Abstract
OBJECTIVE: To evaluate the efficacy of anti-CD3 monoclonal antibody (mAb) in patients with type 1 diabetes (T1D) and identify the influencing factors. METHODS: Randomized controlled trials comparing anti-CD3 mAb with placebo or standard care in T1D participants were screened from PubMed, Embase, and Cochrane databases until 31 May 2024. Changes in area under the curve (AUC) of C-peptide, HbA1c level and daily insulin requirement were main outcomes. Results were computed as standardized mean difference (SMD) and 95% confidence interval (CI). Meta-regression and subgroup analyses were also performed. RESULTS: Eleven eligible trials involving 1573 T1D participants were included in this meta-analysis. Compared with control group, anti-CD3 mAb significantly increased AUC of C-peptide (SMD = 0.337, 95% CI 0.105 to 0.569, P = 0.004) and decreased daily insulin requirement (SMD = - 0.598, 95% CI - 0.927 to - 0.269, P < 0.001). Subgroup analysis revealed that low average age (≤ 18 years old: SMD = 0.546, 95% CI 0.203 to 0.889, P < 0.001), high cumulative dose of anti-CD3 mAb (≥ 25 mg: SMD = 0.588, 95% CI 0.424 to 0.752, P < 0.001), and short T1D diagnosis duration before enrollment (≤ 6 weeks: SMD = 0.609, 95% CI 0.405 to 0.814, P < 0.001) were significantly associated with an increase in AUC of C-peptide. Notably, meta-regression analysis revealed that cumulative dose was the most critical factor, masking the effect of average age and T1D diagnosis duration. Most adverse events were transient and could be medically treated. CONCLUSION: Anti-CD3 mAb effectively preserves C-peptide secretion and reduces insulin requirement in patients with T1D. Younger age (≤ 18 years), earlier treatment initiation (≤ 6 weeks post-diagnosis), higher cumulative doses (≥ 25 mg) may present better therapeutic effect.