# Antimeningococcal Protection in Patients Receiving Terminal Complement Inhibitors

## TL;DR

Patients on C5 inhibitors face meningococcal risks; combining vaccination with antibiotics offers better protection than vaccination alone.

## Contribution

Demonstrates that combined vaccination and antibiotic prophylaxis significantly reduces meningococcal disease risk in C5 inhibitor recipients.

## Key findings

- Combined protection (vaccination + antibiotics) reduced IMD risk by 6-fold compared to single protection.
- Low booster vaccination coverage and antibiotic adherence were observed in C5 inhibitor recipients.
- Serogroup B caused most infections, with most patients recovering fully.

## Abstract

C5 inhibitor (C5i) therapy markedly increases susceptibility to invasive meningococcal disease (IMD) by blocking the terminal complement pathway essential for defense against Neisseria meningitidis. Vaccination is recommended for all recipients, yet breakthrough infections persist. Antibiotic prophylaxis is not universally endorsed, resulting in variable practices. We aimed to assess whether antibiotic prophylaxis provides additional protection beyond vaccination in C5i-treated patients.

The analysis included 124 C5i recipients treated for > 6 months. Patients were classified as receiving single protection (vaccination or antibiotic prophylaxis alone) or combined protection (vaccination and continuous antibiotic prophylaxis). The outcomes were analyzed by prescribed and by implemented regimen; the latter accounting for patient adherence to antibiotic prophylaxis.

Of the patients, 60% were prescribed combined protection. Booster vaccination coverage was low (< 40%), and one-quarter of patients did not adhere to antibiotic prophylaxis. The overall incidence of IMD was 0.74 cases per 100 patient-years (PY) (95% confidence interval [CI]: 0.37–1.32). After accounting for noncompliance, the incidence of IMD remained significantly lower in the combined protection group (3.1 [95% CI: 1.5–4.8] vs. 0.5 [95% CI: 0.0–2.7], P = 0.03), corresponding to a 6-fold reduction in risk. Eleven infections were reported, predominantly due to serogroup B (45.5%). Ten patients recovered completely, and 1 had mild residual disability.

Although guidelines recommend vaccination alone, our findings indicate that combined protection offers substantially greater protection against IMD in patients receiving long-term C5i. Continued prospective monitoring will be essential to define the optimal preventive strategies in this high-risk population.