What are the indications for Rinvoq (upadacitinib)?

Indications for Rinvoq (Upadacitinib)

Rinvoq (upadacitinib) is FDA-approved for the treatment of moderate to severe atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis, with specific requirements for each indication. 1

Approved Indications

Rheumatoid Arthritis

• Indicated for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers 1
• Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine 1
• Demonstrated superior efficacy compared to adalimumab in combination with methotrexate in head-to-head studies 2

Psoriatic Arthritis

• Indicated for adults and pediatric patients 2 years of age and older with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers 1
• Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants 1

Atopic Dermatitis

• Indicated for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable 1
• Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants 1
• Higher doses (30 mg daily) demonstrate the highest efficacy at reducing EASI scores and were superior to dupilumab in head-to-head clinical trials 2

Ulcerative Colitis

• Indicated for adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers 1
• Considered a "HIGHER efficacy medication" for ulcerative colitis according to AGA guidelines 2
• Not recommended for use in combination with other JAK inhibitors, biological therapies, or potent immunosuppressants 1

Crohn's Disease

• Indicated for adults with moderately to severely active Crohn's disease who have had an inadequate response or intolerance to one or more TNF blockers 1
• First oral agent shown to be effective and safe in both inducing and maintaining remission in Crohn's disease 2
• Not recommended for use in combination with other JAK inhibitors, biological therapies, or potent immunosuppressants 1

Ankylosing Spondylitis

• Indicated for adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers 1
• Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants 1

Non-radiographic Axial Spondyloarthritis

• Indicated for adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy 1
• Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants 1

Dosing Considerations

Standard Dosing

• Atopic dermatitis: 15 mg or 30 mg once daily 2
• Ulcerative colitis: 45 mg once daily for induction (8-16 weeks), followed by 15 mg or 30 mg once daily for maintenance 2
• Rheumatoid arthritis: 15 mg once daily 2
• Crohn's disease: Dosing varies, but typically 45 mg for induction followed by 15 or 30 mg for maintenance 2

Special Populations

• Renal impairment: Maximum recommended dosage is 15 mg daily for patients with severe renal impairment (creatinine clearance < 30 mL/min); no dosage adjustment needed for mild to moderate renal impairment 2
• Hepatic impairment: Not recommended in patients with severe hepatic disease (Child-Pugh C); no dosage adjustment needed for mild to moderate hepatic impairment 2
• Age considerations: Dose reduction to 15 mg daily may be appropriate for patients aged ≥75 years 2

Safety Considerations and Monitoring

Boxed Warnings

• Serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis 1
• Increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis 1

Monitoring Requirements

• Test for latent TB before and during therapy; treat latent TB prior to use 1
• Check complete blood count with differential, liver enzymes at baseline, and after initiation or dose-escalation 2
• Check lipids after initiation (4 weeks for abrocitinib, 12 weeks for upadacitinib) 2
• Testing for viral hepatitis, tuberculosis, and pregnancy should be performed at baseline 2

Risk Factors Requiring Special Consideration

• History of venous thromboembolism (VTE) 2
• Age > 65 years 2
• Current or previous long-term smokers 2
• History of cardiovascular disease 2
• History of cancer 2
• Pregnancy (limited data available, animal studies suggest potential adverse effects) 2

FDA Restrictions and Positioning

• JAK inhibitors have restricted use in treatment-naïve patients in the United States 2
• The FDA recommends the use of JAK inhibitors in patients with prior failure or intolerance to TNF antagonists 2
• In Europe, the European Medicines Agency recommends cautious use of JAK inhibitors as first-line agents in patients at risk for adverse cardiovascular outcomes 2

Clinical Efficacy

• Demonstrates rapid onset of action in clinical trials 3, 4
• Shows efficacy in patients with previous failure of biologic therapy 3
• Long-term safety profile has been consistent across multiple indications with over 27,000 patient-years of data 5
• Most studies suggest no statistically significant difference in safety outcomes compared to active treatments or placebo 6