What are the indications and usage of Rinvoq (upadacitinib)?

Rinvoq (Upadacitinib) Indications and Usage

Rinvoq is FDA-approved for seven distinct indications in adults: moderately to severely active rheumatoid arthritis, active psoriatic arthritis, refractory moderate-to-severe atopic dermatitis, moderately to severely active ulcerative colitis, moderately to severely active Crohn's disease, active ankylosing spondylitis, and active non-radiographic axial spondyloarthritis—all specifically after inadequate response or intolerance to one or more TNF blockers. 1

FDA-Approved Indications

Rheumatoid Arthritis

• Approved for adults with moderately to severely active rheumatoid arthritis who have had inadequate response or intolerance to one or more TNF blockers 1
• Standard dosing is 15 mg once daily 2
• Demonstrated superiority to adalimumab in head-to-head studies when combined with methotrexate 2
• Not recommended in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine 1

Psoriatic Arthritis

• Approved for adults and pediatric patients 2 years of age and older with active psoriatic arthritis who have had inadequate response or intolerance to one or more TNF blockers 1
• In patients refractory to biologics, upadacitinib 15 mg achieved 56.9% ACR20 response and 30 mg achieved 63.8% versus 24.1% with placebo at week 12 3
• At week 24, minimal disease activity was achieved by 25.1% (15 mg) and 28.9% (30 mg) versus 2.8% with placebo 3
• Not recommended in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants 1

Atopic Dermatitis

• Approved 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
• The American Academy of Dermatology strongly recommends upadacitinib for adults with moderate-to-severe atopic dermatitis 4
• Standard dosing is 15 mg or 30 mg once daily 2
• Higher doses (30 mg daily) demonstrate the highest efficacy at reducing EASI scores and were superior to dupilumab in head-to-head trials 2
• Not recommended in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants 1

Ulcerative Colitis

• Approved for adults with moderately to severely active ulcerative colitis who have had inadequate response or intolerance to one or more TNF blockers 1
• The American Gastroenterological Association considers Rinvoq a "HIGHER efficacy medication" for ulcerative colitis 2
• Standard dosing is 45 mg once daily for induction (8-16 weeks), followed by 15 mg or 30 mg once daily for maintenance 2
• Superior to placebo in inducing and maintaining both clinical and endoscopic remission 5
• Not recommended in combination with other JAK inhibitors, biological therapies for ulcerative colitis, or potent immunosuppressants 1

Crohn's Disease

• Approved for adults with moderately to severely active Crohn's disease who have had inadequate response or intolerance to one or more TNF blockers 1
• The European Crohn's and Colitis Organisation strongly recommends upadacitinib as induction therapy with high-quality evidence 6
• Typical dosing is 45 mg for induction followed by 15 mg or 30 mg for maintenance 2
• Clinical remission rates of 44.4% versus 25.1% with placebo (p<0.001), with endoscopic response of 40.2% versus 8.4% 6
• Not recommended in combination with other JAK inhibitors, biological therapies for Crohn's disease, or potent immunosuppressants 1

Ankylosing Spondylitis

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

Non-Radiographic Axial Spondyloarthritis

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

Special Population Dosing Adjustments

Renal Impairment

• For patients with severe renal impairment (creatinine clearance < 30 mL/min), the maximum recommended dosage is 15 mg daily 2

Hepatic Impairment

• For patients with severe hepatic disease (Child-Pugh C), Rinvoq is not recommended 2

Elderly Patients

• Dose reduction to 15 mg daily may be appropriate for patients aged ≥75 years 2

Critical Pre-Treatment Requirements

Mandatory Screening

• Testing for viral hepatitis, tuberculosis, and pregnancy must be performed at baseline 2
• Update immunizations before initiating treatment 6
• Screen for active and latent tuberculosis 6
• Complete blood count with differential and liver enzymes should be checked at baseline 2

Baseline Laboratory Monitoring

• Lipids should be checked after initiation (12 weeks for upadacitinib) 2
• Complete blood count with differential and liver enzymes at baseline and after initiation or dose-escalation 2

High-Risk Populations Requiring Special Consideration

Cardiovascular and Thrombotic Risk

• History of venous thromboembolism (VTE) requires special consideration 2
• Age > 65 years is a risk factor requiring special consideration 2
• Current or previous long-term smokers are at increased risk 2
• History of cardiovascular disease requires special consideration 2
• The FDA recommends use of JAK inhibitors in patients with prior failure or intolerance to TNF antagonists 2
• The European Medicines Agency recommends cautious use as first-line agents in patients at risk for adverse cardiovascular outcomes 2

Malignancy History

• History of cancer is a risk factor requiring special consideration 2

Pregnancy

• Pregnancy requires special consideration, as limited data is available and animal studies suggest potential adverse effects 2

Safety Monitoring During Treatment

Laboratory Monitoring

• Interrupt treatment if absolute neutrophil count is less than 1000 cells/mm³ 6
• Interrupt treatment if absolute lymphocyte count is less than 500 cells/mm³ 6
• Monitor for herpes zoster infection, which occurs more frequently with JAK inhibitors 7

Positioning in Treatment Algorithms

The FDA specifically recommends use of JAK inhibitors such as Rinvoq in patients with prior failure or intolerance to TNF antagonists, establishing it as a second-line or later therapy across all approved indications. 2, 1