2024-07-29 13:36:41
Background
Abrocitinib, a selective Janus kinase 1 inhibitor administered orally once daily, is effective for moderate to severe atopic dermatitis and has a manageable long-term safety profile.
Objective
Our objective was to provide updated and integrated results on the long-term safety of abrocitinib based on available data accumulated over nearly 4 years in patients with moderate to severe atopic dermatitis from the JADE clinical development program.
Methods
The analysis included 3,802 patients (exposure: 5,213.9 patient-years) from the phase II monotherapy study (NCT02780167) and from the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff date September 25, 2021). Data from patients who received one or more doses of abrocitinib 200 mg or 100 mg were grouped into a constant dose cohort (patients were assigned to receive the same dose of abrocitinib throughout their exposure in the qualifying main study and/or in the long-term study) or in a variable dose cohort (patients received abrocitinib 200 mg in an open-label manner; responders were randomly assigned to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue treatment). Rates of adverse events of special interest were assessed. A Cox regression analysis of risk factors for herpes zoster and serious infections was conducted.
Results
Overall, this long-term safety analysis of data up to nearly 4 years of exposure to abrocitinib does not indicate any change in the previously communicated risk profile. The most common serious infections (according to the preferred term of the Medical Dictionary for Regulatory Activities) with constant doses of abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with both doses), and herpes simplex (0.1% with both doses). Risk factors for herpes zoster included a history of herpes zoster, the 200 mg dose of abrocitinib, age ≥ 65 years, and an absolute lymphocyte count < 1000 cells/mm³ was a risk factor. The incidence rate/100 patient-years (95% confidence interval) with the combined constant dose of abrocitinib 200 mg and 100 mg was higher in older patients (≥ 65 years) compared to younger ones (18 to < 65 years).
Conclusions
This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate to severe atopic dermatitis. The risk of specific adverse events was higher in certain patient populations, particularly in those aged ≥ 65 years.
Eric L. Simpson, Jonathan I. Silverberg, Audrey Nosbaum, Kevin Winthrop, Emma Guttman-Yassky, Karin M. Hoffmeister, Alexander Egeberg, Hernan Valdez, Haiyun Fan, Saleem A. Farooqui, Gary Chan, Justine Alderfer, William Romero & Kanti Chittuluru
DOI: 10.1007/s40257-024-00869-w
Future Trends in Atopic Dermatitis Treatment: Focus on Abrocitinib
The growing prevalence of atopic dermatitis, particularly among patients with moderate to severe forms of the condition, has catalyzed a shift in treatment paradigms. Abrocitinib, a selective Janus kinase (JAK) inhibitor, has emerged as a pivotal player in this evolving landscape, demonstrating efficacy in managing symptoms and a manageable long-term safety profile.
Long-Term Safety Monitoring
Recent updates from long-term studies, assessing nearly four years of patient data, indicate that abrocitinib maintains a consistent safety profile without the emergence of new safety signals. This trend underscores the importance of continued safety monitoring as more patients adopt these oral treatments. Future clinical trials are likely to further investigate demographic-specific risks, especially among older populations, emphasizing the necessity of personalized medicine in this field.
Combination Therapies
Another potential trend is the exploration of combination therapies. The findings indicate that patients who responded positively to abrocitinib not only benefit from the medication itself but may also require adjunct treatments, such as topical corticosteroids. Future research may focus on optimizing these combination strategies to enhance therapeutic outcomes while minimizing adverse effects, particularly in susceptible patient populations.
Expanding Patient Profiles
As demographic data suggests varying risk profiles—like older patients facing increased complications—industry stakeholders will likely invest in research that broadens the understanding of how age, comorbidities, and genetic factors influence treatment efficacy and safety. This data will be essential for developing targeted therapies that cater to a diverse patient population, promising tailored approaches in managing atopic dermatitis.
Patient Education and Engagement
With the increasing complexity of treatment plans, patient education will become paramount. Future strategies may encompass more robust patient engagement initiatives, empowering individuals to understand their treatment choices, manage expectations regarding side effects, and adhere to prescribed therapies. As digital health tools gain traction, telemedicine and online support forums will likely become integral in facilitating effective communication between healthcare providers and patients.