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Original research
Changes in selected haematological parameters associated with JAK1/JAK2 inhibition observed in patients with rheumatoid arthritis treated with baricitinib
  1. Jonathan Kay1,2,3,
  2. Masayoshi Harigai4,
  3. Josh Rancourt5,
  4. Christina Dickson5,
  5. Thomas Melby6,
  6. Maher Issa5,
  7. Inmaculada de la Torre5,
  8. Yoshitaka Isaka5,
  9. Anabela Cardoso5,
  10. Chadi Saifan5,
  11. Edward C Keystone7,
  12. Ronald F van Vollenhoven8,
  13. Jon T Giles9,
  14. Tom WJ Huizinga10 and
  15. Joel M Kremer11
  1. 1Division of Rheumatology, Department of Medicine, UMass Memorial Medical Center, Worcester, Massachusetts, USA
  2. 2Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  3. 3Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  4. 4Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
  5. 5Eli Lilly and Company, Indianapolis, Indiana, USA
  6. 6Syneos Health, Morrisville, North Carolina, USA
  7. 7Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, Toronto, Ontario, Canada
  8. 8Department of Rheumatology and Clinical Immunology, Amsterdam Universitair Medische Centra, Amsterdam, The Netherlands
  9. 9Division of Rheumatology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York City, New York, USA
  10. 10Department of Rheumatology, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  11. 11Division of Rheumatology, Department of Medicine, Albany Medical College, Albany, New York, USA
  1. Correspondence to Jonathan Kay; jonathan.kay{at}umassmemorial.org

Abstract

Objective To characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.

Methods Data were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension. Changes in haematological parameters were evaluated up to 128 weeks (N=2387); overall safety of baricitinib was assessed up to 6 years (N=3492).

Results Mean absolute neutrophil counts decreased (−1.36×109/L) within 1 month, followed by stabilisation within the normal reference range through week 128. The incidence of serious infections was not elevated in patients with neutropenia during the 24-week placebo-controlled period. Mean lymphocyte counts increased (+0.30×109/L) within 1 month, then decreased to baseline (weeks 12–24). Mean platelet counts increased at week 2 (+51×109/L), then decreased towards baseline. Overall, mean haemoglobin concentrations decreased (−0.12 mmol/L), then returned to baseline; however, reduced baseline haemoglobin concentrations observed in the highest baseline high-sensitivity C reactive protein quartile increased over time. Permanent drug discontinuation occurred due to laboratory abnormalities related to neutrophil count in 8 (0.2%), lymphocyte counts in 6 (0.2%), platelet counts in 8 (0.2%), and haemoglobin levels in 16 (0.5%) of all baricitinib-treated patients (N=3492 with 7993 total person-years of exposure).

Conclusions Moderate decreases in neutrophils were seen during baricitinib treatment; however, serious infection was uncommon in patients with neutropenia. Transient increases were observed in lymphocytes and platelets, which returned to baseline over time. Changes in haemoglobin concentration were generally small. Haematological abnormalities seldom led to drug discontinuation.

  • Anti-Inflammatory Agents
  • Non-Steroidal
  • Antirheumatic Agents
  • Arthritis
  • Rheumatoid
  • Autoimmune Diseases
  • Inflammation
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Footnotes

  • Twitter Jonathan Kay @RheumKay.

  • Contributors All authors met the following criteria for authorship: substantial contributions to the acquisition, analysis and/or interpretation of data for the work; contribution to drafting the work and/or revising it critically; giving final approval of the version submitted; and agreeing to be accountable for all aspects of the work.

  • Funding The studies were designed by the sponsors, Eli Lilly and Company and Incyte Corporation, with input from an advisory board that included authors of this article who were not employees of Eli Lilly and Company or Incyte Corporation.

  • Competing interests JK reports grants paid to the University of Massachusetts Medical School from AbbVie, Genentech, Gilead Sciences, Pfizer and UCB; and personal fees from AbbVie, Amgen, Alvotech Suisse AG, Arena Pharmaceuticals, Boehringer Ingelheim GmbH, Celltrion Healthcare Co., Janssen Biotech, Merck Sharp & Dohme Corp., Mylan, Novartis AG, Pfizer, Samsung Bioepis, Sandoz and UCB. MH reports grants and personal fees from Bristol-Myers Squibb K.K. and AbbVie Japan; grants from Eisai, Ayumi Pharmaceutical Co., Nippon Kayaku Co., Mitsubishi Tanabe Pharma Co., and Teijin Pharma; and personal fees from Eli Lilly and Company, Boehringer-ingelheim, Kissei Pharmaceutical Co., and Chugai Pharmaceutical Co.. JR, CD, MI, IdlT, YI, AC and CS were employees and shareholders of Eli Lilly and Company. TM was an employee of Syneos Health under contract to Eli Lilly and Company. EK reports grants and personal fees from AbbVie, Amgen, Gilead, Merck, Eli Lilly and Company, Pfizer; grants from PuraPharm; and personal fees from AstraZeneca Pharma, Bristol-Myers Squibb, Celltrion, Jannsen, Myriad Autoimmune, F. Hoffmann-La Roche & Co, Genentech, Sandoz, Sanofi Genzyme, Samsung Bioepsis, and UCB. RFvV reports research support and Grants from Bristol-Myers Squibb, GSK, Eli Lilly and Co., Pfizer, UCB Pharma. Consultancy, honoraria: AbbVie, AstraZeneca, Biotest, Celgene, GlaxoSmithKline, Janssen, Eli Lilly and Co., Novartis, Pfizer, Servier, UCB. JTG reports personal fees from AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., and UCB, and grants from Pfizer. TWJH from the Department of Rheumatology LUMC has received research support/lecture fees/consultancy fees from Abblynx, Merck, UCB, Bristol-Myers Squibb, Biotest AG, Janssen, Pfzer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Galapagos, Nycomed, Boeringher, Takeda, Zydus, Epirus and Eli Lilly and Co. JMK is a consultant and shareholder of Corrona, LLC, and a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Gilead, GlaxoSmithKline, Eli Lilly and Co., Pfizer, Regeneron and Sanofi.

  • Patient consent for publication Patients were not consulted regarding the design of the studies.

  • Ethics approval All trials were conducted in accordance with the ethical principles of Declaration of Helsinki and Good Clinical Practice guidelines. The institutional review board at each investigational centre approved the study protocols. All patients provided written informed consent.

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

  • Data availability Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data availabilty agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data availabilty environment. For details on submitting a request, see the instructions provided at www.vivli.org.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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