BERLIN—Crude all-cause mortality rates among patients with multiple sclerosis (MS) who were treated with rituximab were lower than published MS rates in two large study cohorts, according to a report presented at ECTRIMS 2018. “We found no infusion-related deaths and no deaths due to systemic inflammatory response syndrome or otherwise suspicious for Kounis syndrome, as has been reported with ocrelizumab and with high-dose regimens of rituximab used in cancer patients,” said Annette Langer-Gould, MD, PhD, and colleagues. “These findings provide a basis for comparative safety studies across different CD20 therapies and dosing regimens,” said Dr. Langer-Gould, who is Regional Lead for Clinical and Translational Neuroscience for the Southern California Permanente Medical Group in Pasadena.
Long-term safety data, including mortality rates, in large real-world cohorts of patients with MS treated with anti-CD20 drugs are limited. Dr. Langer-Gould and colleagues assessed mortality rates in patients with MS who were treated with rituximab to determine whether deaths were due to infusion reactions or other potential rituximab-related complications.
Causes and date of death among patients with MS who were treated with rituximab in Kaiser Permanente Southern California (KPSC) during the years 2008 to 2017 were identified from complete electronic health records (through December 31, 2017) and state death certificate records (through December 31, 2016). The Comparison Between All MS Therapies (COMBAT-MS) cohort, a chart-validated subset of the Swedish MS Register, was linked with the national causes-of-death registry (date of death through February 28, 2018; causes of death through December 31, 2016). Deaths occurring within two weeks of the last rituximab infusion were considered infusion-related unless clearly attributable to suicide or trauma.
The researchers identified 1,246 and 1,225 rituximab-treated patients with 2,689.4 and 3,264.2 person-years of follow-up in the KPSC and COMBAT-MS cohorts, respectively. The mean age at first rituximab dose was 44.6 and 39.3, respectively, and in both cohorts 71% were female. Most patients received 1,000 mg for their first-dose and 500 mg for subsequent infusions. Fifteen deaths were identified in KPSC, and two deaths were identified in COMBAT-MS; none occurred within two weeks of the last rituximab infusion. Crude mortality rates were 5.6 and 0.61 per 1,000 person-years, respectively. In KPSC, causes of death were as follows: suicide (n = 2), complications of MS-related disability (n = 6; eg, fall, aspiration pneumonia, and pulmonary embolism), cardiovascular disease (n = 3; time since last rituximab dose, 1.6, 2.9, and 5.5 months), sudden death with cardiovascular risk factors (n = 3; last rituximab dose, 1.5, 20.8, and 28.7 months) and unknown (n = 1; last rituximab dose, 3.3 months). In COMBAT-MS, causes of death were suicide and unknown, and both deaths occurred approximately six months after the last rituximab dose.
This study was supported by a Patient-Centered Outcomes Research Institute Award (PCORI MS-1511-33196).