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Cardiovascular safety, cancer and Jak-inhibitors: Differences to be highlighted

Maurizio Benucci1, Arianna Damiani2, Maria Infantino3

  • 1Rheumatology Unit, S.Giovanni di Dio Hospital, Azienda USL-Toscana Centro Florence, Italy.

Pharmacological Research
|July 30, 2022
PubMed

Insights

Janus kinase inhibitors (JAKis) show increased risks of major adverse cardiovascular events and cancer in rheumatoid arthritis patients. Further research is needed to evaluate the safety profiles of different JAK inhibitors.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Immunology

Background:

  • Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular and malignancy risks.
  • Janus kinase inhibitors (JAKis) are targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) that modulate inflammatory signaling pathways.
  • Concerns exist regarding the cardiovascular and neoplastic risks associated with JAK inhibitors in RA patients.

Purpose of the Study:

  • To review existing literature on the cardiovascular and neoplastic risks of JAK inhibitors in rheumatoid arthritis.
  • To evaluate the safety profiles of different JAK inhibitors based on their selectivity for JAK family members (JAK1, JAK2, JAK3, Tyk2).

Main Methods:

  • Literature review of randomized controlled trials (RCTs) and real-world registries.
  • Analysis of data regarding major adverse cardiovascular events (MACE) and cancer risk.
  • Comparison of safety profiles among different JAK inhibitors.

Main Results:

  • A recent RCT indicated increased risks of MACE (HR 1.33) and cancer (HR 1.49) with tofacitinib over 4 years.
  • FDA has issued class warnings for tofacitinib, baricitinib, and upadacitinib.
  • Conflicting data exists between RCTs and real-world registries regarding JAK inhibitor safety.

Conclusions:

  • The varying selectivity of JAK inhibitors for JAK family members may influence their efficacy and safety.
  • Further evaluation is necessary to understand the specific cardiovascular and neoplastic risks associated with each JAK inhibitor.
  • Clarifying the safety profile of JAK inhibitors is crucial for managing rheumatoid arthritis patients.
Keywords:
BaricitinibCancerCardiovascular eventsFilgotinibTofacitinibUpadacitinib

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