Introduction
Rinvoq (upadacitinib) is an oral Janus kinase (JAK) inhibitor developed by AbbVie Inc. for the treatment of various autoimmune and inflammatory conditions. Approved by the FDA in August 2019, Rinvoq represents an important advancement in targeted immunomodulatory therapy, offering an alternative treatment option for patients with inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or biologic therapies.
Mechanism of Action
Upadacitinib functions as a selective and reversible inhibitor of JAK enzymes, with preferential inhibition of JAK1 over JAK2, JAK3, and TYK2. JAK enzymes mediate signaling of numerous cytokines and growth factors involved in immune cell function, inflammation, and hematopoiesis. By inhibiting JAK1-mediated cytokine signaling (including IL-6, IL-7, IL-15, and interferons), Rinvoq modulates the immune response and reduces inflammation in autoimmune conditions.
Indications
FDA-approved indications include:
- Moderate to severe rheumatoid arthritis in adults who have had an inadequate response or intolerance to methotrexate
- Active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers
- Moderate to severe atopic dermatitis in adults and adolescents 12 years of age and older whose disease is not adequately controlled with other systemic drug products
- Active ankylosing spondylitis in adults who have had an inadequate response or intolerance to one or more TNF blockers
- Moderate to severe ulcerative colitis in adults who have had an inadequate response or intolerance to one or more TNF blockers
Dosage and Administration
Standard dosing:- Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 15 mg once daily
- Atopic dermatitis: 15 mg or 30 mg once daily based on disease severity and response
- Ulcerative colitis: 45 mg once daily for 8 weeks, followed by 15 mg or 30 mg once daily
- Administer orally with or without food
- Tablets should be swallowed whole with water
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use caution in severe impairment
- Hepatic impairment: Not recommended in patients with severe hepatic impairment
- Elderly: Increased risk of serious infections; monitor closely
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 2-4 hours. Absolute bioavailability approximately 95%. Food does not clinically affect absorption. Distribution: Mean volume of distribution is 118 L. Protein binding is approximately 52%. Metabolism: Primarily metabolized by CYP3A4 with minor contributions from CYP2D6. Produces several inactive metabolites. Elimination: Mean elimination half-life is 8-14 hours. Excretion is primarily fecal (69%) with renal elimination accounting for 24% of the dose.Contraindications
- Hypersensitivity to upadacitinib or any component of the formulation
- Active serious infections, including localized infections
- Severe hepatic impairment
- Pregnancy (unless potential benefit outweighs risk)
Warnings and Precautions
Boxed Warning:- Serious infections leading to hospitalization or death
- Increased risk of all-cause mortality, major adverse cardiovascular events, and malignancy
- Thrombosis: Increased risk of deep vein thrombosis and pulmonary embolism
- Gastrointestinal perforations: Use with caution in patients at risk
- Laboratory abnormalities: Neutropenia, lymphopenia, anemia, lipid elevations
- Hepatic enzyme elevations: Monitor liver enzymes periodically
- Vaccinations: Avoid live vaccines during treatment
Drug Interactions
Strong CYP3A4 inhibitors: (e.g., ketoconazole, clarithromycin) - May increase upadacitinib exposure; consider dose reduction Strong CYP3A4 inducers: (e.g., rifampin, carbamazepine) - May decrease upadacitinib exposure; consider alternative therapy Immunosuppressants: (e.g., azathioprine, cyclosporine) - Concomitant use not recommended due to increased risk of infectionAdverse Effects
Common adverse reactions (≥1%):- Upper respiratory tract infections
- Nausea
- Increased blood creatine phosphokinase
- Headache
- Hypertension
- Acne
- Herpes zoster
- Fatigue
- Serious infections (pneumonia, cellulitis, herpes zoster)
- Malignancies (lymphoma, lung cancer)
- Major adverse cardiovascular events
- Thrombosis
- Gastrointestinal perforations
Monitoring Parameters
Baseline:- Complete blood count with differential
- Liver function tests
- Lipid panel
- Tuberculosis screening
- Viral hepatitis screening
- Pregnancy test (if applicable)
- CBC with differential (periodically)
- Liver enzymes (periodically)
- Lipid panel (4-8 weeks after initiation, then periodically)
- Signs and symptoms of infection
- Thrombotic events monitoring
- Skin examination for malignancies
Patient Education
- Take medication exactly as prescribed
- Report any signs of infection (fever, cough, shortness of breath)
- Seek immediate medical attention for symptoms of thrombosis (swelling, pain, redness in limbs)
- Inform healthcare providers about all medications being taken
- Avoid live vaccines during treatment
- Report any new or worsening symptoms
- Use effective contraception during treatment
- Regular follow-up appointments are essential
- Report any unusual skin changes or growths
References
1. FDA prescribing information: Rinvoq (upadacitinib). Revised 2023. 2. Smolen JS, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate: A phase 3 study. Lancet. 2019;393(10188):2303-2311. 3. Guttman-Yassky E, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis: Results from phase 3 studies. J Am Acad Dermatol. 2021;84(5):1225-1236. 4. Cohen SB, et al. Safety profile of upadacitinib in rheumatoid arthritis: Integrated analysis from the SELECT phase 3 clinical program. Arthritis Rheumatol. 2021;73(8):1371-1383. 5. Sandborn WJ, et al. Efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: Results from the U-ACHIEVE study. Gastroenterology. 2021;160(6):S-126. 6. Upadacitinib drug monograph. Lexicomp Online. Accessed January 2024.