Treatment continuity of amyotrophic lateral sclerosis with available riluzole formulations: state of the art and current challenges in a ‘real-world’ setting

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare multisystem neurodegenerative disease leading to death due to respiratory failure. Riluzole was the first disease modifying treatment approved in ALS. Randomized clinical trials showed a significant benefit of riluzole on survival in the months following randomization, with a good safety profile. ‘Real-world’ studies suggested that the survival benefit of riluzole is substantially greater, with an extended survival ranging between 6 and 19 months. The main limiting associated adverse effects of riluzole are non-severe gastrointestinal complications and an elevation of liver enzymes, observed in 10% of patients. While different classes of drugs have been approved in some countries, riluzole remains the gold standard of therapy. Dysphagia induced by ALS is a major challenge for food intake and riluzole administration. Tablet crushing is associated with a loss of drug intake and a risk of powder aspiration, which jeopardizes the benefits of riluzole. Riluzole oral suspension (ROS) and oral film (ROF) allow riluzole intake in patients with dysphagia. Both formulations are bioequivalent to riluzole tablets with a good safety profile albeit transient oral hypoaesthesia. In case of severe dysphagia, ROS can be used with percutaneous endoscopic gastrostomy. ROF, the last approved formulation, requires low swallowing capacities and may contribute to maintain the efficacy of riluzole when tablets are inadequate according to patient’s status and/or preferences. To optimize treatment continuity in newly diagnosed patients, the expected psychological impact of formulation switching that may be perceived as the sign of disease progression should be anticipated.

Keywords:

• Amyotrophic lateral sclerosis
• riluzole
• oral film
• dysphagia
• adherence
• treatment continuity

Acknowledgements

The authors wish to thank Hervé Bismut (Geminicis, Paris) for writing, editorial support, and formatting assistance that was funded by Zambon France.

Declaration of interest

P.Cor. serves on the editorial advisory board of Amyotrophic Lateral Sclerosis and of The Revue Neurologique, reports consultancies or advisory boards for Amylyx, Biogen, Cytokinetics, Ferrer, Mitsubishi Tanabe Pharma, VectorY and Zambon, serves on Drug Safety Monitoring Board for Quralis, and received a research grant from Biogen.

N.G, M.-H. S. and A.V. report consultancies or advisory boards for Effik and Zambon.

P.-F. P. received personal compensation for consulting and oral presentations from Biogen, Zambon, Effik, Clene Inc, Servier, Amylyx and Orphazyme. received research grants from the ANR, DGOS, ARSla, JPND and Effik, and received funding for congress attendance from Effik and Zambon.

P. Cou. reports consultancies or advisory boards for, Amylyx, Biogen, Cytokinetics, Mitsubishi, Effik and Zambon.

Additional information

Funding

No funding was received.