#ECTRIMS2018 – Lower Mortality Rate in US, Sweden for MS Patients Treated With Rituximab, Study Reports

Jose Marques Lopes, PhD avatar

by Jose Marques Lopes, PhD |

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Treatment of multiple sclerosis (MS) patients with rituximab leads to lower-than-reported mortality rates, according to a large real-world study in the U.S. and Sweden.

The findings also revealed no deaths due to infusion reactions or to systemic inflammation.

The study, “Mortality rates in large US and Swedish rituximab-treated multiple sclerosis cohorts,” was presented at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place Oct. 10-12 in Berlin, Germany. The presenter was Annette Langer-Gould, MD, PhD, from Kaiser Permanente.

Rituximab is sold under the brand name Rituxan as a treatment for different disorders and some types of cancer, including lymphoma. The therapy, developed by Genentech and Biogen, is used off-label in MS patients.

Rituximab targets a protein called CD20 in the antibody-producing immune B-cells, causing their depletion. B-cells are known to be involved in MS development.

Recent research from Sweden showed that MS patients receiving rituximab as first-line therapy stay on it longer than other disease-modifying drugs, and have fewer relapses and less new brain lesions. Also, off-label — outside the approved indications — use of rituximab for MS and other disorders is well-tolerated, safe, and leads to complete B-dell depletion.

Despite these benefits, long-term safety data of anti-CD20 medications, including mortality rates, in large real-world groups of MS patients are limited.

Aiming to address this gap, scientists from the U.S. and Sweden evaluated mortality rates in rituximab-treated MS patients and analyzed if deaths were due to infusion reactions or other potential treatment-related complications.

Information on causes and date of death among patients in the health maintenance organization Kaiser Permanente Southern California (KPSC) was collected from 2008 to 2017. In turn, the COMBAT-MS group, a validated subset of the Swedish MS Register, was linked with the country’s causes-of-death registry, with date of death analyzed through 2018 and causes of death through 2016.

The team considered that deaths occurring within two weeks of the last rituximab infusion were infusion-related, unless clearly attributable to suicide or trauma.

A total of 1,246 and 1,225 rituximab-treated MS patients with 2,689.4 and 3,264.2 person-years (a measure that sums actual follow-up duration in each patient, and is higher with greater number of years in study) were identified in the U.S. and Swedish groups, respectively. Both groups had 71% women, and the mean age at rituximab treatment start was 44.6 and 39.3 years, respectively.

Most patients were treated with 1,000 mg in the first-dose, and 500 mg in subsequent infusions.

All-cause mortality rates were 4.75 and 0.61 per 1,000 person-years in the U.S. and Swedish groups, respectively, which were “somewhat lower than published rates, likely due to patient selection,” Longer-Gould said. The higher rate seen in the U.S. might be linked to the fact that this group was older and “sicker,” according to the research.

Fifteen deaths were identified in KPSC U.S. group and two in the Swedish COMBAT-MS group, but none within two weeks of the last rituximab dose.

In the KPSC group, the team found two cases of suicide, six deaths due to complications of MS-related disability — fall, aspiration pneumonia, and pulmonary embolism (blockage of pulmonary artery). Three deaths were caused by cardiovascular disease, three others by sudden death with cardiovascular risk factors, and one patient with unknown cause of death (last treated 3.3 months before death).

In Sweden’s COMBAT-MS group, the team found one case of suicide and another with unknown cause of death, both six months after the last treatment.

Of note, the team found no infusion-related deaths, neither due to a systemic inflammatory response. They also noted the absence of deaths suspicious for Kounis syndrome — acute coronary syndrome caused by an allergic reaction or a strong immune reaction — as has been reported with Ocrevus (ocrelizumab, marketed by Genentech), and with high-dose Rituxan in cancer patients.

Overall, “these findings provide a basis for comparative safety studies across different CD20 therapies and dosing regimens,” the investigators wrote. Ocrevus also is a CD20-targeting therapy.

Of note, one of the study authors was a principal investigator in a clinical trial sponsored by Roche, which owns Genentech, and Biogen, while another received travel support and/or compensation for lectures from those companies.

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