JAK Inhibitors in Atopic Dermatitis: No Increased Risk of Clots

Do patients with other conditions besides rheumatoid arthritis have an increased risk of blood clots (venous thromboembolism) with JAK inhibitors?

The ORAL Surveillance trial created concern that JAK inhibitors may be associated with side effects such as cancer, heart disease, blood clots (venous thromboembolism) and infections. These were studies done in patients 50 years and over with rheumatoid arthritis who had risk factors for cardiovascular disease.

This led to a blanket warning from the FDA for all JAK inhibitors that use of these medications could potentially increase the risk of blood clots (venous thromboembolism) , heart disease, infections and cancer.

It’s not clear if other patient populations besides rheumatoid arthritis are likely to have an increased risk of venous thromboembolism . Clearly this is important as we come to understand whether our hair loss patients are at risk for certain side effects if they start JAK inhibitors.

Only one trial in hair loss patients has been large enough to get some information about the risk of venous thromboembolism. The BRAVE AA 1 and BRAVE AA 2 trials were randomized studies of baricitinib against placebo. These studies did not show an increase risk of venous thromboembolism . We are awaiting other good trials in the hair world.

 Chen T-L et al, 2022

Authors of a new study set out to evaluate the risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD) receiving treatment with Janus kinase (JAK) inhibitors.

In order to do so,  MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched. Cohort studies examining the association of AD with incident VTE and randomized clinical trials (RCTs) reporting VTE events in participants with AD receiving JAK inhibitors were included.

Two cohort studies and 15 RCTs with a total of 466 993 participants were included in the calculations. Overall, the meta-analysis found no significant association of AD with incident VTE (HR, 0.95; 95% CI 0.62-1.45). The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in participants with AD receiving JAK inhibitors and placebo, respectively. The findings were similar in 4 unique JAK inhibitors (abrocitinib, baricitinib, upadacitinib, and a JAK inhibitor known as SHR0302).

 Conclusion and Summary

Overall, the results here  suggest that the currently available evidence does not detect an increased risk of VTE associated with AD or treatment with JAK inhibitors.  

This is important as it reminds us that specific patient populations will be important to study as we go about understanding the true risk with JAK inhibitors. If we want to know if JAK inhibitors cause blood clots in patients with alopecia areata, we’ll need to study patients with alopecia areata and not rely on data from patients with rheumatoid arthritis or atopic dermatitis. If we want to know if JAK inhibitors cause blood clots in patients with frontal fibrosing alopecia, we’ll need to study patients with frontal fibrosing alopecia and not rely on data from patients with rheumatoid arthritis or atopic dermatitis or alopecia areata.

A recent review by Misra et al offered the opinion that the risk of blood clots may even differ among JAK inhibitors and tofacitinib could potentially have different risk than baricitinib and upadacitinib. Misra and colleagues even went so far in their review as to say “Based on the available literature from trials and long-term follow-up studies of baricitinib and upadacitinib, there exists insufficient evidence to extend the warning of MACE/ VTE with tofacitinib to these drugs.“

The next few years will be very important to understand not only the class effect of these drugs but also how they different in patients with different medical conditions.

REFERENCE

Chen T-L et al. Association of Risk of Incident Venous Thromboembolism With Atopic Dermatitis and Treatment With Janus Kinase Inhibitors: A Systematic Review and Meta-analysis. JAMA Dermatol. 2022 Aug 24;e223516.

Misra D et al. Cardiovascular risks associated with Janus kinase inhibitors: peering outside the black box. Clin Rheumatol. 2022 Oct 20.