Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies

Rheumatology (Oxford). 2017 Jan;56(1):46-57. doi: 10.1093/rheumatology/kew329. Epub 2016 Oct 22.

Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality.

Methods: Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration. Disease activity markers included CRP and ESR. Fatigue and vitality were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Short Form Health Survey-36 vitality domain scores.

Results: In phase 3 studies, mean neutrophil and lymphocyte counts decreased and mean haemoglobin levels increased in all tofacitinib treatment groups. Haemoglobin levels and neutrophil counts stabilized in the LTE studies, while lymphocyte count decreases stabilized at approximately month 48. Increased haemoglobin was associated with decreased ESR and CRP levels. Clinically meaningful reductions in haemoglobin levels (⩾3 g/dl from baseline or haemoglobin ⩽7 g/dl) occurred in <1.0% of patients in all treatment groups. FACIT-F and Short Form Health Survey-36 vitality scores were weakly correlated with haemoglobin levels.

Conclusion: Small changes in haematological parameters were seen with tofacitinib treatment, which stabilized over time in the LTE studies. Changes in haemoglobin levels, although associated with changes in ESR and CRP, were not associated with fatigue or vitality.

Keywords: anaemia; disease activity; fatigue; haemoglobin; lymphocyte; neutrophil; rheumatoid arthritis; tofacitinib; vitality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Cell Count
  • Clinical Trials, Phase III as Topic
  • Fatigue / etiology
  • Fatigue / physiopathology
  • Female
  • Hemoglobins / metabolism*
  • Humans
  • Longitudinal Studies
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neutrophils / cytology*
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Hemoglobins
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • C-Reactive Protein