Recommended Dose of Upadacitinib in Axial Spondyloarthritis
The recommended dose of upadacitinib for adults with active axial spondyloarthritis (both ankylosing spondylitis and non-radiographic axSpA) is 15 mg once daily. 1, 2
Standard Dosing
- Upadacitinib 15 mg once daily is the approved and studied dose for all forms of axial spondyloarthritis, including both radiographic (ankylosing spondylitis) and non-radiographic disease 3, 4, 5, 6
- This dose has demonstrated sustained efficacy through 2 years of treatment in clinical trials, with ASAS40 response rates of approximately 66-86% (as-observed) and 57-66% (non-responder imputation) 3, 4, 5
- The 15 mg once daily dose is taken continuously without induction or maintenance phase adjustments, unlike some other JAK inhibitors used in inflammatory bowel disease 1, 2
Dose Modifications for Special Populations
Severe renal impairment (creatinine clearance <30 mL/min): Maximum dose is 15 mg daily, which is already the standard dose for axSpA 2
Severe hepatic disease (Child-Pugh C): Upadacitinib is not recommended 2
Age ≥75 years: Consider dose reduction to 15 mg daily (already the standard dose for axSpA), though this recommendation comes from other indications where higher doses are used 2
Patients ≥65 years with cardiovascular risk factors: Use upadacitinib only if no suitable alternatives exist, but maintain the 15 mg daily dose if prescribed 1, 2
Critical Positioning in Treatment Algorithm
- Upadacitinib should be initiated after inadequate response to NSAIDs at maximum dose for at least 1 month 1, 7
- Current guidelines strongly recommend prioritizing biologic DMARDs (TNF inhibitors or IL-17 inhibitors) over JAK inhibitors as first-line advanced therapy, reserving upadacitinib for when biologics are contraindicated or unavailable 1
- The FDA and European Medicines Agency recommend JAK inhibitors after failure or intolerance to TNF antagonists, particularly in patients with cardiovascular risk factors 2
Efficacy Data Supporting This Dose
- In biologic-experienced patients with AS, upadacitinib 15 mg daily achieved ASAS40 in 66% at week 52 (NRI-MI analysis) 8
- In non-radiographic axSpA, upadacitinib 15 mg daily achieved ASAS40 in 45% at week 14 versus 23% with placebo (p<0.0001) 6
- MRI inflammation scores showed mean reductions of -7.3 to -7.9 in spine and -4.9 to -5.3 in sacroiliac joints at 2 years 3
Common Pitfalls to Avoid
Do not use higher doses: Unlike atopic dermatitis (15-30 mg) or ulcerative colitis (45 mg induction), axSpA requires only 15 mg daily 2
Do not combine with methotrexate: Unlike tofacitinib in psoriatic arthritis, upadacitinib does not require concomitant methotrexate in axSpA 1
Do not use as first-line in high-risk patients: Avoid in patients ≥65 years with smoking history or cardiovascular risk factors unless biologics have failed or are contraindicated 1, 2
Do not abruptly discontinue: If tapering is considered after sustained remission ≥12 months, reduce dose or extend intervals gradually rather than stopping abruptly 1, 7