What is the cancer risk associated with taking Ritlecitinib (JAK inhibitor)?

Cancer Risk Associated with Ritlecitinib (JAK Inhibitor)

JAK inhibitors may be associated with a higher risk of cancer than TNF antagonists, particularly in older adults with cardiovascular risk factors such as smoking or prior cardiovascular disease. 1

Overview of Ritlecitinib and Cancer Risk

Ritlecitinib is a selective JAK3/TEC family kinase inhibitor that has been studied primarily for alopecia areata and other immune-mediated inflammatory diseases. Understanding its cancer risk profile is important for clinical decision-making.

Current Evidence on Ritlecitinib-Specific Cancer Risk

The most recent and comprehensive safety data for ritlecitinib comes from the ALLEGRO clinical trial program:

• In the all-exposure cohort (n=1294) with median exposure of 624 days (2091.7 patient-years):
  • Malignancy rate (excluding nonmelanoma skin cancer): 0.5% (0.3/100 patient-years) 2
  • No concerning cancer signal was identified in this study population

JAK Inhibitor Class Cancer Risk

Multiple guidelines highlight cancer risk as a concern with JAK inhibitors:

• Expert consensus statements note that "rates of malignancy may be higher with JAK inhibition compared with those with TNF inhibitors" 1
• JAK inhibitors including abrocitinib, baricitinib, tofacitinib, and upadacitinib carry boxed warnings for increased malignancy risk 1
• The risk appears to be higher in:
  • Patients over 65 years of age 1, 3
  • Current or previous long-term smokers 1
  • Those with a history of cardiovascular disease 1
  • Those with a history of prior cancer 1

Risk Assessment and Monitoring

When considering ritlecitinib therapy, the following approach is recommended:

1. Pre-treatment assessment:

   • Evaluate for history of malignancy
   • Assess cardiovascular risk factors (age >65, smoking history, prior cardiovascular disease)
   • Consider alternative therapies in high-risk patients

2. During treatment:

   • Regular skin examinations for early detection of skin cancers
   • Age-appropriate cancer screening according to standard guidelines
   • Monitor for new or unusual symptoms that could indicate malignancy

Risk in Context

The absolute cancer risk with ritlecitinib appears to be low based on current data:

• In the ALLEGRO program, the malignancy rate was 0.3/100 patient-years 2
• Patient preference studies indicate that patients with alopecia areata are willing to accept a mean increase of 1.63 absolute percentage points in 3-year cancer risk for the benefits of treatment 4

Practical Recommendations

1. For lower-risk patients (younger, no history of cancer, no cardiovascular risk factors):

   • Ritlecitinib can be considered with appropriate monitoring
   • Regular skin examinations and age-appropriate cancer screening

2. For higher-risk patients (older adults, history of cancer, smokers, cardiovascular disease):

   • Consider alternative therapies with potentially lower malignancy risk
   • If ritlecitinib is necessary, implement more frequent monitoring
   • Counsel on smoking cessation if applicable

Conclusion

While JAK inhibitors as a class carry warnings about increased cancer risk, the specific data for ritlecitinib from clinical trials shows a relatively low malignancy rate (0.3/100 patient-years). However, caution is warranted, particularly in older patients and those with cardiovascular risk factors or a history of cancer. The decision to use ritlecitinib should balance its efficacy against the potential cancer risk in each individual case.