Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies

Ferrán Catalá-López^{1

2

3}, Laura Tejedor-Romero⁴, Jane A Driver^{5

6

7}, Brian Hutton^{8

9}, Joan Vicent Sánchez-Ortí^{10

11}, Manuel Ridao^{12

13

14}, Adolfo Alonso-Arroyo^{15

16}, Patricia Correa-Ghisays^{10

11}, Jaume Forés-Martos^{10

17}, Vicent Balanzá-Martínez^{10

11}, Alfonso Valencia^{18

19}, Inmaculada Cobos¹⁷, Rafael Tabarés-Seisdedos^{20

21}

Affiliations

¹ Centre for Human and Social Sciences (CCHS), Institute of Public Goods and Policies (IPP), Spanish National Research Council (CSIC), Madrid, Spain. ferran_catala@outlook.com.
² Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain. ferran_catala@outlook.com.
³ Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada. ferran_catala@outlook.com.
⁴ Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Medicines and Healthcare Products Agency (AEMPS), Madrid, Spain.
⁵ Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA, USA.
⁶ Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain.
¹¹ Department of Medicine, University of Valencia/INCLIVA Health Research Institute, Valencia, Spain.
¹² Institute for Health Research in Aragon (IISA), Zaragoza, Spain.
¹³ Data Science for Health Services and Policy Research, Aragon Health Sciences Institute (IACS), Zaragoza, Spain.
¹⁴ Research Network on Chronicity, Primary Care, and Health Promotion (RICAPPS), Institute of Health Carlos III, Madrid, Spain.
¹⁵ Department of Pathology, Stanford University, California, USA.
¹⁶ Information and Social and Health Research (UISYS) Joint Research Unit, Spanish National Research Council (CSIC), University of Valencia, Valencia, Spain.
¹⁷ Department of History of Science and Documentation, University of Valencia, Valencia, Spain.
¹⁸ Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
¹⁹ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
²⁰ Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain. rafael.tabares@uv.es.
²¹ Department of Medicine, University of Valencia/INCLIVA Health Research Institute, Valencia, Spain. rafael.tabares@uv.es.

PMID: 39425150
PMCID: PMC11487888
DOI: 10.1186/s13643-024-02677-z

Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies

Ferrán Catalá-López et al. Syst Rev. 2024.

. 2024 Oct 18;13(1):263.

doi: 10.1186/s13643-024-02677-z.

Authors

Affiliations

¹ Centre for Human and Social Sciences (CCHS), Institute of Public Goods and Policies (IPP), Spanish National Research Council (CSIC), Madrid, Spain. ferran_catala@outlook.com.
² Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain. ferran_catala@outlook.com.
³ Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada. ferran_catala@outlook.com.
⁴ Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Medicines and Healthcare Products Agency (AEMPS), Madrid, Spain.
⁵ Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA, USA.
⁶ Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain.
¹¹ Department of Medicine, University of Valencia/INCLIVA Health Research Institute, Valencia, Spain.
¹² Institute for Health Research in Aragon (IISA), Zaragoza, Spain.
¹³ Data Science for Health Services and Policy Research, Aragon Health Sciences Institute (IACS), Zaragoza, Spain.
¹⁴ Research Network on Chronicity, Primary Care, and Health Promotion (RICAPPS), Institute of Health Carlos III, Madrid, Spain.
¹⁵ Department of Pathology, Stanford University, California, USA.
¹⁶ Information and Social and Health Research (UISYS) Joint Research Unit, Spanish National Research Council (CSIC), University of Valencia, Valencia, Spain.
¹⁷ Department of History of Science and Documentation, University of Valencia, Valencia, Spain.
¹⁸ Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
¹⁹ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
²⁰ Centre for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain. rafael.tabares@uv.es.
²¹ Department of Medicine, University of Valencia/INCLIVA Health Research Institute, Valencia, Spain. rafael.tabares@uv.es.

PMID: 39425150
PMCID: PMC11487888
DOI: 10.1186/s13643-024-02677-z

Abstract

Background: The association between cancer and multiple sclerosis has long been investigated. Several studies and reviews have examined the risk of cancer among patients with multiple sclerosis treated with disease-modifying therapies (DMTs) but with conflicting results. This study will aim to investigate the association between DMTs for multiple sclerosis and subsequent cancer risk using research synthesis methods.

Methods/design: We designed and registered a study protocol for a systematic review and meta-analysis. We will include randomised and non-randomised trials, prospective or retrospective cohort studies, and case-control studies of treatment with DMTs compared with placebo, no treatment, or another active agent. The primary outcome will be the risk of cancer (all-malignant neoplasms) in association with the exposure of DMTs. Secondary outcomes will include site-specific cancers (e.g. breast cancer). Literature searches will be conducted in multiple electronic databases (from their inception onwards), including the following: PubMed/MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Two researchers will screen all citations, full-text articles, and abstract data independently. The risk of bias (quality) of individual studies will be appraised using an appropriate tool. If feasible, we will use a two-stage approach to evidence synthesis: (1) Peto's method for meta-analysis of data from randomised trials alone; and (2) Random-effects model for meta-analysis adding data from non-randomised studies. We will calculate odds ratios and their associated 95% confidence intervals. Potential sources of heterogeneity will be explored in additional analyses (e.g. subgroups considering different DMTs individually, mechanism of action, type of control, length of follow-up, mode of treatment).

Discussion: This systematic review and meta-analysis of randomised and non-randomised studies will provide an updated synthesis of the risk of cancer associated with DMTs for adult patients with multiple sclerosis. This study will also examine some factors that may explain potential variations across studies. The findings will be published in a peer-reviewed journal.

Systematic review registration: Open Science Framework ( https://osf.io/v4sez ).

Keywords: Cancer; Disease-modifying therapy; Meta-analysis; Multiple sclerosis; Systematic review.

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Conflict of interest statement

The authors declare that they have no competing interests.

References

1. Jakimovski D, Bittner S, Zivadinov R, Morrow SA, Benedict RH, Zipp F, et al. Multiple sclerosis. Lancet. 2024;403(10422):183–202. 10.1016/S0140-6736(23)01473-3. - PubMed
1. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA. 2021;325(8):765–79. 10.1001/jama.2020.26858. PMID: 33620411. - PubMed
1. GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024 Mar 5:S1474–4422(24)00038–3. 10.1016/S1474-4422(24)00038-3. PMID: 38493795. - PMC - PubMed
1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222. 10.1016/S0140-6736(20)30925-9. - PMC - PubMed
1. Multiple sclerosis in adults: management (NICE Guideline, No. 220). London: National Institute for Health and Care Excellence (NICE); 2022. Available at: https://www.nice.org.uk/guidance/ng220 (accessed March 19, 2024).

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Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies

Affiliations

Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical