Guideline Evidence for Upadacitinib in Hidradenitis Suppurativa
Upadacitinib currently has NO formal guideline recommendations for hidradenitis suppurativa, as it remains an investigational agent without FDA approval for this indication. 1
Current Guideline Status
The most recent expert consensus statement on JAK inhibitors (2025) explicitly acknowledges that while clinical trial evidence exists for upadacitinib in hidradenitis suppurativa, this is not yet an approved indication. 1 This means upadacitinib cannot be recommended within standard treatment algorithms for HS at this time.
The 2019 and 2025 North American Clinical Management Guidelines for Hidradenitis Suppurativa make no mention of upadacitinib or any JAK inhibitors as treatment options. 1 These guidelines comprehensively address topical therapies, systemic antibiotics, adalimumab, infliximab, secukinumab, and ustekinumab, but JAK inhibitors are conspicuously absent from all treatment algorithms. 1, 2, 3
The 2025 British Association of Dermatologists guidelines similarly state there is insufficient evidence to recommend numerous therapies for HS, though upadacitinib is not specifically listed among the agents evaluated. 2
Clinical Trial Evidence (Not Guideline-Level)
While guidelines do not support upadacitinib use, a phase 2 randomized controlled trial (2025) demonstrated that upadacitinib 30 mg daily achieved HiSCR50 response in 38.3% of patients at week 12 versus a historical placebo rate of 25.0% (p=0.018). 4 However, comparison with the in-trial placebo group showed only a 14.7% adjusted difference (nominal p=0.087), and the sample size was small (47 patients on upadacitinib, 21 on placebo). 4
This single phase 2 trial does not constitute guideline-level evidence, particularly given the modest effect size and lack of comparison to standard-of-care therapies like adalimumab (which achieves HiSCR response rates of 42-59% at week 12). 2, 4
Current Guideline-Supported Treatment Algorithm
Since upadacitinib lacks guideline support, the evidence-based treatment pathway for moderate-to-severe HS remains:
First-line for moderate disease (Hurley Stage II): Clindamycin 300 mg twice daily plus rifampicin 300-600 mg daily for 10-12 weeks (response rates 71-93%). 1, 2, 3
First-line for severe disease (Hurley Stage III) or antibiotic failure: Adalimumab 160 mg at week 0,80 mg at week 2, then 40 mg weekly starting week 4 (HiSCR response 42-59% at week 12). 1, 2, 3
Second-line biologics after adalimumab failure: Infliximab, secukinumab, or ustekinumab. 1, 2, 3
Critical Limitations
The absence of guideline recommendations for upadacitinib reflects several critical gaps:
- No phase 3 trial data demonstrating superiority or non-inferiority to adalimumab (the FDA-approved standard). 1, 4
- No long-term safety data specific to HS populations. 4
- JAK inhibitors carry established risks including venous thromboembolism, malignancy (especially non-melanoma skin cancer), serious infections, and cytopenias—risks that must be weighed against modest efficacy signals. 1
- The 2025 phase 2 trial showed response rates numerically lower than adalimumab's established efficacy. 2, 4
Until phase 3 trials are completed and regulatory approval obtained, upadacitinib cannot be recommended within evidence-based HS treatment algorithms. 1 Case reports describing off-label use in refractory disease do not constitute guideline-level evidence and should not guide standard practice. 5, 6