Non-self-sufficiency as a primary outcome measure in ALS trials

Abstract

Our objective was to assess non-self-sufficiency (NSS) in ALS as an outcome measure in therapeutic trials. Using data from the control arm of two randomized trials and an observational study, associations between NSS (score ≤2 in the ALSFRS-R items for swallowing, cutting food and handling utensils, or walking) and the total ALSFRS-R score, forced vital capacity (FVC), and survival at selected time-points until death or 48 weeks, were assessed. These measures were used as surrogates of relevant functional impairment. Of 82 self-sufficient (SS) patients at baseline, 32 (39.0%) became NSS at four weeks and increased to 72 (87.8%) at the end of follow-up. A significant association was found between NSS, ALSFRS-R score and FVC at 24, 36 and 48 weeks. Thirty-four subjects died (41.5%). Compared to SS patients (median survival, 27.9 months), individuals becoming NSS at four weeks were at increased risk to die (median survival, 23.6 months, p = 0.02). NSS status at four weeks predicted survival even after adjustment for ALSFRS-R total score, age, gender, site of onset, disease duration, BMI, and FVC. ‘Walking’ was the only predictor of survival when adjusting for all covariates. In conclusion, NSS status is a possible endpoint to investigate short-term efficacy of treatments of ALS.

Key words:

• Amyotrophic lateral sclerosis
• non-self-sufficiency
• outcome measures
• clinical trials

Acknowledgements

The study could be performed thanks to access to the data of two published trials:

Lithium trial (Neurology. 2010;75:619–25)

Acetyl-L-carnitine trial (Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:397–405).

Declaration of interest

E. Pupillo has received funding from the American ALS Association and Italian Ministry of Health for data management and data monitoring of an observational study protocol. She received funding from the Italian Drug Agency (AIFA) for data monitoring and study management of a randomized clinical trial. C. Lunetta has received compensation for board membership of Italfarmaco.

G. Logroscino has received grants from the European Union, grants from the Italian Ministry of Health, Ministry of School, University and Research, Apulia Region. A. Chiò reports grants from European Union, grants from Italian Ministry of Health, outside the submitted work; and has served on scientific advisory boards for Biogen Idec and Cytokinetics, Inc. and Italfarmaco.

E. Beghi has received money for board membership by Viropharma and EISAI; has received funding for travel and speaker honoraria from UCB-Pharma, GSK and for educational presentations for GSK; has received grants for research activities from the Italian Drug Agency, Italian Ministry of Health, Sanofi-Aventis and the American ALS Association.

B. Marin, E. Bianchi, L. Tremolizzo and P. M. Preux report no conflicts of interest.