Cancer Risk and Disease Modifying Therapies in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disorder characterised by inflammatory demyelination and neurodegeneration in the central nervous system. Over the past two decades, an expanding repertoire of disease-modifying therapies (DMTs) has transformed MS management by modulating innate and adaptive immune responses. While these agents reduce relapse rates and delay disability progression, they may also influence the immune system’s capacity for cancer immunosurveillance. Epidemiological studies have reported both increased and decreased risks of various cancers in MS populations, with variation by age, sex, treatment history and regional screening practices. Some DMTs carry immunosuppressive properties that could permit neoplastic proliferation, whereas others may exert anti-tumour activity indirectly. Clinical decision making requires balancing the long-term benefits of immune modulation against potential oncogenic risks, particularly in older patients or those with prior malignancy. Emerging computational and cohort studies underscore the interplay between inflammaging, immunosenescence and neoplasm development, suggesting that patient-specific factors such as smoking, sex and age at MS onset further modulate cancer risk. There remains an urgent need for harmonised surveillance guidelines and personalized treatment algorithms to optimise safety and efficacy globally.

Research from Nature Portfolio

A large observational cohort from Southern Spain examined the frequency of neoplasm development in 250 MS outpatients over nearly four decades of clinical care. Neoplasm prevalence was 24%, with a cancer prevalence of 6.8%—in line with expected rates in MS cohorts. Skin tumours predominated, but solid organ malignancies were also represented. Multivariable survival analyses identified smoking, female sex and older age at MS diagnosis as independent risk factors for neoplasm development, while a secondary progressive phenotype and longer exposure to interferon-β emerged as protective factors. Interaction models revealed that the combined effect of smoking and older age markedly increased cancer risk. These findings highlight the importance of integrating baseline demographic characteristics and treatment duration into risk stratification when prescribing DMTs.

Cancer Risk and Disease Modifying Therapies in Multiple Sclerosis publication trend

The graph below shows the total number of articles in cancer risk and disease modifying therapies in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Multiple sclerosis (MS): A chronic immune-mediated disorder of the central nervous system marked by demyelination and neurodegeneration.

Disease-modifying therapies (DMTs): Treatments that alter the natural course of MS by modulating or suppressing the immune response.

Neoplasm: An abnormal cellular growth or tumour, benign or malignant.

Immunosurveillance: The immune system’s process of detecting and eliminating emerging malignant cells.

Inflammaging: Chronic, low-grade inflammation associated with ageing that contributes to disease risk.

Immunosenescence: Age-related decline in immune function affecting resistance to infections and cancer.

Standardized incidence ratio (SIR): The ratio of observed to expected cancer cases in a study population.

Hazard ratio (HR): A measure comparing the hazard rates of events between two groups over time.

Pan-cancer analysis: A comparative study across multiple cancer types to identify common molecular or clinical features.

References

1. Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies. Frontiers in Immunology (2020).
2. Potential risk of disease modifying therapies on neoplasm development and coadjutant factors in multiple sclerosis outpatients. Scientific Reports (2021).
3. Incidence of cancer in multiple sclerosis before and after the treatment era– a registry- based cohort study. Multiple Sclerosis and Related Disorders (2021).
4. Identification of crucial inflammaging related risk factors in multiple sclerosis. Frontiers in Molecular Neuroscience (2024).
5. Multiple sclerosis and breast cancer risk: a meta-analysis of observational and Mendelian randomization studies. Frontiers in Neuroinformatics (2023).