Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 May 3;12(1):7140.
doi: 10.1038/s41598-022-10777-w.

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database

Léa Hoisnard  1   2   3 , Bénédicte Lebrun-Vignes  4 , Sébastien Maury  5   6 , Matthieu Mahevas  5   7 , Khalil El Karoui  5   8   9   10 , Lydia Roy  6 , Anissa Zarour  5 , Marc Michel  5   7 , José L Cohen  5   9   10   11 , Aurélien Amiot  5   12 , Pascal Claudepierre  5   13   14 , Pierre Wolkenstein  5   13   15 , Philippe Grimbert  5   8   10 , Emilie Sbidian  5   16   13   15
Affiliations
Observational Study

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database

Léa Hoisnard et al. Sci Rep. .

Abstract

Increasing number of Janus kinase (JAK) inhibitors have been approved for chronic haematopoietic neoplasms and inflammatory/autoimmune diseases. We aimed to assess safety of the first three approved JAK inhibitors: ruxolitinib, tofacitinib and baricitinib. In this retrospective observational study, pharmacovigilance data were extracted from the World Health Organization database. Adverse events are classified according to Medical Dictionary for Regulatory Activities hierarchy. Until February 28, 2021, all Individual Case Safety Reports [ICSRs] with the suspected drug ruxolitinib, tofacitinib or baricitinib were included. Disproportionality analysis was performed and the information component (IC) was estimated. Adverse events were considered a significant signal if the lower end of the 95% credibility interval of the IC (IC025) was positive. We identified 126,815 ICSRs involving JAK inhibitors. Ruxolitinib, tofacitinib and baricitinib were associated with infectious adverse events (IC025 1.7, especially with viral [herpes and influenza], fungal, and mycobacterial infectious disorders); musculoskeletal and connective tissue disorders (IC025 1.1); embolism and thrombosis (IC025 0.4); and neoplasms (IC025 0.8, especially malignant skin neoplasms). Tofacitinib was associated with gastrointestinal perforation events (IC025 1.5). We did not find a significant increase in the reporting of major cardiovascular events. We identified significant association between adverse events and ruxolitinib, tofacinitib and baricitinib in international pharmacovigilance database.

PubMed Disclaimer

Conflict of interest statement

Aurelien Amiot received consulting fees and travel accommodations from Pfizer. Pascal Claudepierre reported receiving personal fees from Abbvie, Pfizer, Roche-Chugai Bristol-Myers Squibb, MSD, UCB, Novartis, Janssen, Lilly, Celgene. Rest of the authors do not have any competing interest to declare.

Figures

Figure 1
Figure 1
Proportion of Preferred Terms (MedDRA) with positive IC025 related to each JAK inhibitor according to the 27 different System Organ Classes. “Pregancy, puerperium and perinatal conditions” is not represented here because of no positive IC025 observed for any of the three drugs. Yellow curve represents tofacitinib, orange baricitinib and blue ruxolitinib. MedDRA: Medical Dictionary for Regulatory Activities; IC025: lower limit of the 95% credibility interval of the information component. A positive IC025 is the statistical threshold used in VigiBase.
Figure 2
Figure 2
Comparison between the three JAK inhibitors for selected adverse events. ICSR Individual Case Safety Report; ROR [95% CI] reporting odds ratio and 95% confidence interval. MedDRA Medical Dictionary for Regulatory Activities; HLT High Level Term in the MedDRA classification; HLGT High Level Group Term in the MedDRA classification; PT Preferred Term in the MedDRA classification.
See this image and copyright information in PMC

References

    1. O’Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity. 2008;28:477–487. doi: 10.1016/j.immuni.2008.03.002. - DOI - PMC - PubMed
    1. Jamilloux Y, et al. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2019;18:102390. doi: 10.1016/j.autrev.2019.102390. - DOI - PubMed
    1. You H, et al. JAK inhibitors: Prospects in connective tissue diseases. Clin. Rev. Allergy Immunol. 2020;59:334–351. doi: 10.1007/s12016-020-08786-6. - DOI - PubMed
    1. Mascarenhas J, et al. Phase II trial of Lestaurtinib, a JAK2 inhibitor, in patients with myelofibrosis. Leuk. Lymphoma. 2019;60:1343–1345. doi: 10.1080/10428194.2018.1532509. - DOI - PMC - PubMed
    1. AbbVie. A Phase 2, Long-Term Extension (LTE) Study With Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT). https://clinicaltrials.gov/ct2/show/NCT04451772 (2020).

Publication types

Substances