Recent research emphasizes the need for healthcare providers to address patient fears regarding the safety of Janus kinase (JAK) inhibitors through clear communication and education. The study, led by Anthony J. Teixeira from the Wake Forest University School of Medicine Center for Dermatology Research, highlights strategies for managing patient concerns based on safety data and treatment considerations.
Addressing Safety Concerns
The investigators reviewed multiple studies to identify methods for addressing patient concerns about JAK inhibitors. They noted that these inhibitors offer an alternative for patients who have not responded to biologic therapies and are suitable for those without high risk of severe infections or thromboembolism.
Key Findings from Clinical Trials
One study cited was the Oral Surveillance (ORALSURV) trial, a phase 3b-4 study comparing tofacitinib to TNF inhibitors in rheumatoid arthritis (RA) patients. While the study indicated higher rates of major adverse cardiovascular events (MACE) with tofacitinib, the increase was not statistically significant. The trial also reported on venous thromboembolism (VTE), with rates of 1.2% and 2.3% in the 5-mg and 10-mg tofacitinib cohorts, respectively, compared to 0.7% in the TNF inhibitor cohort. Serious adverse events were observed in 24.1% and 26.8% of patients on 5-mg and 10-mg tofacitinib, respectively, versus 21.1% in the TNF cohort.
Safety in Dermatologic Indications
The research team found that JAK inhibitors appear to have fewer safety concerns in dermatologic applications, especially in younger patients without comorbidities. For example, the second-generation JAK1 inhibitor abrocitinib, approved for atopic dermatitis, has demonstrated minimal long-term risk of VTE, MACE, or non-melanoma skin cancer (NMSC) in clinical studies. A 12-week phase 3 study of abrocitinib showed no cardiovascular events, VTE, or cancer cases, with serious adverse events comparable to placebo.
Additional Adverse Effects
Common adverse effects associated with dermatologic JAK inhibitors include acne and gastrointestinal issues. In a phase 3 abrocitinib study, 15% of subjects experienced gastrointestinal disorders compared to 3% in the control group. Similarly, upadacitinib therapy for atopic dermatitis resulted in gastrointestinal issues in 7.1% of the treated cohort versus 2.5% in the placebo cohort. Acne was reported in 5%, 3%, and 9% of subjects taking abrocitinib, upadacitinib, and baricitinib, respectively, but was generally mild to moderate and manageable with topical treatments.
Implications for Healthcare Providers
The investigators suggest that the risks associated with JAK inhibitors in older RA patients with comorbidities are less concerning for younger, healthier individuals using these drugs for dermatologic conditions. They also noted that traditional systemic options for atopic dermatitis, such as cyclosporine, methotrexate, and oral corticosteroids, may carry similar or greater risks for VTE, malignancy, and MACE compared to JAK inhibitors like upadacitinib and abrocitinib.
To improve patient outcomes and adherence, healthcare providers should tailor educational efforts, use clear language, provide supplementary materials, and communicate associated risks sensitively. The researchers concluded that while the black box warning may reduce willingness to prescribe and accept JAK inhibitors, the overall safety profile in the ORALSURV study is reassuring when prescribing to younger, healthier patients with dermatologic conditions.
