The big-D (DMTs) instead of the big-C.

T

First the symptoms, then the diagnosis, then the therapy discussion. Clinicians and patients with MS are constantly facing dilemmas and challenges with a dose of fear. Common questions that concern the DMTs are: Could these drugs be as harmful as efficient? Given that these drugs affect the immune system in various ways, could severe adverse events such as cancer occur?

Our recent analysis provided evidence that the differential risk of reporting cancer outcomes among various DMTs is the more or less the same. The database that we used to reach this conclusion was the FAERS of the United States (Food and Drug Administration Adverse Events Reporting System). This database includes real-life spontaneous adverse events reports from all over the world (but mainly from the US). We considered all the registered adverse event reports from the DMTs: Interferons (Avonex®/ Rebif®/ Plegridy®/ Extavia®), Glatiramer acetate (Copaxone®/ Glatopa®), Natalizumab (Tysabri®), Fingolimod (Gilenya®), Teriflunomide (Aubagio®), Dimethyl Fumarate (Tecfidera®), Alemtuzumab (Lemtrada®), Ocrelizumab (Ocrevus®), Siponimod (Mayzent®), Cladribine (Mavenclad®),  (more than 150.000 cleaned reports with unique case ID), and we performed a disproportionality analysis (pharmacovigilance study). Our study aimed to detect all the possible cancer outcomes and to examine if any of the drugs had an increased, disproportionate signal of cancer reporting (which could be translated to a cancer safety signal).

The outcome categories that we examined were cancer outcomes in total, haematological tumours, and solid tumours. Moreover, three sensitivity analyses were performed to increase the robustness of our results. In one of them, Alemtuzumab and Interferons showed an increased signal of disproportionate reporting. However, as we discuss in our paper, the increased reporting of Interferons can be justified and probably is not translated to an actual safety signal. The results need to be verified but are promising and show that DMTs (also highly-active DMTs) do not increase the frequency of cancer reporting in FAERS. The full article with details about this topic and our analysis is available online in the British Journal of Clinical Pharmacology.

Stamatellos VP, Siafis S, Papazisis G. Disease-modifying agents for multiple sclerosis and the risk for reporting cancer: A disproportionality analysis using the US Food and Drug Administration Adverse Event Reporting System database. Br J Clin Pharmacol. 2021 May 16. doi: 10.1111/bcp.14916. Epub ahead of print. PMID: 33998034.

Disclosures: The author of this post and the article’s authors mentioned above have no actual or potential conflict of interest concerning this topic.

About me: My name is Vasileios-Periklis Stamatellos. I was born and raised in Thessaloniki, Greece, where I studied Medicine (Aristotle University of Thessaloniki). Afterwards, I acquired the Master of Science (MSc) degree in Medical Research Methodology from the same University. I currently live in Berlin, where I work as a resident doctor in an outpatient clinic for Neurology-Psychiatry-Child psychiatry.

I look forward to continuing the Neurology residency in a hospital and simultaneously conducting clinical research in Neurology. In my free time, I enjoy walking in the green parks of Berlin, playing and watching Basketball, and petting my cat.

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5 comments

  • Fingolimod

    “What this tells us is that ceramides need to be carefully controlled in a cancer setting,” said Ogretmen. This is particularly important because there are several FDA-approved drugs, such as FTY720 for multiple sclerosis, that increase ceramide signaling. Systemic increase of ceramide signaling in cancer patients may be harmful because it weakens the anti-cancer function of the patient’s immune system, he said

    https://medicalxpress.com/news/2021-06-aging-impairs-anti-tumor-t-cell-response.html

    Level of concern^?

    • We discuss S1P receptor modulation in our article. Don’t forget that the study is a pharmacovigilance study and has limitations. For these reason the results of our study are promising but stronger evidence is needed to prove it.

    • I don’t know him in person but I know his work in Autologous Hematopoietic Stem Cell Transplantation for MS patients. He was one of the first to introduce this type of therapy(1985).

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