Safety and Efficacy of Teplizumab for Treatment of Type One Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

Background:: Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti-CD3 monoclonal antibody, which may have beneficial effects for T1DM patients. Objective:: To assess the safety and efficacy of teplizumab in T1DM patients. Methods:: We searched electronic databases using related keywords for randomized clinical trials that assessing the safety and efficacy of teplizumab. We evaluated the retrieved citations for eligibility, and we extracted the data then analyzed it using Review Manager Software. Results:: We included eight randomized clinical trials with 866 patients. Teplizumab was associated with lower insulin use than placebo at 6 months (MD = -0.17, 95% CI [-0.24, -0.09], P < 0.001), 12 months (MD = -0.12, 95% CI [-0.18, -0.06], P < 0.001), 18 months (MD = -0.22, 95% CI [-0.32, -0.11], P < 0.001) and 24 months (MD = -0.17, 95% CI [-0.28, -0.06], P = 0.003). The area under the curve of C-peptide was significantly increased in teplizumab group at 12 months (MD = 0.08, 95% CI [0.01, 0.15], P = 0.03), 18 months (MD = 0.13, 95% CI [0.01, 0.25], P = 0.03) and 24 months (MD = 0.13, 95% CI [0.01, 0.24], P = 0.03). No significant effect of teplizumab on HbA1c levels at any time point. Teplizumab was associated with some side effects such as lymphopenia, skin and subcutaneous tissue disorders. Conclusions:: Teplizumab is associated with lower insulin use and higher AUC of C-peptide in type 1 diabetic patients with no significant effect on Hb1c levels. Besides, teplizumab showed some adverse effects.

Efficacy of anti‐CD3 monoclonal antibodies in delaying the progression of recent‐onset type 1 diabetes mellitus: A systematic review, meta‐analyses and meta‐regression

“…Another study by Nourelden et al 33 assessed the efficacy of teplizumab as a treatment for T1DM. Their study included a systematic review of relevant articles, analysed using a review manager.…”

Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis

“…Previous clinical trials of peptide immunotherapy found that 10 μg C19-A3 proinsulin peptide s.c. every 2 weeks was well tolerated in patients with recent-onset T1D ( 31 ), while 60–150 μg weekly s.c. administration of celiac disease–relevant peptides induced dose-dependent gastrointestinal symptoms associated with T cell IL-2 production ( 32 – 34 ). Similarly, proinflammatory adverse effects of anti-CD3 immunotherapy in T1D were dose dependent ( 35 ). Taken together, we hypothesize that transient increases in joint symptoms after a 3 mL dose correspond to the strength of TCR signaling.…”

Teplizumab – preventative approaches to type 1 diabetes mellitus

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