JMIR Publications

ABSTRACT

Background:

Spinal muscular atrophy (SMA) is an autosomal recessive genetic neuromuscular disorder with progressive muscle weakness and atrophy, mainly caused by lower motor neuron degeneration resulting from decreased levels of the survival motor neuron protein. Recently, three disease-modifying therapies for SMA (nusinersen, onasemnogene abeparvovec, and risdiplam) were approved in Japan that are expected to improve the prognosis of patients with SMA. Long-term clinical follow-up of adult patients treated with disease-modifying therapies and the natural history of SMA are essential to assess the real-world effectiveness of available treatments. Until recently, nusinersen was the only treatment option for patients with SMA in Japan; however, because Japanese approval of nusinersen was based on global clinical trials in infants and children aged 0-15 years with SMA, the effectiveness of nusinersen in adult patients has not been fully assessed in Japan. In addition, longitudinal clinical data of adult patients have not been systematically collected in Japan.

Objective:

This longitudinal observational study of adult patients with SMA who have been diagnosed with 5q-SMA in Japan aims to gain a better understanding of the natural history of SMA, as well as the long-term effectiveness of disease-modifying therapies. Here, we describe the protocol for the study.

Methods:

The Japan REgistry for Adult subjeCTs of Spinal Muscular Atrophy (jREACT-SMA) study is a longitudinal (prospective and retrospective) observational study with a 60-month prospective follow-up being conducted at 19 investigational sites using the newly established jREACT-SMA registry. Patients ≥18 years of age with genetically confirmed 5q-SMA have been or will be enrolled in the registry from December 2020 to May 2022. The planned enrollment is 100 patients. The protocol was approved on September 28, 2020 (approval number: 2020-0289) by the ethical review committee of Nagoya University. Registration, demographics, genetic diagnosis, motor functions, patient-reported outcomes/quality-of-life outcomes, and other clinical data have been or will be collected.

Results:

Patient registration and data collection are ongoing.

Conclusions:

This jREACT-SMA study will provide longitudinal prospective follow-up data in adult patients with SMA in Japan, including data on the natural history of the disease and data on the long-term effectiveness of disease-modifying therapies. Clinical Trial: University Hospital Medical Information Network [UMIN] Center Clinical Trials Registry: UMIN000042015