Characterize the relationship of isometric strength change in sentinel muscles with riluzole treatment  to survival in ALS.

Riluzole has positive effects on survival/functional scales in ALS (Miller 2012).  Riluzole has effects on isometric strength (Bensimon 1994).  Neck flexion, biceps/brachioradialis flexion, hip flexion, knee flexion are identified as sentinel muscles in ALS (Nakamura 2013, Khalaf 2019, Santos 2016, Slavin 1998).

128 consecutive ALS patients initiating riluzole therapy were assessed for ALS-FRS-R, respiratory function, isometric muscle strength measured by Medical Research Council scale.  Subjects were examined before and at approximately 4 weeks following initiation of riluzole 50 mg twice daily, vitamin E 1200 units daily, vitamin B12 5000 micrograms daily, folic acid 2000 mcg daily, vitamin E vitamin D 5000 mcg daily.  Statistical analysis employed MedCalc Software version 19.0.5  ; 2019.

80/128 [ 62.5 % ] ALS patients showed improvement in one or more sentinel muscles following riluzole treatment and 48/128 [ 37.5 % ] ALS patients did not. Subjects in the ‘strength improved’ cohort demonstrated median survival = 21.0 months [ 95% CI =17.0 to 23.0 months ] that was significantly prolonged [ P=0.001 Kaplan-Meier Logrank test ] compared with the subjects in the ‘strength not improved’ cohort median survival = 12.0 months [ 95% CI = 5.0 to 18.0 months ].

A proportion of ALS patients receiving riluzole/vitamin E/vitamin B12/folic acid/vitamin D show improvement in isometric muscle strength in sentinel muscles observed within 4 weeks of treatment initiation that is associated with slower disease progression as measured by increased survival.  Assessing early response to riluzole treatment may be an independent milestone that might be employed in prognostic models as well as prediction model based clinical trial analysis.  Replication of this observation as well as further investigation of early non-responders with respect to riluzole pharmacokinetics may provide insights as to whether patients are treatment resistant or may need riluzole dose adjustment.