Baricitinib

Baricitinib is an oral selective Janus kinase 1 and 2 inhibitor used in rheumatoid arthritis, alopecia areata, atopic dermatitis, juvenile idiopathic arthritis and hospitalised COVID-19. It is taken once daily and shares the class-wide cardiovascular, thrombotic, infection and malignancy cautions.

Class. Janus kinase inhibitor, targeted synthetic disease-modifying anti-rheumatic drug.

Mechanism. Reversible inhibition of JAK1 and JAK2, blocking signalling of interleukin 6, interferon gamma and other cytokines through signal transducer and activator of transcription proteins.

Pharmacokinetics. Bioavailability about 80 percent, peak at about 1 hour, half-life about 12 hours. About 75 percent is excreted unchanged in urine, so renal function directly determines exposure. It is a substrate of OAT3 and P-glycoprotein.

Rheumatoid arthritis (after inadequate response to conventional drugs).

• 4 mg orally once daily.

• Loading dose: none.

• Reduction: 2 mg once daily once disease is controlled, or from the start in patients aged 75 years and over and those with risk factors.

• Maximum dose: 4 mg daily.

Severe alopecia areata (adult). 2 mg once daily, increased to 4 mg once daily for inadequate response; use 2 mg for maintenance after response.

Moderate to severe atopic dermatitis (adult, where licensed). 4 mg once daily, 2 mg for patients with risk factors or after response.

Hospitalised COVID-19 (specialist). 4 mg once daily for up to 14 days or until discharge, with a corticosteroid.

Dose adjustments.

• eGFR 30 to 60 mL/min: 2 mg once daily. eGFR under 30 mL/min: avoid.

• Strong OAT3 inhibitors (probenecid): 2 mg once daily.

• Interrupt for lymphocytes under 0.5 x 10^9/L, neutrophils under 1.0 x 10^9/L, haemoglobin under 8 g/dL, or ALT and AST suspected drug injury.

Contraindications. Active serious infection including tuberculosis, pregnancy, and hypersensitivity. Avoid in severe hepatic impairment, and in active venous thromboembolism.

Boxed-warning-level risks. Serious infections, increased all-cause and cardiovascular mortality, malignancy, major adverse cardiovascular events, and thrombosis. Regulatory restrictions in many regions limit use in patients aged 65 years and over, long-term smokers, and those with cardiovascular or malignancy risk unless no suitable alternative exists.

Adverse effects. Common: upper respiratory infection, headache, nausea, herpes simplex and zoster, hypercholesterolaemia, raised transaminases, acne. Serious: herpes zoster, tuberculosis and opportunistic infection, venous thromboembolism, gastrointestinal perforation, neutropenia, lymphopenia, thrombocytosis, raised creatine kinase.

Major interactions. Probenecid (halve the dose), potent immunosuppressants such as ciclosporin and azathioprine (avoid), other biologics and JAK inhibitors (avoid), live vaccines (avoid).

Common prescribing errors. Not adjusting the dose for eGFR; using in high cardiovascular or thrombotic risk when alternatives exist; omitting lipid and blood count monitoring.

Special groups.

• Pregnancy: contraindicated; contraception during treatment and for at least 1 week after the last dose.

• Breastfeeding: avoid.

• Children: used in juvenile idiopathic arthritis in specialist care with weight-banded doses.

• Older adults: start at 2 mg once daily from 75 years; avoid where possible from 65 years.

• Kidney impairment: eGFR 30 to 60 mL/min, 2 mg once daily; under 30 mL/min, avoid.

• Liver impairment: avoid in severe impairment; monitor enzymes.

• Region: tuberculosis, hepatitis B and C and HIV screening before starting; consider recombinant zoster vaccination.

Formulations. 1, 2 and 4 mg film-coated tablets, taken once daily with or without food.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, full blood count with lymphocyte and neutrophil counts, ALT, AST, creatinine and eGFR, lipid profile, cardiovascular and thrombotic risk review, and vaccination update.

Monitoring. Full blood count and liver enzymes at 4 to 8 weeks then every 3 months; lipids 12 weeks after starting then every 6 to 12 months; renal function every 3 to 6 months; infection and thrombosis symptoms at each visit.

Stop or hold thresholds. Lymphocytes under 0.5 x 10^9/L (stop), neutrophils under 1.0 x 10^9/L (hold), haemoglobin under 8 g/dL (hold), serious infection, venous thromboembolism, or gastrointestinal perforation.

Referral and escalation. Specialist initiated. Refer for suspected thromboembolism, cardiovascular events, or persistent cytopenia.