What is the recommended use and dosage of Rinvoq (upadacitinib) for treating rheumatoid arthritis and atopic dermatitis?

Rinvoq (Upadacitinib): Recommended Use and Dosing

For rheumatoid arthritis, use upadacitinib 15 mg once daily in patients with inadequate response to conventional synthetic DMARDs, and for moderate to severe atopic dermatitis, initiate 15 mg once daily with escalation to 30 mg once daily if needed for adequate response in patients under 65 years. 1, 2, 3

Rheumatoid Arthritis

Indication and Positioning

• Upadacitinib is indicated for moderate to severe active rheumatoid arthritis in patients who have had inadequate response or intolerance to one or more conventional synthetic DMARDs (csDMARDs) 3
• The 2020 EULAR guidelines position JAK inhibitors after inadequate response to at least one bDMARD, or when a bDMARD is not appropriate, though this positioning may evolve as new data emerge 1
• Upadacitinib demonstrated statistical superiority over adalimumab in combination with methotrexate in clinical trials, though the overall clinical relevance of small differences was not considered convincing enough to prefer JAK inhibitors over biologics 1

Dosing

• The FDA-approved dose is 15 mg once daily 2, 3
• The 30 mg dose should never be used for rheumatoid arthritis, as only the 15 mg dose is approved for this indication 2, 3
• No dose adjustment is required for any degree of renal impairment, distinguishing upadacitinib from other JAK inhibitors like baricitinib 2
• Upadacitinib is contraindicated in severe hepatic impairment (Child-Pugh C), but no adjustment is needed for mild to moderate hepatic impairment 2, 3

Efficacy Data

• In the SELECT-NEXT trial of patients with inadequate response to csDMARDs, 64% achieved ACR20 with 15 mg and 66% with 30 mg versus 36% with placebo at week 12 4
• In the SELECT-BEYOND trial of patients refractory to biologic DMARDs, 65% achieved ACR20 with 15 mg and 56% with 30 mg versus 28% with placebo 5

Atopic Dermatitis

Indication and Positioning

• Upadacitinib is strongly recommended for adults with moderate to severe atopic dermatitis by the 2024 American Academy of Dermatology guidelines (strong recommendation, moderate certainty evidence) 1
• FDA approval requires that patients have failed other systemic therapies (pills or injections, including biologics) or when use of those therapies is inadvisable 1, 3

Dosing Strategy

• For patients under 65 years: Initiate 15 mg once daily; if inadequate response, increase to 30 mg once daily 2, 3
• For patients 65 years and older: Use only 15 mg once daily 3
• The 30 mg dose demonstrates the highest efficacy for reducing EASI scores among all available treatments in network meta-analysis 1
• Use the lowest effective dose needed to maintain response; discontinue if adequate response is not achieved with 30 mg 3

Efficacy Data

• The 15 mg dose is predicted to achieve EASI-75 in 48% of patients versus 9% with placebo 6
• The 30 mg dose provides approximately 20% greater efficacy for EASI-75, EASI-90, and IGA 0/1 endpoints relative to 15 mg 6
• In the phase 2b trial, mean EASI improvement was 62% with 15 mg and 74% with 30 mg versus 23% with placebo at week 16 7

Critical Safety Considerations and Monitoring

Pre-Treatment Screening (Required)

• Tuberculosis screening: Active and latent TB evaluation; treat if positive before initiating upadacitinib 2, 3
• Viral hepatitis screening: Do not initiate in patients with active hepatitis B or C 3
• Complete blood count: Do not initiate if absolute lymphocyte count <500 cells/mm³, absolute neutrophil count <1000 cells/mm³, or hemoglobin <8 g/dL 3
• Pregnancy testing: Verify pregnancy status in females of reproductive potential before starting 3
• Baseline labs: Liver enzymes, renal function, lipid panel 2

High-Risk Populations Requiring Caution

• Age ≥65 years: The EMA recommends caution; use only 15 mg dose for atopic dermatitis 2, 3
• Cardiovascular risk factors: Exercise caution based on ORAL surveillance study findings with tofacitinib showing increased MACE and malignancy in high-risk RA patients over 50 2, 8
• Current or long-term past smokers: EMA recommends caution with all JAK inhibitors 2
• Increased malignancy risk: Use caution in patients at increased risk 2

Ongoing Monitoring Protocol

• CBC with differential and liver enzymes: Check at 4 weeks after initiation or dose escalation, then periodically 1, 2
• Lipid panel: Check at 12 weeks after initiation 1, 2
• Monitor for VTE signs: Chest pain, leg swelling, shortness of breath 2

Key Safety Signals

• Herpes zoster: Rates higher with upadacitinib versus adalimumab; consider recombinant zoster vaccine before initiating, particularly in older patients 1, 9
• Serious infections: Rates similar between upadacitinib 15 mg and adalimumab but higher than methotrexate 9
• Venous thromboembolism: Thromboembolic events have occurred; use with caution in patients with VTE risk factors 1, 2
• CPK elevations: Higher rates with upadacitinib versus comparators 9
• Malignancies, MACE, VTE: Rates similar across upadacitinib, methotrexate, and adalimumab in phase III RA trials 9

Contraindications and Drug Interactions

• Do not combine with: Other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine 3
• No significant interactions with methotrexate when used in combination 2

Common Pitfalls to Avoid

• Never use 30 mg for rheumatoid arthritis - only approved for atopic dermatitis, ulcerative colitis, and Crohn's disease 2, 3
• Do not overlook cardiovascular risk stratification - the class warning from tofacitinib data applies to all JAK inhibitors 2, 8
• Do not substitute RINVOQ LQ oral solution with RINVOQ extended-release tablets - they are not interchangeable 3
• Do not split, crush, or chew tablets - must be swallowed whole 3