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Disease-modifying treatments for multiple sclerosis have not affected the incidence of neoplasms in clinical trials over 3 decades: a meta-analysis with meta-regression

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Abstract

Objective

Our study aimed to estimate the incidence of neoplasms in clinical trials of DMTs for MS and to test the hypothesis that DMTs increase the risk of neoplasms in the duration of MS randomized controlled trials (RCTs).

Methods

Data were extracted from 42 RCTs of DMTs published between 1991 and 2020. The incidence rate (IR) of neoplasms was estimated by pooling the neoplasms in the active and placebo-treatment arm per patient-year. The neoplasm incidence rate ratio (IRR) of active over placebo-treatment arms was used as measure of the effect of DMTs on the risk of developing neoplasms.

Results

The meta-analysis included 10,638 placebo and 16,360 active-treatment arm patients. A non-significant pooled neoplasm incidence rate ratio (IRR: 1.0797; 95% CI: 0.8281 to 1.4077; P = 0.5711) with no heterogeneity (I2 = 0%) was observed in active over placebo-treatment groups from 1991 to 2020. We found a significant association between the incidence of neoplasms and the year of publication in both active and placebo arms of RCTs. Trials of sequestrating and depletive DMTs were associated with significantly higher incidence of neoplasms in both active and placebo-treated arms compared to immunomodulatory treatment trials.

Conclusions

Our study indicates that treatment with DMTs has not modified the risk of neoplasms in MS clinical trials from 1991 to 2020, which may reflect a low carcinogenic potential of DMTs and/or that the neoplasia latencies far exceed the typical MS trial observation periods.

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Funding

No funding source had any role in design, conduct of study, collation, analysis, interpretation of data or in the preparation, review, approval, or decision to submit the manuscript.

Author information

Authors and Affiliations

  1. School of Medicine, European University Cyprus, Nicosia, 2404, Cyprus

    Dimitrios Papadopoulos

  2. Salpetriere Neuropsychiatric Clinic, Metamorphosi, 14452, Greece

    Dimitrios Papadopoulos

  3. Department of Neurology, KAT General Hospital of Attica, Athens, 14561, Greece

    Panagiotis Gklinos

  4. ASTAT- Statistics in Clinical Research, Athens, 16675, Greece

    Giorgos Psarros & Eumorphia Maria Delicha

  5. Department of Neurology, Korgialenio-Benakio “Hellenic Red Cross” General Hospital, Athens, 11526, Greece

    Konstantina Drellia

  6. Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany

    Tim Friede

  7. 1St Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11528, Greece

    Dimos D. Mitsikostas

  8. Department of Cellular and Molecular Neuroscience, Imperial College London, London, W12 0NN, UK

    Richard S. Nicholas

  9. UCL Institute of Ophthalmology, London, EC1V 9RL, UK

    Richard S. Nicholas

  10. Population Data Science, Swansea University Medical School, Swansea, SA2 8PP, UK

    Richard S. Nicholas

Authors
  1. Dimitrios Papadopoulos
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  7. Dimos D. Mitsikostas
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Contributions

Concept and design: DP. Acquisition, analysis or interpretation of data: PG, KD, DP. Drafting of the manuscript: PG, DP. RN. Critical revision of manuscript for important intellectual content: DM, TF, RN. Statistical analysis: GP, ED, TF. Administrative technical or material support: PG, KD Supervision: DP, DM, RN.

Corresponding author

Correspondence to Dimitrios Papadopoulos.

Ethics declarations

Conflicts of interest

Dr. D Papadopoulos has received consulting, speaking fees, and travel grants from Bayer, Genesis Pharma, Merck, Mylan, Novartis, Roche, Sanofi-Aventis, Specifar, and Teva. Dr. P Gklinos has nothing to disclose. Dr. K Drellia has nothing to disclose. Mr. G Psarros has nothing to disclose. Dr. E Delicha has nothing to disclose. Prof. DD Mitsikostas has received consulting, speaking fees, and travel grants from Allergan, Amgen, Bayer, Biogen, Cefaly, Genesis Pharma, GlaxoSmithKline, ElectroCore, Eli Lilly, Merck-Serono, Merz, Mylan, Novartis, Roche, Sanofi-Genzyme, Specifar, and Teva. Prof R Nicholas has received consulting and speaking fees from Novartis, Roche, and Biogen.

Ethical standards

No ethics approval or patient consent was obtained because all data used in this study were collected from previously published peer-reviewed articles.

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Papadopoulos, D., Gklinos, P., Psarros, G. et al. Disease-modifying treatments for multiple sclerosis have not affected the incidence of neoplasms in clinical trials over 3 decades: a meta-analysis with meta-regression. J Neurol 269, 3226–3237 (2022). https://doi.org/10.1007/s00415-021-10932-9

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  • DOI: https://doi.org/10.1007/s00415-021-10932-9

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