Upadacitinib Shows Promise for Hidradenitis Suppurativa but Lacks Guideline Support
Based on emerging phase 2 trial data, upadacitinib demonstrates efficacy for moderate-to-severe hidradenitis suppurativa (HS), but it is not currently recommended in established guidelines and should be considered investigational pending phase 3 trial results.
Current Guideline Position
The major HS guidelines do not include upadacitinib as a recommended treatment option:
British Association of Dermatologists (2019) explicitly states there is insufficient evidence to recommend JAK inhibitors for HS, listing them among therapies that cannot be recommended due to lack of data 1
North American guidelines (2019) do not mention JAK inhibitors for HS treatment, focusing instead on adalimumab as the primary biologic option 1
Standard treatment algorithm remains: topical clindamycin for mild disease, oral antibiotics (tetracyclines or clindamycin/rifampicin) for moderate disease, and adalimumab 160mg→80mg→40mg weekly for severe/refractory cases 2, 3
Emerging Clinical Evidence for Upadacitinib
Despite guideline silence, recent research provides encouraging data:
Phase 2 Trial Results (2025)
The most recent and highest-quality evidence comes from a randomized, placebo-controlled phase 2 trial 4:
Primary endpoint achieved: 38.3% of patients on upadacitinib 30mg daily achieved HiSCR50 (≥50% reduction in abscesses/nodules) at week 12 versus 25% historical placebo rate (p=0.018) 4
Response maintained: HiSCR50 achievement was sustained through week 40 with continued treatment 4
Consistent across subgroups: Efficacy was similar regardless of baseline Hurley stage or prior TNF inhibitor exposure 4
Safety profile: Consistent with known upadacitinib safety data from other dermatologic conditions 4
Real-World Case Reports
Additional supporting evidence includes:
- A pediatric case report demonstrated successful monotherapy with upadacitinib for concurrent HS and ulcerative colitis after failure of infliximab and ustekinumab, with clinical improvement within 3 months 5
Clinical Context and Limitations
Why Upadacitinib Isn't in Guidelines Yet
The 2019 guidelines predate the phase 2 trial data, which was only published in 2025 1, 4. Guidelines typically require:
- Multiple phase 3 trials
- FDA/regulatory approval for the specific indication
- Long-term safety data in the target population
Current FDA Status
- Upadacitinib is not FDA-approved for HS 5
- It is approved for atopic dermatitis (ages 12+), rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis 1
- Use in HS would be off-label
Practical Clinical Approach
When to Consider Upadacitinib for HS
Given the lack of guideline support but emerging evidence, consider upadacitinib in the following scenario:
- Moderate-to-severe HS (Hurley stage II-III) 4
- Failed conventional therapy: Inadequate response to oral antibiotics (tetracyclines, clindamycin/rifampicin) 2, 3
- Failed or contraindicated adalimumab: Either primary/secondary failure or patient cannot use TNF inhibitors 4
- Patient counseled about off-label use and investigational status
Dosing Based on Available Data
- Upadacitinib 30mg orally once daily was the effective dose in the phase 2 trial 4
- Expect response assessment at 12 weeks, with potential for continued improvement through 40 weeks 4
Monitoring Requirements
Based on JAK inhibitor class recommendations for other conditions 1:
- Baseline: Complete blood count, liver enzymes, lipid panel, tuberculosis screening, viral hepatitis screening, pregnancy test 1
- After initiation: Recheck labs per routine management (CBC and liver enzymes within 4-12 weeks) 1
- Ongoing: Monitor for infections, particularly herpes zoster (increased risk with JAK inhibitors) 1
Important Caveats
Safety Considerations
- JAK inhibitors carry FDA boxed warnings for serious infections, malignancy, cardiovascular events, and thrombosis based on data from other conditions 1
- The 10mg twice-daily tofacitinib dose was associated with venous thromboembolism and pulmonary embolism in RA patients 1
- Long-term safety specifically in HS populations remains unknown 4
Alternative Evidence-Based Options
Before considering upadacitinib, ensure trial of:
- Adalimumab: Only FDA-approved biologic for HS (ages 12+), with HiSCR response rates of 42-59% at week 12 2
- Infliximab: Recommended second-line biologic (5mg/kg at weeks 0,2,6, then every 8 weeks) 2, 3
- Ustekinumab: While also lacking guideline support, has more published case series data showing 76% clinical improvement in systematic review 6, 7
Comparison to Other Off-Label Biologics
Ustekinumab has more real-world evidence (45 published cases with 76% improvement rate) compared to upadacitinib's single phase 2 trial 6, 7. However, upadacitinib's phase 2 data is more rigorous (randomized, placebo-controlled) than ustekinumab's case series 4, 6.
Bottom Line for Practice
Upadacitinib should currently be considered an investigational option for moderate-to-severe HS after failure of guideline-recommended therapies (antibiotics, adalimumab, infliximab). The phase 2 data is promising but insufficient for guideline inclusion 4. Await phase 3 trial results before considering this a standard treatment option. If used off-label, ensure comprehensive informed consent about investigational status, careful patient selection, and appropriate safety monitoring per JAK inhibitor class recommendations 1, 4.