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Article Dans Une Revue British Journal of Dermatology Année : 2023

Major adverse cardiovascular events in patients treated with oral Janus kinase inhibitors for atopic dermatitis: a systematic review and meta-analysis

Résumé

BACKGROUND: On the basis of safety data on patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors has been linked to the occurrence of major adverse cardiovascular events (MACEs). However, these inflammatory diseases are pro-atherogenic; in contrast, patients with atopic dermatitis (AD) do not usually have a high cardiovascular (CV) comorbidity burden. METHODS: We systematically searched the PubMed, Embase, Cochrane Library and Google Scholar databases from their inception to September 2nd, 2022. Cohort studies, randomized controlled trials and pooled safety analyses providing CV safety data on patients taking JAK inhibitors for AD were selected. We included patients aged 12 and over. We built a "controlled-period" cohort (9,309 patients: 6,000 exposed to JAK inhibitors and 3,309 exposed to comparators) and an "all JAK inhibitors" cohort (9,118 patients exposed to a JAK inhibitor in any of the included studies). The primary outcome was a composite of acute coronary syndrome (ACS), ischemic stroke, and CV death. The broader secondary MACE outcome encompassed ACS, stroke (whether ischemic or hemorrhagic), transient ischemic attack, and CV death. The frequency of primary and secondary MACEs was assessed in both cohorts. A fixed-effects meta-analysis using Peto’s method was used to calculate the odds ratio (OR) [95% confidence interval (CI)] for MACEs in the "controlled-period" cohort. Risk of bias evaluation was made using the Cochrane Risk of bias tool version 2. Certainty of evidence used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Eight percent of the initially identified records met the selection criteria, corresponding to 23 records included in the "all JAK inhibitors" cohort". The patients had been exposed to baricitinib, upadacitinib, abrocitinib, ivarmacitinib, placebo or dupilumab. Four primary events (3 with JAK inhibitors and 1 with placebo) and 5 secondary events (4 with JAK inhibitors and 1 with placebo) occurred among 9,309 patients in the "controlled-period" cohort (MACE frequency = 0.04 % and 0.05%, respectively). Eight primary events and 13 secondary events occurred among 9,118 patients in the "all JAK inhibitors" cohort (MACE frequency = 0.08 and 0.14 %, respectively). Odds ratio for primary MACEs in patients with AD treated with JAK inhibitors compared to placebo or dupilumab was 1.35 (95% CI 0.15-12.21; I2, 12%, very low certainty of evidence). CONCLUSION: Our review highlighted rare cases of MACE among JAK inhibitors users for AD. Janus kinase inhibitors may have little to no effect on the occurrence of MACEs in patients with AD compared to comparators but the evidence is very uncertain. Real-life, long-term, population-level safety studies are needed.
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Dates et versions

hal-04164959 , version 1 (18-07-2023)

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Cécile Ertus, Lucie-Marie Scailteux, Alain Lescoat, Pauline Berthe, Vincent Auffret, et al.. Major adverse cardiovascular events in patients treated with oral Janus kinase inhibitors for atopic dermatitis: a systematic review and meta-analysis. British Journal of Dermatology, 2023, ⟨10.1093/bjd/ljad229⟩. ⟨hal-04164959⟩
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