Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results

Abstract

BackgroundClinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.ObjectiveTo evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsThe Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.ResultsIn this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11–44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.ConclusionsInterim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.Trial registration numberNCT00493298.

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

“…In interpreting our findings, several factors, particularly epidemiology of melanoma, natalizumab‐associated progressive multifocal leukoencephalopathy (PML), various aspects of the TOUCH Risk Management (RiskMAP) Action Plan, and the Safety Surveillance Program in this RiskMAP (Table 3), potential pathophysiology, and an overview of pharmacovigilance efforts for opportunistic complications of medications, should be considered 6, 7, 8, 9, 10, 11, 13, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47.…”

“…A longer therapy duration would be expected if natalizumab caused melanoma via an immunologic pathway, unless existing nevi were already premalignant lesions. PML occurs after a long duration of rituximab and a short duration of brentuximab vedotin and ibrutinib (drugs used for hematologic malignancies), and after a variable time period following natalizumab 7, 8, 10, 13, 40, 41, 42, 43, 44, 46.…”

“…It examines incidence and pattern of serious infections, malignancies and other serious adverse events among natalizumab‐treated patients with multiple sclerosis in Canada and the United States. In an interim analysis based on follow‐up for 4821 natalizumab‐treated patients enrolled in a Tysabri Observational Protocol (TOP), an ongoing observational study conducted in Europe, Australia, Canada, and Argentina, 77% were followed up for at least 1 year and 52% for at least 2 years 46. The median follow‐up period was 26 months (range: 1–69).…”

“…The median follow‐up period was 26 months (range: 1–69). Eighteen patients were diagnosed with PML and one patient was diagnosed with melanoma 46. The distinction here is that while the Tysabri Safety Surveillance Program focuses on JCV‐associated PML and other opportunistic infections, TYGRIS, TOP, and other international registries focus on malignancies and opportunistic infections.…”

Use of Natalizumab in Patients with Multiple Sclerosis: 2015 Update

“…6 In the 5-year interim analysis of 4821 patients (mean follow-up 26 months), 91% of whom received ≥1 disease-modifying therapy (DMT) before initiating natalizumab therapy, mean ARR decreased from 1.99 in the 12 months before baseline to 0.31 on natalizumab therapy (84% reduction with p < 0.0001), and remained low. Additionally, mean EDSS scores remained unchanged up to 5 years in the analysis.…”