Study Identifies Approaches to Address Patient Fears Regarding JAK Inhibitor Safety

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Despite clinical research suggesting Janus Kinase (JAK) inhibitors have low serious adverse event risks, new findings suggest that conflicting information and doubts among patients may be addressed by speaking in simple phrases, offering educational resources, and decreasing anxiety through personal anecdotes.¹

These findings represent the conclusion of recent research conducted to highlight safety data and response options for health providers to use when discussing JAK inhibitor safety with dermatology patients. This study was led by Anthony J. Teixeira, from the department of dermatology at the Wake Forest University School of Medicine Center for Dermatology Research in North Carolina.

Teixeira et al. pointed to the fact that JAK inhibitors provide an option for individuals with failed or lost responses to biologic therapies. They noted that JAK inhibitors are suitable for patients not at risk of severe infections or at risk of thromboembolism.²

“In this article, we discuss recommendations from the literature on methods of discussing safety, and other treatment considerations, methods to put patients at ease, and the ethics of using specific phraseology to reassure patients,” Teixeira and colleagues wrote.¹

Findings on JAK Inhibitor Safety

The investigators looked at a variety of studies looking into safety data and various treatment considerations, with the goal of demonstrating methods of addressing related concerns. In 1 example, the JAK inhibitor tofacitinib, at doses of 5 mg and 10 mg per-day, was assessed in the Oral Surveillance (ORALSURV) study.

The trial was a randomized controlled phase 3b-4 study comparing tofacitinib to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) among individuals with diagnoses of rheumatoid arthritis (RA), looking at 4,362 RA patients aged 50 and older and each with at least a single cardiovascular risk factor. They found that while those treated with tofacitinib showed higher rates of major adverse cardiovascular events (MACE), such increases were not statistically significant, and the analysis could not establish non-inferiority of tofacitinib compared to TNF inhibitors.

This research had also highlighted rates of serious adverse events, venous thromboembolism (VTE), and infections. VTE was shown to develop among 1.2% of participants in the 5-mg tofacitinib cohort and 2.3% in the 10-mg cohort, versus 0.7% among the TNF inhibitor cohort.

The study found that serious adverse events were seen among 24.1% of those on 5-mg tofacitinib and 26.8% on 10-mg, versus the TNF cohort’s rate of 21.1%. The investigators noted that this study indicated infection risk was generally comparable across groups, though JAK inhibitors were shown to sometimes reactivate latent viral infections.

JAK Inhibitors for Dermatologic Indications

For dermatologic indications specifically, the research team noted that JAK inhibitors appeared to lead to fewer safety concerns, and this was particularly true among younger patients without comorbidities. The second-generation JAK1 inhibitor abrocitinib, which had been approved at doses of 100 mg and 200 mg per-day for atopic dermatitis, was noted to have shown in clinical research to carry minimal long-term VTE, MACE, or non-melanoma skin cancer (NMSC) risk.

For example, the team highlighted a 12-week phase 3 study looking into abrocitinib, during which treatment with the JAK1 inhibitor was not linked to any cardiovascular events, VTE, or cancer cases. Additionally, they had reported that serious adverse events were comparable between the abrocitinib and placebo arms.

The investigators noted that during another 12-week analysis, there were no malignancies or VTE observed by the study’s authors, though there had been a single case of sudden cardiac death in an elderly patient 3 weeks following discontinuation of treatment. However, this was determined to be unrelated to the drug.

After looking at a broader safety analysis assessing data from a variety of different trials, the research team found that rates of NMSC, VTE, serious adverse events, and MACE were shown to be slightly higher, but still minimal. This was especially the case with FDA-approved doses of abrocitinib.

Additional Findings

There are some adverse effects linked to dermatologic JAK inhibitors, such as acne and gastrointestinal issues. In the phase 3 abrocitinib study, it had been demonstrated that 15% of subjects experienced gastrointestinal disorders versus only 3% of controls. Similarly, in an analysis involving upadacitinib therapy for those with atopic dermatitis, gastrointestinal issues occurred in 7.1% of the treated cohort versus 2.5% in the placebo cohort, suggesting a heightened risk with JAK inhibitor implementation.

It was found that acne had been another side effect, with 5%, 3%, and 9% of subjects developing acne while taking abrocitinib, upadacitinib, and baricitinib, respectively. However, it was generally shown to be mild to moderate and managed using topical treatments.

Associated risks with use of JAK inhibitors among older rheumatoid arthritis patients with comorbidities were described by the investigators as less concerning for younger, healthier individuals using such drugs for dermatologic conditions. They added that systemic options traditionally used for atopic dermatitis, such as cyclosporine, methotrexate, and oral corticosteroids, may involve similar or even greater risks for VTE, malignancy, and MACE when compared to JAK inhibitors such as upadacitinib and abrocitinib.

For the purposes of enhancing outcomes among patients and ensuring adherence, given the apparent benefits of JAK inhibitors, healthcare providers were urged to overcome concerns by tailoring educational efforts. Utilization of clear language, the provision of supplementary educational materials, and careful communication regarding the associated risks in a way that is sensitive to individual patient needs was described as potentially helpful.

“The black box warning may reduce providers' willingness to prescribe and patients' acceptance of JAK inhibitors,” they wrote. “However, the overall safety profile observed in the landmark ORALSURV study in high-risk patients may be considered somewhat reassuring when prescribing JAK inhibitors to younger, healthier patients with dermatologic conditions who have fewer comorbidities.”¹

References

1. ^{Teixeira AJ, Duong JQ, Parraga SP, Feldman SR. Presenting JAK Inhibitor Safety Information to Dermatology Patients. JEADV Clin Pract. 2024; 1–9. https://doi.org/10.1002/jvc2.551.}
2. ^{Miot HA, Criado PR, de Castro CCS, Ianhez M, Talhari C, Ramos PM. JAK-STAT pathway inhibitors in dermatology. An Bras Dermatol. 2023; 98(5): 656–677. https://doi.org/10.1016/j.abd.2023.03.001.}