Anti-JAKs safe in skin conditions

3 minute read


The drugs don’t increase the risk of MACE or blood clots for dermatology patients, research suggests.


Janus kinase (JAK) inhibitors are safe for people with immune-mediated inflammatory skin diseases – at least in the short-term, researchers say. 

A systematic review and meta-analysis of 35 randomised clinical trials found no significant difference in the number of major cardiovascular events, all-cause mortality or venous thromboembolism when comparing JAK inhibitors and placebo or active comparator after an average follow-up of five months. 

The JAMA Dermatology study findings are in contrast to a study involving rheumatoid arthritis patients, published last year, that found higher rates of major adverse events in those who took the JAK inhibitor tofacitinib. 

In the latest study, the US researchers included more than 20,000 patients with dermatologic conditions such as atopic dermatitis, alopecia areata, psoriasis (including psoriatic arthritis) and vitiligo. 

Just over half the patients were male, and the average age was 38. 

The analysis included the drugs tofacitinib, abrocitinib, baricitinib, upadacitinib, ritlecitinib, delgocitinib cream and ruxolitinib cream. 

The researchers said it was the first study to analyse these risks when JAK inhibitors were used for dermatologic indications.  

But they said it was unclear whether the previously raised risks of JAK inhibitors in rheumatology patients were due to patient-level cardiovascular risk factors or the drugs themselves. 

For that reason, it was best to be cautious about which patients to treat with JAK inhibitors and to monitor them closely, they said. 

“Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. 

“Cardiovascular risk assessment should continue for the duration of treatment.”  

Concerns about JAK inhibitors were raised when the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study found that patients with rheumatoid arthritis who took tofacitinib 10mg over four years had an increased risk of major adverse cardiovascular events, venous thromboembolism, serious infections, malignant neoplasm and death compared with patients who took a TNF inhibitor.  

As a result of that study, the FDA added a boxed warning label to oral and topical JAK inhibitors.  

But the JAMA Dermatology researchers pointed out that the ORAL Surveillance study included patients with at least one cardiovascular risk factor and went for four years, compared to an average of five months in their analysis.  

They also said that the patients in their review and meta-analysis were younger on average than those in the ORAL Surveillance study (a mean age of 38 compared with 61).  

Therefore, the incidence of major adverse cardiovascular events, venous thromboembolism and all-cause mortality in their study would be low, “and has limited generalisability in an older patient population”, they said. 

“Also, the majority of JAK inhibitors tested in dermatology clinical trials are selective for JAK1/2, which differs from the selectivity of tofacitinib, which predominantly inhibits JAK1/3.  

“Finally, the control group in ORAL Surveillance consisted of patients with RA receiving tumour necrosis factor inhibitors.” 

JAMA Dermatology 2023, online 1 November 

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