Volume 212 - Issue 4
Expanding the availability of medications for amyotrophic lateral sclerosis in Australia
Authors: Colin J Mahoney and Matthew C Kiernan
Med J Aust 2020; 212 (4): 189-189.e1. || doi: 10.5694/mja2.50482
Published online: 2 March 2020
Published online: 2 March 2020
To the Editor: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative condition with no cure. Only two treatments with class I evidence exist — riluzole1 and edaravone2 — both with unclear mechanisms of action and modest survival benefits. In Australia, riluzole remains the only treatment approved by the Therapeutic Goods Administration. The Pharmaceutical Benefits Scheme limits initiation of riluzole to patients with at least 60% of predicted forced vital capacity, although facial weakness may make this an unreliable target. Initial and continuing treatment requires patients to be ambulant; or to have good upper limb function or to be able to swallow; and not to have respiratory failure.
A recent retrospective study classified patients into different disease severity stages, ranging from 1 (one region involved) to 5 (death); patients with respiratory and nutritional failure were assigned to stage 4.3 The study identified that patients in stage 4 receiving 100 mg of riluzole daily did not progress to the next clinical stage (ie, death) as rapidly as those in milder stages. This suggests that the modest survival benefit experienced by patients taking riluzole comes about by extending the time spent at this stage. A quarter of patients present with bulbar or respiratory onset,4 making many ineligible for treatment, despite data suggesting they may benefit most.5 Mean survival in these forms of ALS is particularly short, meaning the modest survival benefit offered should be considered, as a majority of patients with advanced ALS do not wish to hasten death.6 A recent study of over 4000 trial participants confirmed benefit in both early and late stages,7 supporting use of riluzole throughout the disease. Few prospective studies on late‐stage treatments exist; patient choice in continuing treatment during advanced stages therefore remains paramount.
Prospective studies are needed to establish whether the benefit of riluzole is weighted towards more advanced disease. However, recent studies, along with the recognition of the clinical spectrum of ALS, indicate that the current Pharmaceutical Benefits Scheme criteria are too stringent. As we move towards precision‐based medicine, different profiles of therapeutic response are likely. Regulators will be required to rapidly respond to emerging data to ensure the right patients can access the right medications.
Competing interests
Matthew Kiernan is editor‐in‐chief of the Journal of Neurology, Neurosurgery and Psychiatry.
References
- Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994; 330: 585–591.
- Abe K, Aoki M, Tsuji S, et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double‐blind, placebo‐controlled trial. Lancet Neurol 2017; 16: 505–512.
- Fang T, Al Khleifat A, Meurgey J‐H, et al. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose‐ranging study. Lancet Neurol 2018; 17: 416–422.
- Talman P, Duong T, Vucic S, et al. Identification and outcomes of clinical phenotypes in amyotrophic lateral sclerosis/motor neuron disease: Australian National Motor Neuron Disease observational cohort. BMJ Open 2016; 6: e012054.
- Zoccolella S, Beghi E, Palagano G, et al. Riluzole and amyotrophic lateral sclerosis survival: a population‐based study in southern Italy: riluzole and ALS survival in Puglia. Eur J Neurol 2007; 14: 262–268.
- Albert SM, Rabkin JG, Del Bene ML, et al. Wish to die in end‐stage ALS. Neurology 2005; 12: 68–74.
- de Jongh AD, van Eijk RPA, van den Berg LH. Evidence for a multimodal effect of riluzole in patients with ALS? J Neurol Neurosurg Psychiatry 2019; 90: 1183–1184.