Atopic dermatitis (AD) is not associated with an increased risk for venous thromboembolism events, and neither are JAK inhibitors when used to treat AD, according to data from a systematic review and meta-analysis published in JAMA Dermatology.
Investigators conducted a comprehensive literature search on electronic databases for cohort studies analyzing the association of AD with incident venous thromboembolism (VTE) that reported the risk estimates of incident VTE. Both deep vein thrombosis (DVT) and pulmonary embolism (PE) were considered VTE events.
To further examine the risk for VTE in patients with AD treated with JAK inhibitors, investigators included phase 2 and 3 randomized clinical trials analyzing the safety of JAK inhibitors in patients with AD that reported the number of VTE events. They excluded open-label or long-term extension studies without a control arm and those using topical JAK inhibitors. Investigators conducted 2 separate meta-analyses: 1 for cohort studies on the association of AD and incident VTE and 1 for RCTs on the risk for incident VTE inpatients with AD on JAK inhibitors. Pooled hazard ratios (HRs) and corresponding confidence intervals were synthesized to determine the association between AD and incident VTE, and absolute risk differences were used to measure the risk for incident VTE in patients with AD treated with JAK inhibitors.
There were 2 cohort studies and 15 randomized clinical trials included in the final analysis, encompassing 466,993 participants. The cohort studies were both conducted in the United States and were considered high quality according to the Newcastle-Ottawa Scale. The randomized clinical trials were conducted in multiple countries and 5 of them had concerns of bias. Most participants were young and middle-aged adults, except for 1 study which mainly included adolescents. There were 4 JAK inhibitors investigated: abrocitinib, baricitinib, upadacitinib, and SHR0302.
The crude incidence rate of VTE among patients with AD was 0.24 and 0.18 events per 100 patient-years. The risk for incident VTE did not significantly increase among AD patients compared to control participants (pooled HR, 0.95; 95% CI, 0.62-1.45). The overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years.
There were 3 of 5722 (0.05%) patients with AD treated with JAK inhibitors who experienced VTE events compared with 1 of 3065 (0.03%) treated with placebo or dupulimab. The meta-analysis found no significant difference in the risk for VTE incidence between patients treated with any of the 4 JAK inhibitors and patients treated with placebo or dupilumab. The overall incidence rate of VTE was 0.15 events per 100 patient-years among those treated with JAK inhibitors and 0.12 events per 100 patient-years among those treated with placebo.
The study was limited by the small number of cohort studies, and the RCTS may have been underpowered or of too-short duration to identify long-term adverse events, such as VTE.
“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” the study authors wrote, also noting that “further evidence from real-world data on longer-term safety are warranted.”
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. August 24, 2022. doi:10.1001/jamadermatol.2022.3516