Anti-CD3 monoclonal antibody in treating patients with type 1 diabetes: an updated systematic review and meta-analysis.

Summary

Across 11 RCTs (n=1,573), anti-CD3 mAbs preserved beta-cell function (increased C-peptide AUC) and reduced daily insulin needs. Greater benefits were observed with higher cumulative dose (≥25 mg), earlier initiation (≤6 weeks post-diagnosis), and in younger patients; dose emerged as the dominant modifier.

Key Findings

• Anti-CD3 mAbs increased C-peptide AUC (SMD 0.337; 95% CI 0.105–0.569) and reduced daily insulin requirement (SMD −0.598; 95% CI −0.927 to −0.269).
• Stronger efficacy with higher cumulative dose (≥25 mg), earlier initiation (≤6 weeks post-diagnosis), and age ≤18 years.
• Meta-regression identified cumulative dose as the dominant modifier, attenuating effects of age and time from diagnosis.
• Most adverse events were transient and medically manageable.

Clinical Implications

Consider early initiation of anti-CD3 therapy soon after T1D diagnosis, aiming for adequate cumulative dosing, particularly in younger patients. Most adverse events are transient and manageable.

Limitations

• Use of standardized mean differences may limit direct clinical interpretability across assays.
• Heterogeneity in specific anti-CD3 agents, dosing regimens, and follow-up durations; long-term outcomes remain uncertain.

Future Directions

Head-to-head trials optimizing dosing and timing; evaluation of long-term clinical outcomes (hypoglycemia, complications), and combination strategies with other disease-modifying agents.