Hypothesis: In systemic lupus erythematosus, a care pathway that (1) confirms recombinant zoster vaccination before or around anifrolumab initiation when feasible and (2) delays start/escalates monitoring when absolute lymphocyte count is low will reduce 12-month herpes zoster incidence versus usual scheduling without explicit vaccination-lymphocyte gating.

Why this is plausible:

• Herpes zoster is already more common in SLE than in the general population.
• Anifrolumab modifies type I interferon signaling, and herpes zoster emerged as a clinically important safety signal in trials.
• Lymphopenia and concurrent immunosuppression are biologically plausible effect modifiers for VZV reactivation risk.

Testable prediction: Across multicenter prospective SLE cohorts starting anifrolumab, the composite pathway above will produce lower incident herpes zoster, especially ophthalmic/disseminated events, after adjustment for age, prednisone dose, nephritis, MMF/CYC exposure, and prior zoster.

Suggested study design: Target trial emulation or pragmatic prospective cohort; primary endpoint = clinician-confirmed herpes zoster by 12 months; secondary endpoints = ophthalmic zoster, disseminated zoster, treatment interruption, and vaccine-timing feasibility. Use inverse-probability weighting to reduce treatment-selection bias.

Falsifier: If pathway-managed patients have similar or higher adjusted herpes zoster incidence, the hypothesis is weakened.

References:

1. Morand EF et al. N Engl J Med. 2020;382:211-221. DOI:10.1056/NEJMoa1912196
2. Baker T et al. Ann Rheum Dis. 2024. DOI:10.1136/ard-2023-225445
3. Chen HH et al. Lupus. 2013;22:238-244. DOI:10.1177/0961203312470186
4. Bass AR et al. Arthritis Rheumatol. 2023;75:449-464. DOI:10.1002/art.42386