Tofacitinib (Xeljanz): Indications and Dosing
FDA-Approved Indications
Tofacitinib is FDA-approved for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. 1
Rheumatoid Arthritis
Dosing
- Standard dose: 5 mg twice daily orally 1, 2
- Can be used as monotherapy or in combination with methotrexate or other conventional synthetic DMARDs 2
- Tofacitinib monotherapy after methotrexate withdrawal is effective in stable patients who have been on combination therapy for ≥24 months 3
Efficacy
- Tofacitinib 5 mg twice daily demonstrates superior ACR20, ACR50, and ACR70 response rates compared to placebo at 3 months 4
- When combined with methotrexate, tofacitinib is noninferior to adalimumab plus methotrexate for efficacy 2
- Benefits are sustained during long-term therapy up to 96 months 2
Psoriatic Arthritis
Dosing
Key Considerations
- In patients stable on tofacitinib 5 mg twice daily with background methotrexate for ≥24 months, methotrexate can be discontinued without clinically meaningful changes in disease activity 3
Ulcerative Colitis
Positioning in Treatment Algorithm
Tofacitinib should only be used after failure of or intolerance to TNF antagonists per FDA labeling. 5, 6 In biologic-naïve patients, the 2020 AGA guidelines recommend tofacitinib only be used within clinical or registry studies 5, though the 2024 update allows use with the caveat of restricted first-line use 5.
Induction Dosing
- Standard induction: 10 mg twice daily orally for 8 weeks 5, 7
- Extended induction: In patients with modest response at 8 weeks, 10 mg twice daily may be continued for up to 16 weeks total 5, 7
Maintenance Dosing
- Standard maintenance: 5 mg twice daily for most patients 5, 7
- Dose escalation: 10 mg twice daily may be considered in patients who lose response at 5 mg twice daily, but only after careful risk-benefit assessment 5, 7
Efficacy
- Tofacitinib demonstrates strong efficacy with relative risk for induction of remission of 3.22 (95% CI 2.03-5.08) and maintenance at 5 mg twice daily of 3.09 (95% CI 1.99-4.79) compared to placebo 5, 7
- The 2024 AGA guidelines classify tofacitinib as "intermediate efficacy," ranking below infliximab, vedolizumab, upadacitinib, and risankizumab 7
Critical Safety Warnings
Black Box Warnings
At the 10 mg twice daily maintenance dose, tofacitinib carries an unexpected increased risk of pulmonary embolism and all-cause mortality. 5, 7 The ORAL Surveillance trial in rheumatoid arthritis patients ≥50 years with cardiovascular risk factors demonstrated a five-fold increase in pulmonary embolism risk with 10 mg twice daily compared to TNF inhibitors 6, 8.
High-Risk Populations to Avoid
- Age ≥65 years with cardiovascular risk factors 5, 6
- Current or previous long-term smokers with cardiovascular disease 5, 6
- History of venous thromboembolism 7
- History of malignancy 7
- Uncontrolled cardiac risk factors 7
Infection Risks
- Serious infections including tuberculosis, opportunistic infections, and bacterial, fungal, and viral infections occur at higher rates than placebo 8
- Herpes zoster occurs at significantly higher rates with tofacitinib compared to TNF inhibitors and the general population 8, 2
- Zoster vaccination should be considered before initiating therapy, particularly in patients >70 years or >50 years at high risk 6, 8
- Screen for tuberculosis, hepatitis, and HIV before initiating therapy 6
Malignancy Risk
- Increased risk of lung cancer, breast cancer, and lymphoma compared to TNF inhibitors in high-risk populations 6, 8
Dose Adjustments
Renal Impairment
- Moderate to severe renal impairment: Reduce dose to 5 mg once daily 6
Hepatic Impairment
- Moderate hepatic impairment: Reduce dose to 5 mg once daily 6
- Severe hepatic impairment: Not recommended 6
Contraindications and Drug Interactions
Absolute Contraindications
Avoid Combinations
- Do not combine with potent immunosuppressants, biologics for inflammatory diseases, or tocilizumab/other IL-6 inhibitors 6
- Can be used with methotrexate and corticosteroids 6
Monitoring Requirements
Baseline Testing
- Tuberculosis screening 6
- Hepatitis and HIV screening 6
- Pregnancy test in all patients of childbearing potential 6
Laboratory Monitoring
- Do not initiate if lymphocyte count <500 cells/mm³, ANC <1000 cells/mm³, or hemoglobin <9 g/dL 8
- Discontinue if ANC <500 cells/mm³ 8
- Monitor for dose-related elevations in lipids (triglycerides, total cholesterol, LDL, HDL) 8
- Monitor liver enzymes (elevations >3× ULN have been recorded) 8
- Hold tofacitinib until hemoglobin normalizes if anemia develops 6
Critical Pitfalls to Avoid
Do not use tofacitinib as first-line therapy in biologic-naïve ulcerative colitis patients outside clinical trials 5, 7
Do not continue 10 mg twice daily maintenance indefinitely without reassessing risk-benefit due to thromboembolism and mortality risk 5, 7
Do not initiate in elderly patients (≥65 years) with cardiovascular risk factors without careful consideration 5, 6
Do not use in patients with inflammatory bowel disease and axial spondyloarthritis—TNF inhibitors are strongly preferred 5