Dose Adjustment of JAK Inhibitors for the Management of Moderate-to-Severe Atopic Dermatitis: A Single-Centre...

Background and Objectives: Janus kinase (JAK) inhibitors have expanded the therapeutic options for moderate-to-severe atopic dermatitis (AD). The possibility of dose modulation with abrocitinib (100 and 200 mg) and upadacitinib (15 and 30 mg), both selective JAK1 inhibitors, represents a potential clinical advantage, allowing dose escalation in cases of insufficient response and dose de-escalation in the setting of poor tolerability or during maintenance treatment. However, real-world data remain limited, and the rationale for dose adjustment is not always standardized. This study aimed to describe, using a real-world database, the frequency, timing, and reasons for dose modifications of these agents. Materials and Methods: We retrospectively analyzed the clinical data of 212 patients with moderate-to-severe AD treated with abrocitinib (n = 47) or upadacitinib (n = 165). Dose adjustments, including dose escalation and dose de-escalation, were recorded together with their timing and clinical reasons. Results: In the abrocitinib group, 34/47 patients (72.3%) initiated treatment at 100 mg, whereas 13/47 patients (27.7%) started at 200 mg. Six patients (12.8%) underwent a dose adjustment. One patient (2.1%) switched from 200 to 100 mg because of complete AD remission and concomitant menstrual cycle alterations, whereas five patients (10.6%) underwent dose escalation from 100 to 200 mg because of incomplete disease control. Among the six abrocitinib-treated patients who underwent dose adjustment, achievement of IGA 0/1 after dose modification was documented in all cases. In the upadacitinib group, 93/165 patients (56.4%) started at 15 mg, whereas 72/165 patients (43.6%) started at 30 mg. Overall, 44/165 patients (26.7%) underwent at least one dose adjustment, accounting for a total of 50 dose modifications: 27 escalations from 15 to 30 mg and 23 de-escalations from 30 to 15 mg. Among patients initiating treatment at 15 mg, 23/93 patients (24.7%) increased the dose to 30 mg after a median of 33.1 weeks because of suboptimal disease control. Among those starting at 30 mg, 21/72 patients (29.2%) reduced the dose to 15 mg after a median of 44.3 weeks. Of these, 12/21 patients (57.1%) reduced the dose because of adverse events, including herpetic infections and acne, whereas the remaining patients de-escalated because of optimal disease control. Some patients underwent multiple dose modifications: four followed a 30→15→30 mg sequence, with re-escalation after 13.2 weeks because of suboptimal disease control, and two followed a 15→30→15 mg sequence, with dose reduction after approximately 26.7 weeks because of herpes zoster. Overall, 29/44 patients achieved IGA 0/1 within 16 weeks and 38/44 within 32 weeks after dose modification. Conclusions: In this real-world cohort, dose adjustments of selective JAK1 inhibitors were frequently performed in patients with moderate-to-severe AD, particularly among those treated with upadacitinib. Dose escalation was mainly used to address suboptimal disease control, whereas dose de-escalation was performed in the setting of adverse events or optimal disease control. The availability of two dosing regimens may allow treatment intensity to be adapted to individual disease severity, response, and tolerability, supporting a personalized approach to AD management.