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, the recommended dose of Rinvoq is 15 mg once daily, while for atopic dermatitis, initiate with 15 mg once daily in patients under 65 years, with the option to escalate to 30 mg once daily if response is inadequate. 1

Rheumatoid Arthritis Dosing

• The standard dose is 15 mg once daily for adults with moderate to severe RA who have inadequate response to conventional synthetic DMARDs (csDMARDs). 1, 2
• No dose adjustment is required for any degree of renal impairment, distinguishing upadacitinib from other JAK inhibitors like baricitinib. 1, 3
• No dose adjustment is needed for mild to moderate hepatic impairment (Child-Pugh A or B), but upadacitinib is contraindicated in severe hepatic impairment (Child-Pugh C). 1, 3
• The 30 mg dose should not be used in rheumatoid arthritis, as only the 15 mg dose is FDA-approved for this indication. 3, 1
• Clinical response can be expected within 2-4 weeks, with maximal benefit by 3-6 months. 2

Efficacy Data for RA

• In the SELECT-NEXT trial, 64% of patients receiving upadacitinib 15 mg achieved ACR20 response at week 12 compared to 36% with placebo (p<0.0001). 4
• DAS28(CRP) ≤3.2 was achieved by 48% of patients on upadacitinib 15 mg versus 17% on placebo at week 12. 4
• In biologic-refractory patients (SELECT-BEYOND), 65% achieved ACR20 with upadacitinib 15 mg versus 28% with placebo at week 12. 5

Atopic Dermatitis Dosing

• For patients 12 years and older weighing at least 40 kg and adults under 65 years: initiate with 15 mg once daily. 1, 6
• If adequate response is not achieved, escalate to 30 mg once daily. 1, 6
• For adults 65 years and older: the recommended dose is 15 mg once daily only. 1
• Discontinue if adequate response is not achieved with the 30 mg dose; use the lowest effective dose to maintain response. 1
• For severe renal impairment (eGFR 15 to <30 mL/min/1.73m²), limit dose to 15 mg once daily. 1
• When using strong CYP3A4 inhibitors (e.g., ketoconazole), reduce dose to 15 mg once daily. 1

Efficacy Data for Atopic Dermatitis

• The 30 mg dose demonstrates the highest efficacy for reducing EASI scores among all currently available treatments in network meta-analysis and was superior to dupilumab in head-to-head trials. 6
• At week 16, the 30 mg dose achieved 74% mean improvement in EASI score versus 23% with placebo (p<0.001). 7
• The 15 mg dose is predicted to achieve EASI-75 in 48% of patients, while 30 mg provides approximately 20% greater efficacy. 8

Pre-Treatment Screening Requirements

Before initiating upadacitinib, the following screening is mandatory:

• Tuberculosis screening (tuberculin skin test or interferon-gamma release assay) per CDC guidelines. 2
• Hepatitis B and C testing. 2
• Complete blood count with differential, liver enzymes, renal function, and lipid panel. 2, 3
• Pregnancy testing in women of childbearing potential. 3
• HIV testing in high-risk populations. 2
• Vaccination for herpes zoster (recombinant, non-live vaccine) is recommended before initiation, particularly for older patients. 6

Monitoring During Treatment

• Check complete blood count with differential and liver enzymes at baseline and 4 weeks after initiation or dose escalation. 6, 3
• Check lipid panel at 12 weeks after initiation. 3
• Monitor regularly for signs of venous thromboembolism (chest pain, leg swelling, shortness of breath). 3
• The optimal frequency of ongoing laboratory monitoring for patients on continuous JAK inhibitor therapy remains unclear, but regular monitoring is recommended. 6

Critical Safety Warnings and Contraindications

FDA Black Box Warnings

• The FDA has issued black box warnings for all JAK inhibitors based on the ORAL Surveillance trial in RA patients ≥50 years with cardiovascular risk factors, showing increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancies, and death. 2, 3
• For patients ≥50 years with cardiovascular risk factors, biologics should be preferred over JAK inhibitors. 2

Specific Risk Populations

• Exercise caution in patients ≥65 years, current or long-term past smokers, those with cardiovascular risk factors, and those at increased malignancy risk. 3
• Upadacitinib is not recommended for patients with end-stage renal disease (eGFR <15 mL/min/1.73m²). 1

Infection Risks

• Increased risk of serious and opportunistic infections, including herpes zoster. 6, 9
• Rates of herpes zoster were higher with upadacitinib compared to methotrexate and adalimumab in the integrated phase III RA program. 9
• Interrupt treatment if a serious infection develops until the infection is controlled. 1

Other Safety Signals

• Rates of creatine phosphokinase (CPK) elevations were higher with both upadacitinib doses versus methotrexate and adalimumab. 9
• Gastrointestinal perforations occurred at higher rates with the 30 mg dose. 9
• Rates of malignancies, MACE, and VTE were similar among patients receiving upadacitinib, methotrexate, or adalimumab in the phase III RA program. 9

Common Pitfalls to Avoid

• Do not use the 30 mg dose for rheumatoid arthritis—only the 15 mg dose is approved for RA. 3, 1
• Do not overlook cardiovascular risk stratification—the ORAL Surveillance study demonstrated increased MACE and malignancy in high-risk RA patients with tofacitinib. 3
• Do not substitute RINVOQ LQ oral solution with RINVOQ extended-release tablets—they are not interchangeable, and changes should be made by the healthcare provider. 1
• Do not use in severe hepatic impairment (Child-Pugh C)—upadacitinib is contraindicated in this population. 1, 3

Drug Interactions

• No significant interactions with methotrexate when used in combination with upadacitinib. 3
• For patients receiving strong CYP3A4 inhibitors, reduce the dose to 15 mg once daily for atopic dermatitis, ulcerative colitis, and Crohn's disease. 1
• No dose adjustment needed for RA, psoriatic arthritis, ankylosing spondylitis, or polyarticular juvenile idiopathic arthritis when using strong CYP3A4 inhibitors. 1