Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis

Peter C. Taylor, Michael E. Weinblatt, Gerd R. Burmester, Terence P. Rooney, Sarah Witt, Chad D. Walls, Maher Issa, Claudia A. Salinas, Chadi Saifan, Xin Zhang, Anabela Cardoso, Miguel A. González-Gay, Tsutomu Takeuchi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately-to-severely active rheumatoid arthritis (RA). Methods: Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long-term extension study. The data analysis set designated “All-bari-RA” included all baricitinib exposures at any dose. Results: Overall, 3,492 RA patients received baricitinib (7,860 patient-years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient-years for placebo and 0.8 per 100 patient-years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient-years for placebo and 0.5 per 100 patient-years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient-years for placebo and 2.4 per 100 patient-years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo-controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg–4 mg-extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient-years in those receiving 2 mg baricitinib and 0.6 per 100 patient-years in those receiving 4 mg baricitinib). In the All-bari-RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient-years. Conclusion: In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer-term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA.

Original languageEnglish
Pages (from-to)1042-1055
Number of pages14
JournalArthritis and Rheumatology
Volume71
Issue number7
DOIs
Publication statusPublished - 2019 Jul 1

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Rheumatoid Arthritis
Safety
Pulmonary Embolism
Venous Thrombosis
Incidence
Placebos
Therapeutics
baricitinib
Heart Failure
Clinical Trials

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Taylor, P. C., Weinblatt, M. E., Burmester, G. R., Rooney, T. P., Witt, S., Walls, C. D., ... Takeuchi, T. (2019). Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis. Arthritis and Rheumatology, 71(7), 1042-1055. https://doi.org/10.1002/art.40841

Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis. / Taylor, Peter C.; Weinblatt, Michael E.; Burmester, Gerd R.; Rooney, Terence P.; Witt, Sarah; Walls, Chad D.; Issa, Maher; Salinas, Claudia A.; Saifan, Chadi; Zhang, Xin; Cardoso, Anabela; González-Gay, Miguel A.; Takeuchi, Tsutomu.

In: Arthritis and Rheumatology, Vol. 71, No. 7, 01.07.2019, p. 1042-1055.

Research output: Contribution to journalArticle

Taylor, PC, Weinblatt, ME, Burmester, GR, Rooney, TP, Witt, S, Walls, CD, Issa, M, Salinas, CA, Saifan, C, Zhang, X, Cardoso, A, González-Gay, MA & Takeuchi, T 2019, 'Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis', Arthritis and Rheumatology, vol. 71, no. 7, pp. 1042-1055. https://doi.org/10.1002/art.40841
Taylor PC, Weinblatt ME, Burmester GR, Rooney TP, Witt S, Walls CD et al. Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis. Arthritis and Rheumatology. 2019 Jul 1;71(7):1042-1055. https://doi.org/10.1002/art.40841
Taylor, Peter C. ; Weinblatt, Michael E. ; Burmester, Gerd R. ; Rooney, Terence P. ; Witt, Sarah ; Walls, Chad D. ; Issa, Maher ; Salinas, Claudia A. ; Saifan, Chadi ; Zhang, Xin ; Cardoso, Anabela ; González-Gay, Miguel A. ; Takeuchi, Tsutomu. / Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis. In: Arthritis and Rheumatology. 2019 ; Vol. 71, No. 7. pp. 1042-1055.
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abstract = "Objective: To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately-to-severely active rheumatoid arthritis (RA). Methods: Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long-term extension study. The data analysis set designated “All-bari-RA” included all baricitinib exposures at any dose. Results: Overall, 3,492 RA patients received baricitinib (7,860 patient-years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient-years for placebo and 0.8 per 100 patient-years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient-years for placebo and 0.5 per 100 patient-years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient-years for placebo and 2.4 per 100 patient-years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo-controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg–4 mg-extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient-years in those receiving 2 mg baricitinib and 0.6 per 100 patient-years in those receiving 4 mg baricitinib). In the All-bari-RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient-years. Conclusion: In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer-term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA.",
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AU - Witt, Sarah

AU - Walls, Chad D.

AU - Issa, Maher

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