Long-term adverse event risks of oral JAK inhibitors versus immunomodulators: a literature review

The long-term adverse event risks associated with oral Janus kinase (JAK) inhibitors compared to broader immunomodulators are poorly understood, with limited comparative studies available. This study aims to assess the long-term adverse event risks of oral JAK inhibitors compared to broader immunomodulators in dermatology. A PubMed search included terms such as specific drug names and “adverse events,” “long-term safety,” “malignancy,” “cardiovascular events,” and/or “infections.” Included were studies with over one year of medication exposure reporting adverse events. A total of 25 studies were included, comprising 19 clinical trials and 6 cohort studies, representing greater than 100,000 patient years of data. We found comparable long-term incidence rates of malignancy (excluding non-melanoma skin cancer (NMSC)), venous thromboembolism (VTE), and serious infections between oral JAK inhibitors and broader immunomodulators. Oral JAK inhibitors demonstrated lower incidence rates of NMSC and major adverse cardiovascular events (MACE), but higher rates of herpes zoster virus (HZV) infections compared to non-JAK medications. Study limitations include variations in underlying diseases, age, and comorbidities between studies introducing patient population heterogeneity. Overall, oral JAK inhibitors may be viable long-term treatment options given their comparable safety profile to broader immunomodulators currently used in dermatology. However, monitoring for HZV infections may be warranted. These findings aid clinicians in making informed treatment decisions and prioritizing patient safety.