Apr 17, 2025

Public workspaceInfection related adverse events in adult patients with severe asthma treated with Tezepelumab, a systematic review and meta-analysis V.2

DOI
dx.doi.org/10.17504/protocols.io.3byl4zkn8vo5/v2
  • 1Northwest Medical Center;
  • 2Department of Hospital Medicine, Meritus Medical center, Hagerstown, Maryland;
  • 3School of Medicine, Univalle, Cochabamba, Bolivia.
Felix Reyes
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DOI: dx.doi.org/10.17504/protocols.io.3byl4zkn8vo5/v2
Protocol Citation: Felix Reyes, Tanvi Tiwari, Eduardo Saadi Neto 2025. Infection related adverse events in adult patients with severe asthma treated with Tezepelumab, a systematic review and meta-analysis. protocols.io https://dx.doi.org/10.17504/protocols.io.3byl4zkn8vo5/v2Version created by Felix Reyes
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: April 13, 2025
Last Modified: April 17, 2025
Protocol Integer ID: 126840
Keywords: Severe Asthma, Tezepelumab, Adverse drug reactions
Abstract
Asthma is a chronic respiratory disease with different phenotypes that are characterized by chronic airway inflammation. Severe asthma is a subset of difficult-to-treat asthma defined as uncontrolled asthma despite adherence to treatment with maximal optimized high-doses of ICS-LABA. Tezepelumab is a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), a key cytokine involved in airway inflammation. It is approved for the treatment of severe asthma to reduce exacerbations and improve lung function. TSLP plays a role in response to several infections.
Prior meta-analyses have focused on determining safety and efficacy. In these studies infections were only analyzed as secondary outcomes. We aim to identify the risk of infection in patients with severe asthma undergoing therapy with Tezepelumab.
Search Strategy
Search Strategy
ezspire("Severe asthma" OR "uncontrolled asthma") AND (tezepelumab OR "anti thymic stromal lymphopoietin" OR "anti-TSLP" OR tezspire) AND ("randomized controlled trial"[PT] OR "controlled clinical trial"[Publication Type] OR "randomized"[Title/Abstract] OR "placebo"[Title/Abstract] OR "drug therapy"[MeSH Subheading] OR ("randomly"[Title/Abstract] OR "trial"[Title/Abstract] OR "groups"[Title/Abstract])) NOT ("animals"[MeSH Terms] NOT "humans"[MeSH Terms])

Cochrane search:
("Severe asthma" OR "uncontrolled asthma") AND (tezepelumab OR "anti thymic stromal lymphopoietin" OR "anti-TSLP" OR tezspire)
Eligibility Criteria
Eligibility Criteria
We will include studies evaluating patients with severe asthma despite optimal therapy, irrespective of age, sex, country, and ethnic group. Randomized controlled trial the study must compare Tezepelumab to placebo.

We will exclude studies involving patients with documented Asthma-COPD Overlap syndrome, other severe pulmonary diseases and children (under 18 years of age). If a study reports active smokers, we will exclude active smokers from analysis.

We excluded non-human studies and in vitro research, editorials, conference proceedings, commentaries, expert opinion, reviews, studies without original data, non-English publications, and duplicate publications.
Intervention(s), exposure(s)
Intervention(s), exposure(s)
Therapy with tezepelumab
Comparator/control
Comparator/control
Placebo
Types of study to be included
Types of study to be included
Randomized control trial
Context
Context
We will include only studies that report on any of the outcomes of interest, as reported below. We will also collect data on subgroups of sex, age, race, pulmonary function test, eosinophil counts, Quality of life scores, and frequency of exacerbations.
Main outcome(s)
Main outcome(s)
We will extract data for a pooled analysis on the following outcomes: (1) Pneumonia (Lower respiratory tract infection); (2) Bronchitis; (3) Nasopharyngitis; (4) Upper Respiratory Tract Infections; (5) Other non-respiratory infectious adverse events

Measures of effect: Hazards ratio, and Odds ratio
Study Records
Study Records
All protocol amendments, data extraction updates, and decisions regarding inclusion/exclusion will be logged in a version-controlled document to ensure auditability. The review will be conducted in accordance with the PRISMA and MOOSE guidelines for systematic reviews and meta-analyses.


Data Management
Data Management
All data related to this systematic review and meta-analysis will be collected, managed, and stored in accordance with established methodological guidelines and principles of transparency and reproducibility. All extracted data will be stored securely in password-protected Excel spreadsheets. Only authorized members of the review team will have access to the data files. Regular backups will be created to prevent data loss.
Selection Process
Selection Process
Titles and abstracts identified through the search strategy will be screened independently by two reviewers (FR and TT). Discrepancies between reviewers will be resolved through adjudication by a third, independent reviewer (ESN)
Data Collection process
Data Collection process
Data Extraction
Data on each of the outcomes described will be collected. Data will be extracted independently by two team members. If further information is required, authors from the original article will be contacted to obtain data not available in published reports.
A standardized data extraction form will be developed and pilot tested. The following data will be extracted from each included study:
  • Study Characteristics: First author, publication year, country, study design, trial registration (if applicable), funding sources, and conflict of interest disclosures.
  • Participant Characteristics: Sample size, mean age, gender distribution, baseline asthma severity, inclusion/exclusion criteria.
  • Intervention Details: Dose, duration, and route of Tezepelumab administration; co-interventions; standard therapy components.
  • Outcomes: Type and number of adverse events (including total AEs and specific types like infections), definitions used, follow-up duration, and method of adverse event reporting.
 In addition, the following baseline characteristics will be collected: (1) race distribution; (2) proportion of patients with severe persistent asthma with eosinophilia; (3) proportion of patients with severe persistent asthma without eosinophilia; (4) Quality of life scores; (5) comorbidities; and (6) follow-up in months. The data will be extracted and recorded on an Excel template by two authors: FR and TT.
Risk of Bias Assessment
Risk of Bias Assessment
We will use the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials for quality assessment of individual randomized studies.
Strategy for data synthesis
Strategy for data synthesis
The systematic review and meta-analysis will be performed in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines.
A meta-analysis will be performed if ≥2 studies report the same outcome (e.g., adverse events or infections) in a comparable way.
We will extract the data from individual studies using hazard ratios (HR) to preserve time-to-event data from individual studies. Effects for binary endpoints ((e.g., incidence of adverse events, infections)  will be compared using pooled HR or odds-ratios (OR) with 95% confidence intervals. Weighted mean differences will be used to pool continuous outcomes. Heterogeneity will be evaluated with Cochran Q test and I² statistics; p values inferior to 0.10 and I²>25% will be considered significant for heterogeneity. The decision to use either a random-effect or fixed-effect model will be made after a critical appraisal of all included studies. Review Manager 5.4 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) will be used for statistical analysis
Analysis of subgroups or subsets
Analysis of subgroups or subsets
We will extract data and perform sub-analyses in the following subgroups: (1) male; (2) female; (3) age ≥65 years old; (4) age <65 years old; (5) by duration of follow up (less than 6 months and greater than 6 months); (7)  By type of adverse event (e.g: infections vs general Adverse events)
Meta-bias Assessment
Meta-bias Assessment
If ≥10 studies are included in a meta-analysis, publication bias will be assessed via:
  • Visual inspection of funnel plots
  • Egger’s regression test for small-study effects
Keywords
Keywords
Severe Asthma
Tezepelumab
Adverse drug reactions

Language
Language
English
Conflicts of Interest
Conflicts of Interest
None
Funding
Funding
None
Protocol references
Qin J, Wang G, Han D. Long-term safety of tezepelumab in patients with asthma: a systematic review and meta-analysis of randomized controlled trials. J Asthma. 2025 Jan;62(1):4-13. doi: 10.1080/02770903.2024.2385973. Epub 2024 Aug 2. PMID: 39067012.

Shaban Abdelgalil M, Ahmed Elrashedy A, Awad AK, Reda Gad E, Ali MM, Abdelmoez Farahat R, Hassan Shawki B, Abd-ElGawad M. Safety and efficacy of tezepelumab vs. placebo in adult patients with severe uncontrolled asthma: a systematic review and meta-analysis. Sci Rep. 2022 Dec 3;12(1):20905. doi: 10.1038/s41598-022-24763-9. PMID: 36463281; PMCID: PMC9719466.

Diver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, Johnston J, Molfino N, Parnes JR, Megally A, Colice G, Brightling CE; CASCADE study investigators. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021 Nov;9(11):1299-1312. doi: 10.1016/S2213-2600(21)00226-5. Epub 2021 Jul 10. Erratum in: Lancet Respir Med. 2021 Nov;9(11):e106. doi: 10.1016/S2213-2600(21)00446-X. PMID: 34256031.

Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, Hellqvist Å, Bowen K, Kaur P, Almqvist G, Ponnarambil S, Colice G. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13;384(19):1800-1809. doi: 10.1056/NEJMoa2034975. PMID: 33979488.

Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017 Sep 7;377(10):936-946. doi: 10.1056/NEJMoa1704064. Erratum in: N Engl J Med. 2019 May 23;380(21):2082. doi: 10.1056/NEJMx180026. PMID: 28877011.

Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, Griffiths JM, Sałapa K, Hellqvist Å, Almqvist G, Lal H, Kaur P, Skärby T, Colice G; SOURCE study group. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022 Jul;10(7):650-660. doi: 10.1016/S2213-2600(21)00537-3. Epub 2022 Mar 29. Erratum in: Lancet Respir Med. 2022 Jul;10(7):e72. doi: 10.1016/S2213-2600(22)00128-X. PMID: 35364018.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71.