Contributions
Abstract: 88
Type: Scientific Session
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Long-term safety data, including mortality rates, in large real-world cohorts of multiple sclerosis (MS) patients treated with anti-CD20 drugs are limited.
Objective/Aims: To assess mortality rates in MS patients treated with rituximab (RTX-MS) and to determine whether deaths were due to infusion reactions or other potential RTX-related complications.
Methods: Causes and date of death among RTX-MS patients in Kaiser Permanente Southern California (KPSC) 2008-2017 were identified from complete electronic health records (through 12/31/2017) and state death certificate records (through 12/31/2016). 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 02/28/2018, causes of death through 12/31/2016). Deaths occurring within 2 weeks of the last RTX infusion were considered infusion-related unless clearly attributable to suicide or trauma.
Results: We identified 1246 and 1225 RTX-MS patients with 2689.4 and 3264.2 person-years of follow-up in KPSC and COMBAT-MS cohorts, respectively. The mean age at first RTX dose was 44.6/39.3 years and 71/71% were female. Most patients received 1000 mg first-dose and 500 mg for subsequent infusions. Fifteen deaths were identified in KPSC and 2 in COMBAT-MS, none occurred within 2 weeks of the last RTX infusion. Crude mortality rates were 5.6 and 0.61 per 1000 person-years, respectively. In KPSC cause of death was as follows: suicide (n=2); complications of MS-related disability (n=6, fall, aspiration pneumonia, pulmonary embolism); cardiovascular (CV) disease (n=3, time since last RTX dose 1.6, 2.9, and 5.5 months), sudden death with CV risk factors (n=3, last RTX dose 1.5, 20.8 and 28.7months) and unknown (n=1, last RTX dose 3.3 months). In COMBAT-MS, causes of death were suicide and unknown, both occurred ~6 months after last RTX dose.
Conclusions: Crude all-cause mortality rates in RTX-MS patients are somewhat lower than published MS rates in both study cohorts. We found no infusion-related deaths, 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 RTX used in cancer patients. These findings provide a basis for comparative safety studies across different CD20 therapies and dosing regimens. Updated data and age/sex-adjusted mortality rates will be presented.
Disclosure: This work is supported by a Patient-Centered Outcomes Research Institute Award (PCORI MS-1511-33196). Jessica Smith and Thomas Frisell have nothing to disclose.
Annette Langer-Gould: Served as site-PI for two industry-sponsored RCTs (Roche, Biogen Idec).
Fredrik Piehl: Has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and on behalf of FP his Department has received travel support and/or compensation for lectures from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva, which have been used exclusively for the support of research activities.
Abstract: 88
Type: Scientific Session
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Long-term safety data, including mortality rates, in large real-world cohorts of multiple sclerosis (MS) patients treated with anti-CD20 drugs are limited.
Objective/Aims: To assess mortality rates in MS patients treated with rituximab (RTX-MS) and to determine whether deaths were due to infusion reactions or other potential RTX-related complications.
Methods: Causes and date of death among RTX-MS patients in Kaiser Permanente Southern California (KPSC) 2008-2017 were identified from complete electronic health records (through 12/31/2017) and state death certificate records (through 12/31/2016). 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 02/28/2018, causes of death through 12/31/2016). Deaths occurring within 2 weeks of the last RTX infusion were considered infusion-related unless clearly attributable to suicide or trauma.
Results: We identified 1246 and 1225 RTX-MS patients with 2689.4 and 3264.2 person-years of follow-up in KPSC and COMBAT-MS cohorts, respectively. The mean age at first RTX dose was 44.6/39.3 years and 71/71% were female. Most patients received 1000 mg first-dose and 500 mg for subsequent infusions. Fifteen deaths were identified in KPSC and 2 in COMBAT-MS, none occurred within 2 weeks of the last RTX infusion. Crude mortality rates were 5.6 and 0.61 per 1000 person-years, respectively. In KPSC cause of death was as follows: suicide (n=2); complications of MS-related disability (n=6, fall, aspiration pneumonia, pulmonary embolism); cardiovascular (CV) disease (n=3, time since last RTX dose 1.6, 2.9, and 5.5 months), sudden death with CV risk factors (n=3, last RTX dose 1.5, 20.8 and 28.7months) and unknown (n=1, last RTX dose 3.3 months). In COMBAT-MS, causes of death were suicide and unknown, both occurred ~6 months after last RTX dose.
Conclusions: Crude all-cause mortality rates in RTX-MS patients are somewhat lower than published MS rates in both study cohorts. We found no infusion-related deaths, 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 RTX used in cancer patients. These findings provide a basis for comparative safety studies across different CD20 therapies and dosing regimens. Updated data and age/sex-adjusted mortality rates will be presented.
Disclosure: This work is supported by a Patient-Centered Outcomes Research Institute Award (PCORI MS-1511-33196). Jessica Smith and Thomas Frisell have nothing to disclose.
Annette Langer-Gould: Served as site-PI for two industry-sponsored RCTs (Roche, Biogen Idec).
Fredrik Piehl: Has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and on behalf of FP his Department has received travel support and/or compensation for lectures from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva, which have been used exclusively for the support of research activities.