of both hands and MRI of the index hand at baseline and 26 wk. Both radiographs (Verbruggen-Veys, GUSS™, OARSI, Kellgren-Lawrence [KL]) and MRIs (HOAMRIS) were read by 2 independent central readers. A modified intent-to-treat population (ie, randomized and treated) was analyzed. Continuous efficacy endpoints were assessed using ANCOVA models with treatment and country as main factors and baseline measurements as covariates with LOCF imputation for the primary endpoint.

Results Of 131 treated subjects (85% women; mean age 66 y), 61/67 randomized to PBO and 49/64 to ABT-981 completed the study; subject characteristics were well matched. AUSCAN pain was not significantly different vs PBO at wk 16 (P=0.39; Table 1, Figure); X-ray data and other endpoints also were not statistically different vs PBO (Table 1). ABT-981 significantly decreased hsCRP, neutrophils, IL-1α, and IL-1β. Immunogenicity had no impact on ABT-981 pharmacokinetics. Besides injection site reactions and neutropenia, ABT-981 was well tolerated and safety was similar vs PBO, with no serious infections (Table 2).

Table 1
Table 2

Conclusions Despite adequate pharmacodynamics results, targeting IL-1 may be ineffective in EHOA, as ABT-981 did not improve outcomes.

Acknowledgements AbbVie funded the study (NCT02384538); participated in study design, data collection, analysis, and interpretation and in abstract writing, review, and approval; and funded writing support by M. Theisen of CPS.

Disclosure of Interest M. Kloppenburg Grant/research support from: Pfizer, Consultant for: AbbVie, GlaxoSmithKline, Merck, Levicept, C. Peterfy Shareholder of: Spire Sciences, Inc. (which provides imaging services for clinical trials to multiple pharmaceutical companies), Employee of: Spire Sciences, Inc. (which provides imaging services for clinical trials to multiple pharmaceutical companies), Speakers bureau: Amgen, I. Haugen Consultant for: AbbVie, F. Kroon: None declared, S. Chen Shareholder of: AbbVie, Employee of: AbbVie, L. Wang Shareholder of: AbbVie, Employee of: AbbVie, W. Liu Shareholder of: AbbVie, Employee of: AbbVie, G. Levy Shareholder of: AbbVie, Employee of: AbbVie, R. Fleischmann Grant/research support from: AbbVie, Consultant for: AbbVie, F. Berenbaum Consultant for: AbbVie, Pfizer, Regeneron, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Employee of: Director of Imaging Rheumatology bv., J. Medema Shareholder of: AbbVie, Employee of: AbbVie, M. Levesque Shareholder of: AbbVie, Employee of: AbbVie

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