Changes in selected haematological parameters associated with JAK1/JAK2 inhibition observed in patients with rheumatoid arthritis treated with baricitinib.

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 (-1.36×10 ⁹ /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 (+0.30×10 ⁹ /L) within 1 month, then decreased to baseline (weeks 12-24). Mean platelet counts increased at week 2 (+51×10 ⁹ /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.
Competing Interests: 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.
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