Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2024; 15(8): 1793-1801
Published online Aug 15, 2024. doi: 10.4239/wjd.v15.i8.1793
Safety of teplizumab in patients with high-risk for diabetes mellitus type 1: A systematic review
Venkata Buddhavarapu, Gagandeep Dhillon, Harpreet Grewal, Pranjal Sharma, Rahul Kashyap, Salim Surani
Venkata Buddhavarapu, Department of Medicine, Banner Baywood Medical Center, Banner Health, Mesa, AZ 85206, United States
Gagandeep Dhillon, Department of Medicine, UM Baltimore Washington Medical Center, Glen Burnie, MD 21061, United States
Harpreet Grewal, Department of Radiology, Ascension Sacred Heart Hospital, Pensacola, FL 32504, United States
Pranjal Sharma, Department of Medicine, Northeast Ohio Medical Center, Rootstown, OH 44272, United States
Rahul Kashyap, Department of Research, Wellspan Health, York, PA 17403, United States
Rahul Kashyap, Salim Surani, Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States
Salim Surani, Department of Medicine & Pharmacology, Texas A&M University, College Station, TX 77843, United States
Author contributions: Buddhavarapu V, Dhillon G, Grewal HS and Sharma P designed the systematic review, acquired the data and interpreted the data; Buddhavarapu V, Kashyap R and Surani S drafted the article and made critical revisions; All authors were responsible for the final approval of the version submitted for publication.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Salim Surani, FACP, FCCP, MD, MHSc, Adjunct Professor, Department of Medicine & Pharmacology, Texas A&M University, 40 Bizzell Street, College Station, TX 77843, United States. srsurani@hotmail.com
Received: April 25, 2024
Revised: June 24, 2024
Accepted: July 17, 2024
Published online: August 15, 2024
Processing time: 91 Days and 16.7 Hours
Abstract
BACKGROUND

The incidence of diabetes mellitus type 1 (DM1) has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status. A new anti-CD4 antibody, Tep-lizumab, has been shown to delay the progression of DM1 and is the only medication approved for this indication. However, more information is needed about the safety profile of this drug.

AIM

To identify the odds ratios (OR) of systems-based adverse effects for Teplizumab when compared to Placebo.

METHODS

An extensive systematic review was conducted from the inception of the medication until December 31, 2023. All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review. The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO (ID: CRD42024496169). Crude OR were generated using RevMan Software version 5.4.

RESULTS

After screening and review, 5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo. A total of 561 patients were included in the study population. Total adverse effects and system-based adverse effects were studied and reported. We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal (GI) (OR = 1.60, 95%CI: 1.01-2.52, P = 0.04), dermatological (OR = 6.33, 95%CI: 4.05-9.88, P < 0.00001) and hematological adverse effects (OR = 19.03, 95%CI: 11.09-32.66, P < 0.00001). These patients were also significantly likely to have active Epstein-Barr Virus infection (OR = 3.16, 95%CI: 1.51-6.64, P < 0.002). While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo, this finding did not reach statistical significance (OR = 2.25, 95%CI: 0.80-6.29, P = 0.12).

CONCLUSION

Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects, primarily related to GI, dermatological, and hematological systems. The total adverse effect data is limited as study populations are small. More studies should be conducted on this medication to better inform the target population of potential adverse effects.

Keywords: Teplizumab; Diabetes mellitus type 1; Adverse effects; Monoclonal antibody; Systematic review

Core Tip: Teplizumab is an anti-CD4 antibody that has been shown to delay the clinical onset of diabetes mellitus type 1. Our systematic review evaluates the incidence of total adverse effects and a systems-based risk reported in various clinical trials. Our review shows an increased incidence of adverse effects in patients receiving Teplizumab compared to placebo, but this risk is not statistically significant. There is also a statistically significant increased risk of gastrointestinal, dermatological, and hematological adverse effects in the Teplizumab group compared to placebo. More trials need to be conducted to understand better the risk of side effects related to Teplizumab.