Real-World Experience with Upadacitinib in Patients with Atopic Dermatitis and Hidradenitis Suppurativa: A Dual-Center Case Series

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurrent skin disorder that primarily affects the hair follicles. It is widely recognized as a debilitating condition with a complex and multifactorial pathogenesis involving genetic, immunological, and environmental factors. Clinically, HS is characterized by the development of painful, deep-seated nodules, abscesses, and sinus tracts that most commonly appear in intertriginous regions of the body such as the axillae, inframammary folds, groin, buttocks, and perineum. The disease often follows a relapsing course, significantly impairing quality of life for affected individuals.^1,2

Managing patients with moderate-to-severe HS continues to represent a considerable clinical challenge, as treatment frequently requires a combination of systemic therapies alongside meticulous local wound care. To date, only two biologic agents—adalimumab, an anti–TNF-α monoclonal antibody, and secukinumab, an IL-17A inhibitor—have received approval from both the FDA and EMA specifically for the treatment of HS. Despite these advances, many patients experience inadequate response or eventual loss of efficacy, highlighting the unmet need for additional therapeutic options.^3,4

Recently, Janus kinase (JAK) inhibitors have emerged as a promising new class of therapies for HS. Early clinical evidence, particularly from Phase II trials and real-world cohort studies, suggests that oral JAK1 inhibitors may provide meaningful clinical benefit. Several of these agents are now being further investigated in Phase III studies to better define their efficacy and safety profile.⁴

Upadacitinib, a selective JAK1 inhibitor, has already been approved for the treatment of multiple immune-mediated inflammatory diseases, including rheumatoid arthritis and atopic dermatitis (AD) in both adults and adolescents aged 12 years and older.⁴ Building on this background, we present a real-world case series evaluating the efficacy and safety of upadacitinib in patients with moderate-to-severe atopic dermatitis as well as in those with moderate-to-severe HS who had previously failed conventional biologic therapies such as TNF-α or IL-17 inhibitors.

In our study 10 patients with atopic dermatitis (AD) severe and refractory HS both were treated with upadacitinib at our department and at the department of Dermatology, Polytechnic Marche University, Ancona, Italy.

Dosing regimens varied based on patient’s comorbidities and disease severity: 8 patients received 30 mg daily and two received 15 mg daily. No concomitant systemic therapies were permitted. All patients received standard wound care and routine laboratory monitoring throughout treatment. The inclusion and exclusion criteria are the same as those used for all clinical studies conducted on HS and AD.

Patients were assessed at baseline, 4 months, and 12 months using the International Hidradenitis Suppurativa Severity Score System (IHS4), achievement of IHS4-55, Visual Analog Scale (VAS) for pain, and Dermatology Life Quality Index (DLQI) for HS while were assessed EASI (Eczema Area and Severity System), Peak Pruritus Numerical Rating Scale (PP-NRS) and DLQI for AD.

The cohort comprised 5 females and 5 males, with a mean age of 28.3 years (SD ±13.78) and mean BMI of 27.11 kg/m2 (SD ±3.11). Comorbidities and previous treatments are reported in Table 1.

Table 1 All the Patients Had AD and HS

Regarding AD at baseline, the mean EASI was 19.1, PP-NRS was 8.2 and DLQI was 17.7. At 4 months, these values improved to EASI =9.8, PP-NRS= 5 and DLQI = 9.3. At 12 months, further improvements were observed: EASI=4.7, PP-NRS= 0.2 and DLQI= 4.3 (Figure 1).

Figure 1 Data regarding Atopic Dermatitis score.

At baseline, the mean IHS4 score was 14; mean VAS pain score (HS), 6.2; and mean DLQI score (HS), 17.7. At 4 months, these values improved to IHS4 = 11, VAS = 5.6 and DLQI = 13.1. Only two patients reached the HiSCR score at week 16 and then three patients at week 48. At 12 months, further improvements were observed: IHS4 = 10.2, VAS = 5 and DLQI = 12 (Figure 2).

Figure 2 Data regarding Hidradenitis Suppurativa score.

No adverse events were reported across the follow-up period. Treatment was well tolerated across all dosing regimens.

Our real-world experience highlights the differential response to upadacitinib in patients with AD and HS. In the Phase 2 trial published regarding HS, upadacitinib 30 mg once daily improved lesions and pain in moderate-to-severe hidradenitis suppurativa, achieving HiSCR50 in 38% vs 25% (historical placebo) and pain NRS30 in 36% vs 22.5%, with a favorable safety profile supporting Phase 3 evaluation. Our findings are overall consistent with those from the phase 2 randomized trial.⁵

While patients with AD achieved marked clinical improvements across all outcomes, consistent with findings from published clinical trials and real-world studies, the response in HS, although present, was less pronounced and did not reach the same level of efficacy. These findings are noteworthy, as they suggest that while JAK1 inhibition may represent a valid therapeutic option for AD, its role in HS remains to be fully defined. Importantly, this observation emphasizes the need to refine patient selection or identify subgroups that might derive the greatest benefit from this approach.^3–5 We acknowledge the limitations of our small case series of 10 patients, yet we believe that our results add valuable real-world insights to the existing literature. Larger, controlled studies are urgently required to confirm whether upadacitinib could become an effective therapeutic option for HS in routine practice.