Related Experiment Video
Updated: May 21, 2025
Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Major Adverse Cardiovascular Events Related to JAK Inhibitors: A Disproportionality Analysis Using the WHO Global
Raffaella Di Napoli1,2,3, Christophe Richez4,5, Cristina Scavone6,7,8
1Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138, Naples, Italy. raffaella.dinapoli@unicampania.it.
Insights
Janus kinase inhibitors (JAKis) show a higher reporting frequency for major adverse cardiac events (MACE), particularly stroke, compared to anti-tumor necrosis factor-α (anti-TNFα) drugs in rheumatoid arthritis patients.
Area of Science:
- Rheumatology
- Cardiovascular Safety
- Pharmacovigilance
Background:
- Rheumatoid arthritis (RA) treatments like Janus kinase inhibitors (JAKis) and anti-tumor necrosis factor-α (anti-TNFα) have unclear cardiovascular safety profiles.
- Understanding the comparative cardiovascular risk of these RA therapies is crucial for patient management.
Purpose of the Study:
- To analyze individual case safety reports of major adverse cardiac events (MACE) and stroke.
- To compare the frequency of cardiovascular event reporting between JAKis and anti-TNFα in RA patients.
Main Methods:
- Utilized the WHO VigiBase® database for a case/non-case study analysis.
- Calculated time to onset (TTO) for MACE and employed reporting odds ratios (ROR) to assess event frequencies.
- Descriptive analysis identified trends in MACE reporting associated with JAKis versus anti-TNFα.
Main Results:
- Identified 18,099 MACE cases; 14% were linked to JAKis, predominantly in women and older adults (≥65 years).
- JAKis showed a shorter median time to MACE onset (210 days) compared to anti-TNFα (690 days).
- JAKis had higher odds of MACE reporting (ROR 1.38), driven by non-fatal stroke (ROR 1.65), with increased risk also noted in younger patients (<65 years).
Conclusions:
- JAKis are associated with a higher reporting frequency of MACE, especially stroke, and a shorter onset time compared to anti-TNFα in RA.
- Findings suggest distinct cardiovascular safety profiles between JAKis and anti-TNFα, supporting preference for anti-TNFα in at-risk RA patients.
- Further research is warranted to confirm these findings and guide clinical decision-making for RA patients with cardiovascular risk factors.
Background:
Rheumatoid arthritis (RA) is commonly treated with Janus kinase inhibitors (JAKis) and anti-tumor necrosis factor-α (anti-TNFα), but the cardiovascular safety profiles of these drugs remain unclear.
Objective:
The aim of this study was to describe the individual case safety reports of major adverse cardiac events (MACE) or stroke and to determine whether there was a difference in the frequency of reporting of cardiovascular events between JAKis and anti-TNFα used in RA.
Methods:
A case/non-case study was conducted using the WHO VigiBase® database. Descriptive analysis was performed, the time to onset (TTO) of MACE was calculated, and the reporting odds ratio (ROR) was used to estimate the frequency of MACE reports associated with JAKis versus anti-TNFα in RA.
Results:
A total of 18,099 cases of MACE were identified, of which 2543 (14%) were associated with JAKis, predominantly in women (65.4%) and in patients aged ≥65 years (49.9%). The median time to onset was 210 days (IQR 60-510) for JAKis and 690 days (210-1460) for anti-TNFα. JAKis were associated with higher odds of reporting MACE (ROR 1.38 [95% CI 1.32-1.44]), mainly due to non-fatal stroke (1.65 [1.55-1.75]). Stroke as a whole showed similar results (1.62 [1.53-1.72]). The ROR of MACE was also slightly increased in patients aged <65 years treated with JAKis (1.29 [1.21-1.39]).
Conclusions:
Compared with anti-TNFα, JAKis were more associated with MACE, especially stroke, and with a shorter time to onset. These data support the hypothesis of a different cardiovascular reporting frequency between JAKis and anti-TNFα. In patients with identified cardiovascular risk, anti-TNFα should be preferred to JAKis until more definitive results are available.
More Related Videos
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:19Pharmacovigilance
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
01:20The JAK-STAT Signaling Pathway
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors