One-year acne tolerability of abrocitinib versus upadacitinib in moderate-to-severe atopic dermatitis: an unanchored matching-adjusted indirect comparison

Introduction: Janus kinase inhibitors (JAKi), including abrocitinib and upadacitinib, are effective systemic therapies for moderate-to-severe atopic dermatitis (M2S AD) and have demonstrated superiority to dupilumab. Acne is a notable JAKi class-level adverse event observed across randomized clinical trials (RCTs) and real-world clinical practice. Acne is a burdensome adverse event that can undermine treatment adherence, persistence, and satisfaction in patients with M2S AD. The objective of this study was to provide indirect comparative data for risk of acne with high and low doses of abrocitinib versus upadacitinib over 1 year of treatment.Methods: Four abrocitinib monotherapy RCTs (JADE MONO 1 [NCT03349060], MONO 2 [NCT03575871], MOA [NCT03915496], and EXTEND [NCT03422822]) and 2 upadacitinib monotherapy RCTs (Measure Up 1 [NCT03569293] and Measure Up 2 [NCT03607422]) were included. Placebo crossover patients who later received abrocitinib/upadacitinib in the long-term extension study JADE EXTEND or long-term extension periods of Measure Up 1/2 were also included. Standard matching-adjusted indirect comparison methods were used for adjustments based on treatment effect modifiers. Odds ratios (OR) for acne with abrocitinib (200 or 100 mg) versus upadacitinib (30 or 15 mg) after up to 1 year of treatment were calculated. Results: Data from 774 patients treated with abrocitinib (100 mg, n=431; 200 mg, n=343) and 1608 patients treated with upadacitinib (15 mg, n=797; 30 mg, n=811) were included. There was evidence of higher odds of acne with upadacitinib 30 mg versus abrocitinib 200 mg (OR [95% CI], 3.39 [2.14-5.36]; P<0.0001), and with upadacitinib 15 mg versus abrocitinib 100 mg (OR [95% CI], 7.72 [3.72-16.01]; P<0.0001). Similarly, there was evidence of higher odds of acne with upadacitinib 30 mg versus abrocitinib 100 mg (OR [95% CI], 13.21 [6.41-27.21]; P<0.0001), and with upadacitinib 15 mg versus abrocitinib 200 mg (OR [95% CI], 1.98 (1.24-3.16); P=0.0045). Conclusions: Across both matched- and cross-dose comparisons, abrocitinib demonstrated a consistently favorable acne tolerability profile versus upadacitinib at 1 year—a clinically meaningful consideration for long-term JAKi selection in M2S AD. Notably, upadacitinib 30 and 15 mg were associated with nearly 3.5×, and over 7.5× higher odds of acne compared with abrocitinib 200 and 100 mg, respectively. For treatment with the lowest effective dose, abrocitinib 100 mg has a more tolerable acne safety profile than upadacitinib 15 mg, while abrocitinib 200 mg may be a more tolerable option than upadacitinib 30 or 15 mg for patients who require fast and durable skin clearance and itch relief. Funding: This study was sponsored by Pfizer.