JAK inhibitors

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Dosing and administration^[3]

Oral targeted synthetic DMARDs. The doses below are the standard approved rheumatoid arthritis doses. A class boxed warning applies (see the note). Screen for latent tuberculosis and viral hepatitis before starting.

Onset. Onset is relatively rapid, often within 2 weeks.

Renal adjustment. Dose reduction is needed in moderate to severe renal impairment (agent-specific); review each product monograph.

Hepatic. Use with per-agent adjustment in hepatic impairment; not recommended in severe hepatic impairment.

Class boxed warning (from the ORAL Surveillance trial of tofacitinib): increased risk of serious infection, major adverse cardiovascular events, venous thromboembolism, malignancy, and all-cause mortality, particularly in patients 50 years or older with at least one cardiovascular risk factor. Generally reserved for patients with an inadequate response or intolerance to TNF inhibitors, and individualised by risk.

Monitoring

• Baseline and periodic complete blood count (lymphocytes, neutrophils, hemoglobin), liver enzymes, and lipids.
• Screen for latent tuberculosis and viral hepatitis; herpes zoster risk (consider vaccination).
• Assess cardiovascular and venous thromboembolism risk before and during treatment.

Contraindications

• Active serious infection, including active tuberculosis.
• Severe hepatic impairment.
• Pregnancy.
• Combination with biologic DMARDs or other potent immunosuppressants.

Key interactions

• Strong CYP3A4 inhibitors or inducers affect some agents (agent-specific dose adjustment).
• Do not combine with biologic DMARDs or another JAK inhibitor.
• Avoid live vaccines.

Clinical notes

Common side effects

Increased risk of infection including herpes zoster; laboratory changes including lipids and cytopenias. Not sourced on this draft.

Tests and monitoring

Before starting, screen for latent tuberculosis using the approach ACR applies to biologics; the 2015 ACR guideline extends this TB screening to tofacitinib (IGRA preferred after prior BCG; anergy testing is not recommended). Give indicated killed or inactivated vaccines beforehand, and in patients 50 years or older ACR suggests the herpes zoster vaccine before starting; live vaccines are not recommended during treatment. ACR does not set on-treatment laboratory intervals for this class and lists it as an evidence gap, so baseline and periodic CBC, lipids, and liver enzymes follow the product monograph. The class safety considerations (venous thromboembolism, major adverse cardiovascular events, and malignancy) are from the product labelling, not these ACR treatment guidelines. Recommendations derived for rheumatoid arthritis.^{[1, 2]}

Important cautions

Class safety considerations include venous thromboembolism, major adverse cardiovascular events, and malignancy, with risk concentrated in specific higher-risk groups; individualise patient selection. Live-vaccine timing applies. Risk magnitudes and eligibility criteria to confirm from primary sources.

References

1. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784. doi:10.1002/art.23721 https://doi.org/10.1002/art.23721
2. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1-25. doi:10.1002/acr.22783 (published simultaneously in Arthritis & Rheumatology) https://doi.org/10.1002/acr.22783
3. Standard approved rheumatoid arthritis doses from the respective Health Canada product monographs: tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq); class safety per the ORAL Surveillance trial. https://health-products.canada.ca/dpd-bdpp/