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Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis
  1. Margreet Kloppenburg1,
  2. Charles Peterfy2,
  3. Ida K Haugen3,
  4. Féline Kroon1,
  5. Su Chen4,
  6. Li Wang5,
  7. Wei Liu6,
  8. Gwen Levy7,
  9. Roy M Fleischmann8,
  10. Francis Berenbaum9,
  11. Désirée van der Heijde1,
  12. Prashant Bansal10,
  13. Ruth Wittoek11,
  14. Sheng Feng12,
  15. Yuni Fang13,
  16. Mary Saltarelli13,
  17. Jeroen K Medema14,
  18. Marc C Levesque14
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Spire Sciences, Boca Raton, Florida, USA
  3. 3 Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  4. 4 Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA
  5. 5 Development Design Center, AbbVie, North Chicago, Illinois, USA
  6. 6 Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA
  7. 7 Pharmacovigilance and Patient Safety, AbbVie, North Chicago, Illinois, USA
  8. 8 Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Metroplex Clinical Research Center, Dallas, Texas, USA
  9. 9 Department of Rheumatology, Sorbonne Universités and Inserm, DHU i2B, APHP, Hospital Saint-Antoine, Paris, France
  10. 10 Scientific and Medical Services, PAREXEL, Waltham, Massachusetts, USA
  11. 11 Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
  12. 12 Exploratory Statistics, Data Science and Statistics, AbbVie, North Chicago, Illinois, USA
  13. 13 Drug Metabolism, Pharmacokinetics and Bioanalysis, AbbVie, North Chicago, Illinois, USA
  14. 14 Immunology Development, AbbVie, North Chicago, Illinois, USA
  1. Correspondence to Professor Margreet Kloppenburg, Department of Rheumatology, Leiden University Medical Center, Postbox 9600, Leiden 2300 RC, The Netherlands; g.kloppenburg{at}lumc.nl

Abstract

Objective To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA).

Methods Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates.

Results Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI –1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1α and IL-1β levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67).

Conclusion Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.

  • DMOADs (biologic)
  • hand osteoarthritis
  • interleukin-1
  • inflammation

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Footnotes

  • Handling editor Josef S Smolen

  • Presented at The results of this study were presented in part at the OARSI World Congress on Osteoarthritis (27–30 April 2017; Las Vegas, Nevada), the European League Against Rheumatism Congress (14–17 June 2017; Madrid, Spain) and the American College of Rheumatology Annual Meeting (4–8 November 2017; San Diego, California).

  • Contributors All authors contributed to the development of the content. All authors and AbbVie reviewed and approved the final manuscript, and the authors maintained control over the final content.

  • Funding AbbVie funded this study (NCT02384538). AbbVie funded the medical writing support.

  • Competing interests AbbVie contributed to the design of the study and was involved in the collection, analysis and interpretation of the data, and in the writing, review and approval of the publication. MK has received grant/research support from Pfizer and been a consultant for AbbVie, GlaxoSmithKline, Merck and Levicept. CP is an employee of Spire Sciences, and is on the speakers' bureau for Amgen and Bristol-Myers Squibb. IKH has been a consultant for AbbVie. FK has no conflicts of interest to declare. RMF has received grant/research support from and has been a consultant for AbbVie. FB has been a consultant for AbbVie, Pfizer and Regeneron. DvdH has been a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; she is Director of Imaging Rheumatology. PB is a former employee of PAREXEL, which performed work for this study under contract to AbbVie. RW has been a consultant for AbbVie. SC, LW, WL, GL, YF, MS, JKM and MCL are employees of AbbVie and may own AbbVie stock and/or stock options. SF is a former employee of AbbVie and may own AbbVie stock and/or stock options.

  • Patient consent Not required.

  • Ethics approval The protocol was approved by institutional review boards at each study site.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymised, individual and trial-level data (analysis data sets), as well as other information (eg, protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

  • Author note PB was affiliated to Scientific and Medical Services, PAREXEL, and SF was affiliated to Exploratory Statistics, Data Science and Statistics, AbbVie, at the time of this study.

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