Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan

Abstract

IntroductionNatalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis.MethodsDuring the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs).ResultsThe safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing–remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period.ConclusionThe safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation.FundingBiogen Japan Ltd (Tokyo, Japan).

High prevalence and indexes of anti-John Cunningham virus antibodies in a cohort of Chinese patients with multiple sclerosis

“…We identified a prevalence of anti-JCV-Abs in 80% Chinese MS patients, which is the highest reported rate in the world (47–68%, Figure 2 ). 9 , 10 The majority of seropositive MS patients also have a high anti-JCV index (≥1.5), and the sero-status appear to remain unchanged for most subjects in subsequent years. These findings may impact the recommendation of DMT for Chinese MS patients.…”

“… Seroprevalence of anti-John Cunningham virus antibody (JCV-Ab) in multiple sclerosis (MS) patients across different regions in the world. 8 , 9 Prior exposure to natalizumab was highly variable (0–98%). …”

“…Invariably, patients with high anti-JCV index may not want to be exposed to the risk of PML. 9 In other words, patients who have developed highly active disease might consider DMTs with a lower risk of PML, when balancing efficacy and other serious side effects. Further longitudinal studies are required to identify the cause of high prevalence in Chinese people, as a lower seroprevalence (36%) and proportion with high anti-JCV index (≥1.5, 48%) was noted in Perth (personal communication, Communication with Allan Kermode, 17 March 2018), a city of similar latitude and longitude as Hong Kong but in the Southern hemisphere with predominant Anglo-Celtic ethnicity.…”

Real-world evidence and product development: Opportunities, challenges and risk mitigation

“…Pragmatic studies can also help determine safety and efficacy in special groups in real-world settings. For example, natalizumab was registered for multiple sclerosis in Japan on the premise that a real-world study is conducted to assess its safety, efficacy and tolerability in clinical practice [18].…”

Long-term effects of natalizumab on MRI activity and clinical outcomes in Japanese patients with relapsing-remitting multiple sclerosis

“…Although its safety and efficacy, including MRI outcomes, have been demonstrated in Japanese RRMS patients in a phase II clinical trial, the study duration was only 24 weeks. Some longer term evidence is available from an open-label extension of the phase II trial [ 12 , 13 ] and an interim analysis of a post-marketing surveillance (PMS) study [ 14 ]. Despite the effectiveness of natalizumab being best characterized by MRI, neither of these longer-term studies assessed MRI outcomes, which is a common problem of real-world studies due to limited insurance coverage in many other countries.…”