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

• 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 1
• Abatacept is another alternative to consider in patients with recurrent or serious infections 1

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 4, 5

• 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 4
• 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) 5
• Risk ratio versus placebo for serious infections was 2.21 (95% CI, 0.60-8.14) for tofacitinib 5 mg twice daily 5

Critical Exception: Herpes Zoster Risk

Herpes zoster infection occurs at significantly elevated rates with tofacitinib, particularly at the 10 mg twice daily dose 4

• 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 4
• The 5 mg twice daily dose had an incidence rate of 2.1 (95% CI, 0.4-6.0) 4
• 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, 4
• 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 6
• Do not administer live vaccines during tofacitinib treatment 2
• Do not continue tofacitinib during active infection—interrupt therapy until infection resolves 2