Contributions
Abstract: P1229
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: TYGRIS was a 5-year observational cohort study designed to obtain long-term safety data in natalizumab-treated MS patients in clinical practice.
Objectives: To examine the incidence and pattern of serious adverse events (SAEs) in a large postmarketing sample of natalizumab-treated MS patients.
Methods: Investigators monitored natalizumab-treated patients and reported SAEs occurring during the study. Malignancy incidence rates were compared with rates in the Surveillance, Epidemiology and End Results and Globocan databases.
Results: Of 6508 enrolled patients (US, 2207; rest of world, 4301), 4938 (76%) completed the 5-year study. At enrollment, mean (SD) age was 40.1 (10.44) years, and 91% of patients had prior immunomodulatory/immunosuppressant use. Patients received a median (range) of 44 (0-77) natalizumab doses before/during the study, accruing ≈21,795 patient-years of natalizumab exposure. Of 6434 dosed patients, 987 (15%) experienced ≥1 treatment-emergent (TE) SAE, 222 (3%) reported ≥1 TE SAE leading to natalizumab discontinuation, and no individual SAE occurred in ≥1% of patients. SAEs occurring in >0.5% of patients included urinary tract infection (0.8%), pneumonia (0.7%), progressive multifocal leukoencephalopathy (PML; 0.7%), and immune reconstitution inflammatory syndrome (0.6%). Fifty-five patients (< 1%) experienced ≥1 TE serious opportunistic infection, 44 of which were PML. Most PML cases (42/44) occurred after >24 infusions; 23 cases were anti-JCV antibody positive ≥6 months pre-diagnosis; serostatus ≥6 months prior to PML development was unknown or not reported in 21 cases. Two patients with PML had fatal outcomes. The malignancy incidence rate (449.0 per 100,000 patient-years [95% CI: 375.1-533.1]) was similar to rates in the general population (460.2 and 519.2 per 100,000 person-years); no trends between dosing and malignancy incidence were observed. Six subjects experienced hepatotoxic events, including cytolytic hepatitis (n=2), liver injury (n=2), toxic hepatitis (n=1), and hepatocellular injury (n=1); most cases had clear evidence of alternative cause or ≥1 confounder. Of 96 fatal events in 77 patients, most (91/96) were considered unlikely/not related to study drug or causality was not reported.
Conclusion: The nature, character, and rate of SAEs reported in this study of long-term safety data from natalizumab-treated patients in real-word settings are consistent with the drug"s known safety profile.
Disclosure: Supported by Biogen.
JF: received personal compensation for consulting, speaking, and scientific advisory boards from Biogen, Genzyme, Teva; received financial support for research activities from Biogen, Genentech-Roche, Genzyme, Teva.
CCI, MW, KE, BH, DS, PRH, LL, GB: employees of and may hold stock and/or stock options in Biogen.
NL, JS: contractors for Biogen.
PV: has received honoraria and consulting fees from Almirall, Bayer, Biogen, GSK, Merck-Serono, Novartis, Sanofi-Genzyme, Teva; has received research support from Bayer, Biogen, Merck-Serono, Sanofi-Genzyme.
MH: served on a medical advisory board for Biogen; serves on the editorial board of the Multiple Sclerosis Journal, has received speaker"s honoraria from Bayer-Schering, Biogen, Novartis; receives research support from Dystonia Ireland, the European Dystonia Foundation, the Health Research Board of Ireland.
CP: has received consulting and lecture fees from Actelion, Almirall, Biogen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva; has received research funding from Merck Serono, Novartis, Sanofi-Aventis, Teva.
Abstract: P1229
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: TYGRIS was a 5-year observational cohort study designed to obtain long-term safety data in natalizumab-treated MS patients in clinical practice.
Objectives: To examine the incidence and pattern of serious adverse events (SAEs) in a large postmarketing sample of natalizumab-treated MS patients.
Methods: Investigators monitored natalizumab-treated patients and reported SAEs occurring during the study. Malignancy incidence rates were compared with rates in the Surveillance, Epidemiology and End Results and Globocan databases.
Results: Of 6508 enrolled patients (US, 2207; rest of world, 4301), 4938 (76%) completed the 5-year study. At enrollment, mean (SD) age was 40.1 (10.44) years, and 91% of patients had prior immunomodulatory/immunosuppressant use. Patients received a median (range) of 44 (0-77) natalizumab doses before/during the study, accruing ≈21,795 patient-years of natalizumab exposure. Of 6434 dosed patients, 987 (15%) experienced ≥1 treatment-emergent (TE) SAE, 222 (3%) reported ≥1 TE SAE leading to natalizumab discontinuation, and no individual SAE occurred in ≥1% of patients. SAEs occurring in >0.5% of patients included urinary tract infection (0.8%), pneumonia (0.7%), progressive multifocal leukoencephalopathy (PML; 0.7%), and immune reconstitution inflammatory syndrome (0.6%). Fifty-five patients (< 1%) experienced ≥1 TE serious opportunistic infection, 44 of which were PML. Most PML cases (42/44) occurred after >24 infusions; 23 cases were anti-JCV antibody positive ≥6 months pre-diagnosis; serostatus ≥6 months prior to PML development was unknown or not reported in 21 cases. Two patients with PML had fatal outcomes. The malignancy incidence rate (449.0 per 100,000 patient-years [95% CI: 375.1-533.1]) was similar to rates in the general population (460.2 and 519.2 per 100,000 person-years); no trends between dosing and malignancy incidence were observed. Six subjects experienced hepatotoxic events, including cytolytic hepatitis (n=2), liver injury (n=2), toxic hepatitis (n=1), and hepatocellular injury (n=1); most cases had clear evidence of alternative cause or ≥1 confounder. Of 96 fatal events in 77 patients, most (91/96) were considered unlikely/not related to study drug or causality was not reported.
Conclusion: The nature, character, and rate of SAEs reported in this study of long-term safety data from natalizumab-treated patients in real-word settings are consistent with the drug"s known safety profile.
Disclosure: Supported by Biogen.
JF: received personal compensation for consulting, speaking, and scientific advisory boards from Biogen, Genzyme, Teva; received financial support for research activities from Biogen, Genentech-Roche, Genzyme, Teva.
CCI, MW, KE, BH, DS, PRH, LL, GB: employees of and may hold stock and/or stock options in Biogen.
NL, JS: contractors for Biogen.
PV: has received honoraria and consulting fees from Almirall, Bayer, Biogen, GSK, Merck-Serono, Novartis, Sanofi-Genzyme, Teva; has received research support from Bayer, Biogen, Merck-Serono, Sanofi-Genzyme.
MH: served on a medical advisory board for Biogen; serves on the editorial board of the Multiple Sclerosis Journal, has received speaker"s honoraria from Bayer-Schering, Biogen, Novartis; receives research support from Dystonia Ireland, the European Dystonia Foundation, the Health Research Board of Ireland.
CP: has received consulting and lecture fees from Actelion, Almirall, Biogen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva; has received research funding from Merck Serono, Novartis, Sanofi-Aventis, Teva.