Can a patient with rheumatoid arthritis (RA) on hydroxychloroquine and leflunomide receive the zoster vaccine?

Zoster Vaccination in RA Patients on Hydroxychloroquine and Leflunomide

Yes, this patient should receive the recombinant zoster vaccine (Shingrix), as both hydroxychloroquine and leflunomide are non-biologic DMARDs that do not contraindicate vaccination, and the patient faces elevated herpes zoster risk from both the disease itself and leflunomide therapy.

Vaccine Selection: Shingrix is the Only Appropriate Option

• The recombinant zoster vaccine (RZV/Shingrix) is the recommended vaccine for all RA patients, as it is non-live and safe in immunocompromised individuals 1, 2.
• The live zoster vaccine (Zostavax) is explicitly not recommended for RA patients on DMARDs or biologics according to the 2012 ACR guidelines 1.
• Shingrix demonstrates 97.2% efficacy in preventing herpes zoster in adults aged 50 and older, with protection persisting for at least 8 years 2.

Why This Patient Needs Vaccination

• RA itself is an independent risk factor for herpes zoster, with patients having an increased baseline risk compared to the general population 1.
• Leflunomide specifically increases herpes zoster risk among non-biologic DMARDs (along with cyclophosphamide and azathioprine) 1.
• Hydroxychloroquine does not significantly increase herpes zoster risk and does not adversely impact vaccine response 1.
• A recent 2025 study demonstrated 60.7% vaccine effectiveness against herpes zoster and 88.7% effectiveness against postherpetic neuralgia in RA patients receiving 2 doses of Shingrix 3.

Safety Profile on Current Medications

• Vaccination can be safely administered during ongoing treatment with hydroxychloroquine and leflunomide without medication interruption 1.
• The 2011 EULAR guidelines explicitly state that vaccination can be administered during the use of disease-modifying antirheumatic drugs 1.
• A 2020 study of 403 rheumatic disease patients (239 with RA) showed only 6.7% experienced mild disease flares within 12 weeks of Shingrix vaccination, with no serious adverse events 4.
• The 2025 effectiveness study found no increased risk of RA flares within 30 days following RZV vaccination (RR 1.02,95% CI 0.75-1.37) 3.

Dosing Schedule and Administration

• Administer the standard 2-dose series with doses given 2-6 months apart 1, 2.
• The minimum interval between doses is 4 weeks; if given earlier, the dose should be repeated 2.
• No modifications to hydroxychloroquine or leflunomide dosing are required around vaccination 1.
• The vaccine is administered intramuscularly 2.

Important Clinical Considerations

• Verify that varicella zoster antibodies are positive before vaccination to prevent primary varicella infection with any residual vaccine strain concerns, though this is primarily relevant for live vaccines 1.
• Common side effects include injection-site reactions (9.5% grade 3 reactions) and systemic symptoms (11.4%), but these are generally mild and self-limited 2.
• The patient should receive vaccination regardless of prior herpes zoster history 2.
• If the patient is over 50 years old, vaccination is strongly recommended per CDC and ACR guidelines 1, 2.

Critical Pitfall to Avoid

Never administer the live zoster vaccine (Zostavax) to this patient—the 2012 ACR guidelines explicitly rate it as "not recommended" for RA patients on DMARDs, with a median appropriateness score of 1 1. Only Shingrix is appropriate for patients with rheumatic diseases on immunosuppressive therapy 1, 2.