Role of Tumor Necrosis Factor-α Inhibitors in the Treatment and Occurrence of Acne A Systematic Review

Importance Tumor necrosis factor-alpha inhibitors (TNFis) approved to treat several inflammatory diseases are sometimes used off label to treat severe forms of acne that are refractory to conventional therapies. However, use of TNFis can also be followed by acne occurrence, suggesting an association between TNFis and acne. Most of the literature on the topic comprises case reports and series that have not been reviewed in a systematic manner. Objective To characterize the demographic characteristics, clinical presentations, treatments, and outcomes of patients receiving TNFis to treat acne and patients who develop acne following treatment of other conditions with TNFis. Evidence Review A systematic literature review was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. PubMed and Web of Science were searched from inception through October 17, 2022. Included studies reported on patients of any sex or age who received TNFis whose treatment was followed by resolution or occurrence of acne. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. Findings A total of 53 studies reporting on 64 patients who received TNFis for the treatment of acne (n = 47) or who experienced acne after treatment with TNFis for a different condition (n = 17) (mean age, 28.7 years; range, 12-64 years; 6 female individuals [8.8%]) were included. The TNFis used included adalimumab, infliximab, and etanercept. Among the 47 patients treated for acne with TNFis, most had previously received antibiotics (31 [66.0%]) or isotretinoin (32 [68.1%]). Most (44 [93.6%]) experienced partial improvement (25 [53.2%]) or clearance (19 [40.4%]) with very few adverse effects reported (3 [6.4%]). Acne manifested as part of an inflammatory syndrome for 30 patients (63.8%). Among the 17 patients treated TNFis for a different condition followed by the occurrence of acne, only 1 patient (5.9%) reported having a history of acne. Therapy with TNFis was either discontinued (8 [47.1%]) or altered (6 [35.3%]) in most patients due to acne occurrence, typically with improvement in symptoms. Conclusions and Relevance The results of this systematic review suggest that TNFis can be effective in treating refractory acne but can also be associated with the occurrence of acne in certain instances. Further studies elucidating the role that TNF plays in treating and inducing acne could yield insight into off-label TNFi use and acne pathogenesis, potentially guiding clinical care of patients with acne treated or induced by TNFis.