What are the guidelines for using Tofacitinib in patients with autoimmune diseases and a history of infections?

Tofacitinib Use in Patients with Autoimmune Diseases and History of Infections

Tofacitinib can be used in patients with a history of recurrent or serious infections when TNF inhibitors are contraindicated, but active serious infections are an absolute contraindication requiring treatment completion before initiation. 1, 2

Absolute Contraindications Related to Infection

• Do not initiate tofacitinib during any active serious infection, including localized infections 2
• Active tuberculosis must be completely treated before starting tofacitinib 3, 2
• Any active bacterial, viral, fungal, or opportunistic infection requires resolution before initiation 3, 2

Pre-Treatment Infection Screening Requirements

All patients must undergo mandatory tuberculosis screening with interferon-gamma release assay (IGRA) or tuberculin skin test before starting tofacitinib 3, 2

• Obtain chest X-ray if not recently performed, particularly in patients with TB risk factors 3
• Test for hepatitis B and C antibody and RNA if clinically indicated 3
• Patients with latent TB must complete at least 1 month of anti-TB therapy before initiating tofacitinib 3, 2

When Tofacitinib Is Preferred Over TNF Inhibitors in Patients with Infection History

The 2018 ACR/NPF guidelines specifically recommend considering tofacitinib over TNF inhibitors in psoriatic arthritis patients with contraindications to TNF biologics, including previous serious infections, recurrent infections, congestive heart failure, or demyelinating disease 1, 4

• This conditional recommendation is based on low-quality evidence but reflects the clinical reality that tofacitinib may have a more favorable infection profile than TNF inhibitors in select patients 1
• Tofacitinib is also preferred over IL-17 inhibitors in patients with history of recurrent candida infections 4
• Abatacept is another alternative to consider in patients with recurrent or serious infections 1, 4

Infection Risk Profile with Tofacitinib

Serious infection rates with tofacitinib are comparable to biologic DMARDs, with incidence rates of 2.0-3.0 per 100 patient-years 5, 6

• In ulcerative colitis trials with 4.4 years of follow-up, the serious infection incidence rate was 2.0 (95% CI, 1.4-2.8) per 100 patient-years 5
• Meta-analysis of rheumatoid arthritis trials showed tofacitinib 5 mg twice daily had an incidence rate of 3.02 (95% CI, 2.25-4.05), comparable to TNF inhibitors at 4.90 (95% CI, 4.41-5.44) 6
• Risk ratio versus placebo for serious infections was 2.21 (95% CI, 0.60-8.14) for tofacitinib 5 mg twice daily 6

Critical Exception: Herpes Zoster Risk

Herpes zoster infection occurs at significantly elevated rates with tofacitinib, particularly at the 10 mg twice daily dose 5

• In UC maintenance trials, herpes zoster incidence rate was 6.6 per 100 patient-years (95% CI, 3.2-12.2) with tofacitinib 10 mg twice daily versus 1.0 (95% CI, 0.0-5.4) with placebo 5
• The 5 mg twice daily dose had an incidence rate of 2.1 (95% CI, 0.4-6.0) 5
• Recombinant zoster vaccine (Shingrix) must be administered before initiating tofacitinib, with a 2-dose series separated by 2-6 months 3

Dosing Considerations Based on Infection Risk

For patients with history of infections, use the lowest effective dose: 5 mg twice daily for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis 2

• In ulcerative colitis, induction requires 10 mg twice daily for 8 weeks (maximum 16 weeks), but maintenance should be 5 mg twice daily 2
• The 10 mg twice daily dose in UC was associated with greater risk of serious infections and opportunistic herpes zoster infections compared to 5 mg twice daily 2, 5
• Dose reduction to 5 mg once daily is required for moderate-to-severe renal impairment or moderate hepatic impairment 2

Monitoring During Treatment

Interrupt tofacitinib immediately if a patient develops a serious infection, opportunistic infection, or sepsis 2

• Monitor closely for signs and symptoms of infection during and after treatment 2
• Patients with chronic or recurrent infection history require heightened surveillance 2
• Complete blood count with differential should be checked at 4-8 weeks, then every 3 months 3
• Do not initiate if absolute lymphocyte count <500 cells/mm³, ANC <1000 cells/mm³, or hemoglobin <9 g/dL 2

Special Populations Requiring Extreme Caution

Patients over 65 years have significantly higher serious infection rates on tofacitinib compared to TNF inhibitors and should only receive tofacitinib if no alternative exists 3

• Patients with chronic lung disease or interstitial lung disease are more prone to infections 2
• Risk of infection increases with increasing degrees of lymphopenia 2
• Patients taking concomitant immunomodulating agents (methotrexate, corticosteroids) have higher infection risk 2

Common Clinical Pitfalls to Avoid

• Do not assume absence of symptoms equals absence of latent TB—formal IGRA or TST screening is mandatory even in asymptomatic patients 3
• Do not combine tofacitinib with other potent immunosuppressants or biologics, as this substantially increases infection risk 7
• Do not administer live vaccines during tofacitinib treatment 2
• Do not continue tofacitinib during active infection—interrupt therapy until infection resolves 2