Comparative efficacy, safety, and functional recovery of neonatal fc receptor inhibitors and conventional immunotherapies for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and network meta-analysis.

BACKGROUND

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) management is undergoing a paradigm shift with the emergence of targeted biologicals. We aimed to compare the efficacy, safety, and functional outcomes of neonatal Fc receptor (FcRn) inhibitors against conventional immunotherapies.

METHODS

We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) indexed in PubMed/MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP from database inception to February 2026. Interventions included FcRn inhibitors (efgartigimod alfa, rozanolixizumab), intravenous/subcutaneous immunoglobulin (IVIg/SCIG), corticosteroids, plasma exchange (PLEX), and rituximab. The primary outcome was clinical response rate. Secondary outcomes included serious adverse events (SAEs), discontinuation due to adverse events (DCAE), and grip-strength change as a distal motor outcome. Treatments were ranked using P-scores, and certainty of evidence was summarized using CINeMA/GRADE domains.

FINDINGS: Eighteen RCTs (n=2,184) were included. In the primary efficacy network (I2 = 0.37%), PLEX (OR 33.60, 95% CI 3.15-358.90; P-score 0.9415) and corticosteroids (OR 15.44, 95% CI 3.53-67.47; P-score 0.9056) demonstrated the highest probability of achieving clinical response. Efgartigimod alfa showed significant clinical response (OR 3.14, 95% CI 1.34-7.33) and ranked highest for grip-strength change (SMD 0.67, 95% CI 0.09-1.24; P-score 0.8847), although this analysis was based on five studies and should be interpreted as a distal motor outcome rather than a comprehensive functional endpoint. For secondary outcomes, FcRn inhibitors had SAE estimates comparable to placebo (efgartigimod OR 1.00, 95% CI 0.31-3.20; rozanolixizumab OR 0.94, 95% CI 0.05-16.37), and rozanolixizumab ranked highest for DCAE/acceptability (P-score 0.7896). Heterogeneity was low to modest across secondary networks (SAEs I2 = 12.40%; DCAE I2 = 0.00%; grip strength I2 = 24.10%).

INTERPRETATION: PLEX and corticosteroids showed the strongest relative effects for short-term clinical response, whereas efgartigimod alfa showed a significant treatment effect and the highest ranking for grip-strength change among studies reporting this distal motor measure. IVIg remains a broadly supported comparator across induction and maintenance settings. These findings should inform, but not replace, individualized clinical decision-making because patient-level treatment-effect modification, biomarker status, prior treatment response, and long-term neurophysiological outcomes were not directly evaluated.