JAK Inhibitor Prescribing

Janus kinase inhibitors are oral targeted synthetic disease-modifying drugs used in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, ulcerative colitis and atopic dermatitis. They match biologics for efficacy but carry boxed-warning-level risks: serious infection, mortality, malignancy, major cardiovascular events and venous thromboembolism.

Restriction. Use only when no suitable alternative exists in patients aged 65 or over, current or past long-term smokers, patients with other cardiovascular risk factors, and those with venous thromboembolism or malignancy risk.

Before starting. Optimise cardiovascular risk and confirm failure or contraindication of tumour necrosis factor inhibitors where applicable.

Regimens.

• Tofacitinib 5 mg orally twice daily (prolonged-release 11 mg once daily).
• Baricitinib 4 mg once daily; reduce to 2 mg once daily when disease is controlled, in older adults, or with eGFR 30 to 60 mL/min.
• Upadacitinib 15 mg once daily (30 mg in selected inflammatory bowel and skin disease, specialist only).
• Filgotinib 200 mg once daily; 100 mg daily if eGFR 15 to 59 mL/min or age 75 or over (availability varies).

Combination. With methotrexate for added effect; do not combine with biologics or other potent immunosuppressants.

Choice. Tofacitinib has the longest cardiovascular safety experience; baricitinib has once-daily dosing; selectivity does not remove the shared class warnings.

Kidney impairment. Baricitinib: avoid if eGFR under 30 mL/min. Tofacitinib: halve the dose to 5 mg once daily if eGFR under 30 mL/min. Upadacitinib: no change at eGFR 30 mL/min or more; limited data under 30. Filgotinib: 100 mg once daily if eGFR is 15 to 59 mL/min; avoid under 15 mL/min.

Liver impairment. Tofacitinib: halve the dose in moderate impairment and avoid in severe impairment. Baricitinib and upadacitinib: avoid in severe impairment.

Interactions.

• Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir, cobicistat): reduce tofacitinib to 5 mg once daily.
• Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John’s wort): lower levels; avoid.
• Probenecid: raises baricitinib levels; halve the dose.
• Live vaccines: avoid.

Pregnancy and breastfeeding. Avoid in both. Stop at least 1 week to 4 weeks before conception depending on the drug, and use contraception during treatment.

Vaccination. Give recombinant zoster vaccine before starting; herpes zoster rates are higher than with biologics.

Regional. Screen for tuberculosis, hepatitis B and C, and HIV before starting, exactly as before a biologic; tuberculosis risk is high in endemic settings. Use extra care with older and cardiovascular-risk patients, as monitoring is limited.

Baseline. Full blood count, creatinine, liver tests, fasting lipids, tuberculosis and hepatitis screening, cardiovascular risk review and a pregnancy test.

Ongoing. Full blood count and liver tests at 4 to 8 weeks then every 3 months. Lipids at 8 to 12 weeks, treating dyslipidaemia as needed. Creatine kinase if myalgia occurs. Skin checks each year.

Hold for: absolute neutrophil count under 1.0 x 10⁹/L, absolute lymphocyte count under 0.5 x 10⁹/L, haemoglobin under 8 g/dL or a fall of over 2 g/dL, ALT or AST over 3 times the upper limit, active serious infection or herpes zoster.

Stop and escalate. Stop for venous thromboembolism, arterial thrombosis, serious infection, gastrointestinal perforation, malignancy, myocardial infarction or stroke. Review stopping before major surgery (usually 1 to 2 weeks).