Upadacitinib Dosing for Giant Cell Arteritis
The recommended dose of upadacitinib for giant cell arteritis is 15 mg orally once daily, as this dose demonstrated superior efficacy compared to placebo in achieving sustained remission, while the 7.5 mg dose failed to show superiority. 1
Evidence-Based Dosing
Approved Dose
- Upadacitinib 15 mg once daily is the effective dose for GCA, combined with a 26-week glucocorticoid taper 1
- This dose achieved sustained remission in 46.4% of patients at week 52, compared to 29.0% with placebo (p=0.002) 1
- The 15 mg dose was superior to placebo across all key secondary endpoints including sustained complete remission, time to disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes 1
Ineffective Lower Dose
- Upadacitinib 7.5 mg once daily was NOT superior to placebo (41.1% vs 29.0% sustained remission, not statistically significant) 1
- This lower dose should not be used for GCA treatment 1
Clinical Context and Rationale
Role in GCA Treatment Algorithm
- Upadacitinib represents a JAK inhibitor option for GCA, blocking signaling of multiple cytokines including IL-6 and interferon-γ 1
- Current guidelines recommend adjunctive therapy for selected GCA patients with refractory/relapsing disease or those at increased risk of glucocorticoid-related adverse effects, with tocilizumab as first-line and methotrexate as alternative 2
- Upadacitinib at 15 mg provides an additional therapeutic option, particularly given its demonstrated glucocorticoid-sparing effects 1
Safety Profile
- Safety outcomes during the 52-week treatment period were similar between upadacitinib 15 mg and placebo groups 1
- Importantly, no major adverse cardiovascular events occurred in the upadacitinib groups, addressing a key concern with JAK inhibitors 1
- Two serious infections were reported in a Swedish case series of 15 patients using baricitinib/tofacitinib, though therapy was retained or reintroduced after recovery 3
Dose Modifications
No Renal Adjustment
- No dose adjustment is needed for renal impairment with upadacitinib 2
Hepatic Impairment
- Upadacitinib is contraindicated with severe hepatic impairment 2
Comparison to Other JAK Inhibitors
Baricitinib Dosing (for context)
- Baricitinib is approved at 4 mg once daily for rheumatoid arthritis, with 2 mg daily appropriate for patients ≥75 years, CrCl 30-60 mL/min, or history of chronic/recurrent infections 2
- Clinical experience with baricitinib in GCA shows encouraging results with significant CRP reductions at 3 and 6 months and prednisolone dose reductions 3
Important Caveats
- The 15 mg dose was studied specifically with a 26-week glucocorticoid taper, not as monotherapy 1
- The trial enrolled 70% patients with new-onset GCA and 30% with relapsing disease 1
- While promising, upadacitinib is not yet included in major GCA treatment guidelines (ACR 2021, EULAR 2018), as these predate the 2025 phase 3 trial results 2
- Do not use the 7.5 mg dose - it lacks demonstrated efficacy in GCA 1