Anti-C1q and Anti-C5 Therapies in Severe Guillain-Barré Syndrome: A Systematic Review and Bayesian Meta-analysis of Four Randomized Trials
Sindhu Vasireddy1, Shankar Biswas2, Yashasvi Srivastava2, Jignen Prajapati3, Simran Arora4, Anu Pillai5, Sai Pratibha Yandamuri6
1Neurology, NMC Specialty Hospital, 2Ivano Frankivsk National Medical University, 3Internal Medicine, Gujarat University, 4University of Debrecen, 5University of Dundee, 6Tbilisi State Medical University
Objective:
To synthesize all randomized evidence on complement-targeted therapies in severe Guillain-Barré syndrome using Bayesian meta-analysis, and to determine whether anti-C5 and anti-C1q inhibition differ in efficacy when structural confounding by IVIg co-administration is accounted for.
Background:

Standard treatment for severe Guillain-Barré syndrome has not changed in 30 years, and approximately 20% of patients remain unable to walk at 6 months. Eculizumab (anti-C5) and ANX005/tanruprubart (anti-C1q) have been tested in randomized placebo-controlled trials with discordant results, and no prior synthesis has integrated all available trials.

Design/Methods:

We searched PubMed, Embase, and Scopus through May 2026 for randomized double-blind placebo-controlled trials of complement inhibitors in adults with severe GBS. Three pre-specified pools were analysed using Bayesian random-effects meta-analysis (bayesmeta) with weakly informative priors: eculizumab + IVIg vs placebo + IVIg at week 4 (Pool A1) and week 24 (Pool A2), and ANX005 monotherapy vs placebo at week 8 (Pool B1). Frequentist Hartung-Knapp-Sidik-Jonkman analyses were fitted as cross-checks. Risk of bias was assessed with Cochrane RoB 2 and certainty of evidence with GRADE.

Results:

Four trials enrolling 382 patients were included. In Pool A1, the pooled risk ratio was 0.98 (95% credible interval, 0.52–1.94; posterior probability of benefit, 47%). Pool A2 was not interpretable owing to substantial heterogeneity (I², 81%; Q p = 0.021). In Pool B1, the pooled odds ratio was 2.17 (95% credible interval, 0.94–4.76; posterior probability of benefit, 96%; I², 0%). Drug class was perfectly confounded with IVIg co-administration. GRADE certainty was low for the two interpretable pools and very low for Pool A2.

Conclusions:

Anti-C1q monotherapy was associated with probable benefit on short-term outcomes. Anti-C5 added to IVIg was not. A randomized trial of tanruprubart against IVIg in a Western AIDP-predominant cohort is needed.

Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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