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

Abstract

ObjectiveTo characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.MethodsData 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).ResultsMean 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).ConclusionsModerate 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.

Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database

“…Changes in selected haematological parameters following once-daily baricitinib dose were previously disclosed. 16 The IR for laboratory-related treatment-emergent events included anaemia (1.74, 95% CI 1.53 to 1.97), neutropaenia (0.4, 95% CI 0.31 to 0.52), lymphopaenia (1.04, 95% CI 0.89 to 1.22) and thrombocytosis (0.3, 95% CI 0.24 to 0.43).…”

“…Patients with RA are at an increased risk of DVT and PE (IR 0.3–0.8/100 patient-years) 16 compared with the general population. 37 38 In this analysis, the IR of DVT/PE in patients treated with baricitinib was consistent with previously reported data 6 39 and comparable with other JAK inhibitors.…”

Transient leukocytopenia following combination therapy for COVID-19

“…Since changes in leukocyte count occurred during the combination therapy, drug-induced effects may have resulted in the leukocytopenia. Considering the mechanism of action of baricitinib [ 7 ], it is a potential candidate for inducing transient leukocytopenia. Interactions between baricitinib and remdesivir may have affected transient leukocytopenia.…”

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

“…In addition, there are currently approximately 80 clinical trials testing the safety and efficacy of Baricitinib in other autoimmune diseases and in SARS-CoV-2patients. The primary AEs of Baricitinib include opportunistic infections, such as herpes zoster, gastro-intestinal (GI) side effects, changes in hematological parameters, malignancy and venous thromboembolism [151][152][153]. No studies have been conducted regarding the efficacy of Baricitinib in solid tumors.…”