What are the vaccination guidelines for patients before and after starting upadacitinib (Janus kinase inhibitor) therapy?

Vaccination Guidelines for Upadacitinib Therapy

Complete all indicated vaccinations before starting upadacitinib, with particular emphasis on the recombinant zoster vaccine (Shingrix), which should be administered as a 2-dose series separated by 2-6 months for all patients ≥18 years old. 1, 2

Pre-Treatment Vaccination Requirements

Herpes Zoster Vaccination (Highest Priority)

• Administer recombinant zoster vaccine (Shingrix) before initiating upadacitinib as herpes zoster reactivation is clearly increased with JAK inhibitors, with incidence rates of 3-4 per 100 patient-years in Western populations and up to 9 per 100 patient-years in Asian populations. 1
• The 2-dose Shingrix series should be separated by 2-6 months and completed prior to treatment initiation whenever clinically feasible. 1, 2
• If the recombinant vaccine is unavailable, the live zoster vaccine (Zostavax) must be administered at least 3-4 weeks before starting upadacitinib, though its efficacy is questionable. 1, 3
• Risk factors for zoster reactivation include age, female gender, concomitant prednisone >7.5 mg daily, and hospitalization. 1

Additional Recommended Vaccines Before Treatment

• Inactivated pneumococcal vaccine should be administered for patients ≥18 years old. 1, 3
• Annual influenza vaccine (inactivated formulation only) is recommended. 1, 3
• All other indicated non-live vaccines should be completed before treatment initiation, as JAK inhibitors impair vaccine responses by blocking interferon pathways. 1, 3

Live Vaccine Restrictions

• All live vaccines must be administered at least 3-4 weeks before initiating upadacitinib to allow adequate immune response development. 1, 3
• Live vaccines are contraindicated once upadacitinib therapy has begun due to immunosuppression. 1

Vaccination During Upadacitinib Therapy

COVID-19 Vaccination

• Consider a 1-week pause of upadacitinib treatment after COVID-19 vaccination to prevent insufficient vaccination response, though this recommendation should be balanced against local and national health authority guidelines. 1
• Non-live COVID-19 vaccines with higher efficacies should be the first choice. 1

Immunogenicity on Treatment

• Recent data demonstrate that most patients (87.8%) receiving upadacitinib 15 mg daily with background methotrexate achieved satisfactory humoral responses to RZV when vaccinated during treatment, with over 60% achieving cell-mediated immune responses. 4
• Age and concomitant corticosteroid use did not significantly affect RZV antibody response in patients on upadacitinib. 4

Management of Herpes Zoster Breakthrough

If Zoster Develops on Treatment

• Temporarily interrupt upadacitinib treatment until the herpes zoster episode completely resolves. 1
• A small proportion of patients can develop recurrent zoster; antiviral prophylaxis could be considered in such individuals. 1
• In clinical trials, herpes zoster rates ranged from 2.4-6.6 per 100 patient-years across different indications, with most cases being mild to moderate. 5

Critical Pre-Treatment Screening Beyond Vaccination

Mandatory Infectious Disease Screening

• Screen all patients for latent tuberculosis using interferon-gamma release assay (IGRA) or tuberculin skin test, as TB reactivation risk with JAK inhibitors is similar to TNF inhibitors. 1, 2
• Complete at least 1 month of latent TB treatment before initiating upadacitinib if positive. 2
• Test for hepatitis B virus (anti-HBs, anti-HBc, HBsAg) and hepatitis C virus in all patients. 1, 2
• Obtain chest X-ray if not recently performed, particularly in high-risk patients. 1, 2

Baseline Laboratory Testing

• Complete blood count with differential to ensure safe initiation thresholds are met. 2
• Comprehensive metabolic panel including liver enzymes and renal function tests. 2
• Lipid profile at baseline, as JAK inhibitors cause dose-dependent lipid elevations. 2

Common Pitfalls to Avoid

• Do not delay vaccination series unnecessarily, but recognize that certain clinical scenarios make treatment delays challenging; in such cases, prioritize Shingrix vaccination above others. 1
• Do not assume absence of symptoms equals absence of latent TB; formal screening with IGRA or TST is mandatory even in asymptomatic patients. 2
• Do not initiate upadacitinib in patients with any active serious infection, including localized infections, until the infection is completely resolved. 2
• Do not combine upadacitinib with other biologic DMARDs or potent immunosuppressive agents (cyclosporine, tacrolimus) due to increased immunosuppression risk. 1