Data from over 5200 patients with exposure up to 4 years.

Background

Abrocitinib, an orally administered, once-daily, selective Janus kinase 1 inhibitor, is effective in moderate to severe atopic dermatitis and has a manageable long-term safety profile.

Target

Our objective was to provide updated and comprehensive results on the long-term safety of abrocitinib based on available data accumulated over a maximum of almost 4 years in patients with moderate to severe atopic dermatitis in the JADE clinical trial program.

Methods

The analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and 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 submission deadline September 25, 2021). Data from patients who received one or more doses of 200 mg or 100 mg abrocitinib were pooled into a constant-dose cohort (patients were assigned to receive the same dose of abrocitinib throughout the exposure period in a qualified parent study and/or a long-term study) or a variable-dose cohort (patients received 200 mg abrocitinib in an open-label fashion; responders were randomly assigned to receive 200 mg, 100 mg, or placebo abrocitinib and could then receive 200 mg abrocitinib plus topical corticosteroids as rescue therapy). The incidence of adverse events of special interest was assessed. Cox regression analyses of risk factors for herpes zoster and serious infections were performed.

Results

Overall, this analysis of long-term safety data over a maximum of ~4 years of abrocitinib dosing does not indicate any change from the previously reported risk profile. The most common serious infections (per Medical Dictionary Preferred Term for Regulatory Activities) at the 200 mg and 100 mg constant doses of abrocitinib were herpes zoster (0.5% and 0.2%), pneumonia (0.2% at both doses), and herpes simplex (0.1% at both doses). Risk factors for herpes zoster were history of herpes zoster, abrocitinib dose 200 mg, age ≥ 65 years, and absolute lymphocyte count at 100 kg body weight. The incidence rate per 100 patient-years (95% CI) with the combined fixed dose of abrocitinib 200 mg and 100 mg was higher in elderly patients (≥ 65 years) compared with younger patients (18 to 100 mg).

conclusions

This safety update demonstrated a stable abrocitinib profile with no new safety signals and continues to support a manageable long-term safety profile of abrocitinib in patients with moderate to severe atopic dermatitis. The risk of specific adverse events was higher in certain patient groups, particularly those aged ≥65 years.

Eric L. Simpson, Jonathan I. Silverberg, Audrey Nosbaum, Kevin Winthrop, Emma Gutman-Yassky, Karin M. Hoffmeister, Alexander Egeberg, Hernan Valdez, Haiyun Fan, Salim A. Farooqi, Gary Chan, Justine Alderfer, William Romero, and Kanti Chittuluru

DOI: 10.1007/s40257-024-00869-w