Janus-kinase (JAK) inhibitors do not increase the risk for venous thromboembolism (VTE) in patients being treated for atopic dermatitis (AD), according to data from a systematic review and meta-analysis published in JAMA Dermatology. No significant difference in the risk for incident VTE in participants with AD receiving JAK inhibitors and control participants with AD receiving placebo or dupilumab was found.
Investigators included cohort studies examining the association of AD with incident VTE that had an exposure group of patients with AD and a nonexposure group of people without AD and reported the risk estimates of incident VTE. To further evaluate an association with JAK inhibitors, investigators included phase 2 and 3 randomized clinical trials (RCTs) investigating the safety of JAK inhibitors for patients with AD, studies with an intervention group comprising patients with AD treated with JAK inhibitors and a control group receiving either placebo or dupilumab, and studies that reported the number of VTE events. Studies of patients using topical JAK inhibitors were excluded.
Investigators conducted 2 separate meta-analyses: 1 for cohort studies (the association of AD with incident VTE) and 1 for RCTs (the risk for incident VTE among patients with AD treated with JAK inhibitors). They synthesized pooled hazard ratios (HRs) and corresponding CIs to determine the association of AD with incident VTE, and used absolute risk differences to measure the risk for incident VTE among patients with AD treated with various JAK inhibitors.
There were 2 cohort studies and 15 RCTs included in the final analysis, with a total of 466,993 participants. The risk of incident VTE did not significantly increase among patients with AD compared to non-AD control participants (pooled HR, 0.95; 95% CI, 0.62-1.45), and the overall incidence rate of VTE among patients with AD was 0.23 events per 100 patient-years. There was also no significant difference seen in the risk for incident VTE between participants with AD receiving JAK inhibitors and control participants with AD receiving placebo or dupilumab (Mantel-Haenszel risk different, 0; 95% CI, 0-0). These findings were similar across all 4 JAK inhibitors analyzed. The overall incidence rate of VTE was 0.15 events per 100 patient-years among patients with AD treated with JAK inhibitors and 0.12 events per 100 patient-years among patients with AD treated with placebo. No VTE events comparing JAK inhibitors and dupilumab were recorded.
The study was limited by the small number of cohort studies, the statistical heterogeneity present in the meta-analysis on associations between AD and VTE, the lack of subanalyses by AD onset, and the possibly underpowered and too-short duration of the included RCTs.
Although recently published guidelines caution that AD may be associated with few cardiac comorbidities, the study authors concluded that the results of this systematic review and meta-analysis suggest that “evidence from cohort studies does not detect an increased risk of incident VTE among patients with AD, nor does the evidence from RCTs detect significant differences in the risk of incident VTE between patients with AD who were receiving treatment with JAK inhibitors and controls receiving placebo or dupilumab.”
Chen TL, Lee LL, Huang HK, Chen LY, Loh CH, Chi CC. 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;158(11):1254-1261. doi:10.1001/jamadermatol.2022.3516