Objective:

To retrospectively examine the tolerability and benefit of FDA-approved combined pharmacological treatment in patients with amyotrophic lateral sclerosis (ALS).

Background:

Oral edaravone, TURSO/sodium phenylbutyrate, riluzole and high-dose methylcobalamin have been independently shown to slow disease progression in patients with ALS.  These drugs differ in their mechanisms of action, therefore, combined drug therapy may offer the most benefit to improve clinical outcomes.

Design/Methods:

Retrospective data collection from 110 medical records of patients with ALS that attended regular ALS clinic visits over a 15-month period were aggregated. Of those, records from 31 patients with greater than 3-months of ALSFRS-R and slow vital capacity progression rates, and stable treatment status (on all four treatments vs. partial treatment) were analyzed. Partial treatment was defined as lack of consistent treatment due to tolerability, insurance coverage or compliance. Descriptives and t-tests were conducted to determine if differences in progression rates differed between treatment groups (p<0.05).

Results:

Patients in the full treatment group (n=15) were 73% male, 67% spinal onset and 63.9 years old (+/-10.6).  The partial treatment group (n=16) was 50% male, 75% spinal onset and 57.4 years old (+/-11.0).  Those on a full treatment demonstrated slower ALSFRS-R progression rates per month (95% CI, -0.77- -0.12) vs. those on partial treatment (95% CI, -1.5- -0.89)(-0.44 vs. -1.2, p=0.002); and slower SVC progression (-0.86, 95% CI 0.29- -2.00) vs. those on partial treatment (-2.90, 95% CI -1.76- -4.04)(p=0.02).

Conclusions:

This small ALS case series demonstrates that although combination therapy is feasible, there are significant limitations in drug obtainment. This retrospective pilot study provides preliminary evidence that the most benefit is derived from implementing combination treatment and warrants further investigation.