Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment

Josef S. Smolen, Mark C. Genovese, Tsutomu Takeuchi, David L. Hyslop, William L. Macias, Terence Rooney, Lei Chen, Christina L. Dickson, Jennifer Riddle Camp, Tracy E. Cardillo, Taeko Ishii, Kevin L. Winthrop

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). We evaluated baricitinib's safety profile through 288 weeks (up to September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1 longterm extension (LTE)]. Methods. The “all-bari-RA” group included patients who received any baricitinib dose. Placebo comparison was based on the 6 studies with 4 mg and placebo up to Week 24 (“placebo-4 mg” dataset). Dose response assessment was based on 4 studies with 2 mg and 4 mg including LTE data (“2 mg-4 mg-extended”). The uncommon events description used the non-controlled all-bari-RA. Results. There were 3492 patients who received baricitinib for 6637 total patient-years (PY) of exposure (median 2.1 yrs, maximum 5.5 yrs). No differences in rates of death, adverse events leading to drug discontinuation, malignancies, major adverse cardiovascular event (MACE), or serious infections were seen for 4 mg versus placebo or for 4 mg versus 2 mg. Infections including herpes zoster were significantly more frequent for 4 mg versus placebo. Deep vein thrombosis/pulmonary embolism were reported with 4 mg but not placebo [all-bari-RA incidence rate (IR) 0.5/100 PY]; the IR did not differ between doses (0.5 vs 0.6/100 PY, 2 mg vs 4 mg, respectively) or compared to published RA rates. All-bari-RA had 6 cases of lymphoma (IR 0.09/100 PY), 3 gastrointestinal perforations (0.05/100 PY), 10 cases of tuberculosis (all in endemic areas; 0.15/100 PY), and 22 all-cause deaths (0.33/100 PY). IR for malignancies (0.8/100 PY) and MACE (0.5/100 PY) were low and did not increase with prolonged exposure. Conclusion. In this integrated analysis of patients with moderate to severe active RA with exposure up to 5.5 years, baricitinib has an acceptable safety profile in the context of demonstrated efficacy.

Original languageEnglish
Pages (from-to)7-18
Number of pages12
JournalJournal of Rheumatology
Volume46
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

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Rheumatoid Arthritis
Safety
Placebos
Therapeutics
Incidence
baricitinib
Janus Kinases
Herpes Zoster
Infection
Pulmonary Embolism
Venous Thrombosis
Cause of Death
Lymphoma
Neoplasms
Tuberculosis
Databases
Mortality

Keywords

  • Baricitinib
  • Clinical Trials
  • Janus kinase inhibitor
  • Rheumatoid arthritis
  • Safety

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. / Smolen, Josef S.; Genovese, Mark C.; Takeuchi, Tsutomu; Hyslop, David L.; Macias, William L.; Rooney, Terence; Chen, Lei; Dickson, Christina L.; Camp, Jennifer Riddle; Cardillo, Tracy E.; Ishii, Taeko; Winthrop, Kevin L.

In: Journal of Rheumatology, Vol. 46, No. 1, 01.01.2019, p. 7-18.

Research output: Contribution to journalArticle

Smolen, JS, Genovese, MC, Takeuchi, T, Hyslop, DL, Macias, WL, Rooney, T, Chen, L, Dickson, CL, Camp, JR, Cardillo, TE, Ishii, T & Winthrop, KL 2019, 'Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment', Journal of Rheumatology, vol. 46, no. 1, pp. 7-18. https://doi.org/10.3899/jrheum.171361
Smolen, Josef S. ; Genovese, Mark C. ; Takeuchi, Tsutomu ; Hyslop, David L. ; Macias, William L. ; Rooney, Terence ; Chen, Lei ; Dickson, Christina L. ; Camp, Jennifer Riddle ; Cardillo, Tracy E. ; Ishii, Taeko ; Winthrop, Kevin L. / Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. In: Journal of Rheumatology. 2019 ; Vol. 46, No. 1. pp. 7-18.
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AU - Genovese, Mark C.

AU - Takeuchi, Tsutomu

AU - Hyslop, David L.

AU - Macias, William L.

AU - Rooney, Terence

AU - Chen, Lei

AU - Dickson, Christina L.

AU - Camp, Jennifer Riddle

AU - Cardillo, Tracy E.

AU - Ishii, Taeko

AU - Winthrop, Kevin L.

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N2 - Objective. Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). We evaluated baricitinib's safety profile through 288 weeks (up to September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1 longterm extension (LTE)]. Methods. The “all-bari-RA” group included patients who received any baricitinib dose. Placebo comparison was based on the 6 studies with 4 mg and placebo up to Week 24 (“placebo-4 mg” dataset). Dose response assessment was based on 4 studies with 2 mg and 4 mg including LTE data (“2 mg-4 mg-extended”). The uncommon events description used the non-controlled all-bari-RA. Results. There were 3492 patients who received baricitinib for 6637 total patient-years (PY) of exposure (median 2.1 yrs, maximum 5.5 yrs). No differences in rates of death, adverse events leading to drug discontinuation, malignancies, major adverse cardiovascular event (MACE), or serious infections were seen for 4 mg versus placebo or for 4 mg versus 2 mg. Infections including herpes zoster were significantly more frequent for 4 mg versus placebo. Deep vein thrombosis/pulmonary embolism were reported with 4 mg but not placebo [all-bari-RA incidence rate (IR) 0.5/100 PY]; the IR did not differ between doses (0.5 vs 0.6/100 PY, 2 mg vs 4 mg, respectively) or compared to published RA rates. All-bari-RA had 6 cases of lymphoma (IR 0.09/100 PY), 3 gastrointestinal perforations (0.05/100 PY), 10 cases of tuberculosis (all in endemic areas; 0.15/100 PY), and 22 all-cause deaths (0.33/100 PY). IR for malignancies (0.8/100 PY) and MACE (0.5/100 PY) were low and did not increase with prolonged exposure. Conclusion. In this integrated analysis of patients with moderate to severe active RA with exposure up to 5.5 years, baricitinib has an acceptable safety profile in the context of demonstrated efficacy.

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