Diagnosis of AD, use of JAK inhibitors did not show increased risk of venous thromboembolism
According to this new meta-analysis, patients with atopic dermatitis (AD) did not have an increased risk of venous thromboembolism, independent of the use of Janus kinase inhibitors.
According to the results of the study published in JAMA Dermatology.
Approved for the treatment of AD, JAK inhibitors have shown favorable clinical results in previous research. However, black box warnings issued by the FDA about an increased risk of blood clots after taking tofacitinib, baricitinib and upadacitinib to treat arthritis and other chronic inflammatory conditions have raised concerns among patients with MA regarding the risk of VTE, a life-threatening disease. associated with high recurrence and mortality rates.
“Although JAK inhibitors have been approved for the treatment of AD in recent years, to our knowledge, there has been no systematic assessment of the risk of VTE in patients with AD and the profile of JAK inhibitors in the treatment of AD,” the study authors said. .
They conducted a systematic review and meta-analysis to assess the current evidence on the association of AD with incident VTE, including deep vein thrombosis and pulmonary embolism, and risk of incident VTE in AD patients receiving JAK inhibitors.
Studies registered in MEDLINE, Embase, Cochrane Library and Web of Science up to February 5, 2022 were considered for meta-analysis based on certain exclusion criteria:
- Phase 2 and Phase 3 randomized clinical trials (RCTs) investigating the safety of JAK inhibitors for patients with AD
- An intervention group comprising participants with AD receiving treatment with JAK inhibitors and a control group comprising participants with AD receiving placebo or dupilumab
- Reporting of the number of VTE events
- Studies with patients using topical JAK inhibitors (eg, delgocitinib, ruxolitinib, and tofacitinib) were excluded
“The PRISMA directive (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) has been followed. The risk of bias of the included cohort studies and RCTs was assessed by the Newcastle-Ottawa scale and the Cochrane risk of bias tool 2, respectively,” explained the study authors. “A random-effects model meta-analysis was conducted to calculate the combined HR and risk difference for the VTE incident.”
The meta-analysis included 2 cohort studies and 15 RCTs including 466,993 patients, indicating that only 0.7% of the initially identified studies fulfilled the selection criteria. Four JAK inhibitors (abrocitinib, baricitinib, upadacitinib and SHR0302) were studied.
Meta-analysis results showed no significant association between Alzheimer’s disease and incident VTE (pooled RR, 0.95; 95% CI, 0.62-1.45; heterogeneity [I2] = 92%), with an overall reported VTE incidence rate of 0.23 events per 100 patient-years.
Three of 5722 AD patients (0.05%) receiving treatment with JAK inhibitors experienced VTE, compared to 1 of 3065 AD patients (0.03%) receiving placebo or dupilumab (Mantel-Haenszel risk difference, 0; 95% CI, 0-0; I2 = 0%).
The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in AD participants receiving JAK inhibitors and placebo, respectively, with no VTE events recorded in the trials comparing JAK inhibitors to dupilumab. The results were similar for the 4 unique JAK inhibitors studied.
Since the included studies were mostly conducted in Western countries, the researchers said the results may not be generalizable. Other limitations cited were the presence of statistical heterogeneity on the association between AD and VTE in the meta-analysis, unknown VTE risk based on different models of AD (eg, persistent, recurrent forms or appearing in adulthood) and the lack of data on rare or long-term adverse events, such as VTE.
“These results may provide a baseline for clinicians in prescribing JAK inhibitors for patients with AD. Additional evidence from real-world, longer-term safety data is warranted,” the researchers concluded.
Chen TL, Lee LL, Huang HK, et al. Association of the risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: a systematic review and meta-analysis. JAMA Dermatol. Published online August 24, 2022. doi:10.1001/jamadermatol.2022.3516