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No Elevated Cancer Risk With MS Therapies in COMBAT-MS Data

Study examines incidence of cancer in patients taking rituximab, fingolimod, and natalizumab.


BERLINThe risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.

Those findings from the Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53–2.10), said Peter Alping, a PhD student in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm.

Surveillance for Risk of Malignancy

Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers,” he said.

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.

They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.

Comparing Incidence Rates

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of cancer.

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