Clinical Data Associated With the Therapeutic Response to Glatiramer Acetate in Multiple Sclerosis Patients

Abstract

Background: The increasing appearance of new drugs is making more difficult the choice of
treatment in multiple sclerosis. According to different criteria, between 20 to 50% of the patients
with multiple sclerosis (MS) treated with the classical disease modify treatments (DMT) will
have an incomplete response and will need a change for more aggressive therapies. For this reason
it is of great importance to improve the selection process in these patients to avoid treatment
failures, side-effects and unnecessary risks. The utility of clinical and epidemiological data for
the prediction of the therapeutic response to the different MS treatments, and particularly to
glatiramer acetate (GA), is insufficient and contradictory.
Objective: To develop a predictive model of clinical data associated with the clinical response
to GA.
Methods: Observational retrospective study by reviewing medical charts from October/2002 to
February/2012. Data analysis was conducted from February/2014 to February/2015. Inclusion
criteria: Relapsing-remitting multiple sclerosis (RRMS McDonald 2010) with ≥1 relapses in
the previous 2 years, and ≥2 years of treatment with GA. All the patients included in this study
were treated with GA 20 mg injected subcutaneously once daily as the newer formulation of
GA 40 mg 3 times weekly was not approved at the time of the study. Definitions: Responders:
≤1 relapse and no disability progression; Non-responders: ≥2 relapses and/or disability
progression. Disability progression: EDSS increase ≥1.5 points if basal EDSS=0; increase ≥1
if basal EDSS=1-5; increase ≥0.5 if basal EDSS ≥5.5. Statistical analysis: logistic regression.
Association variable: odds ratio.
Results: Two hundred and four subjects included. Responders: 137 (67.5%). Number of
relapses in the 2 years before GA onset was associated with a worse clinical response (odds
ratio (OR): 1.4; IC 95%: 1.12-1.74%). Accuracy of this model (AUC: 63.5%; IC 95%: 56.2-
70.7%); Diagnostic parameters: Sensitivity: 40%; specificity: 79.8%, positive predictive value:
78.6; negative predictive value: 41.7.
Conclusions: GA was associated with a better response in Relapsing-remitting multiple
sclerosis (RRMS) patients with low-moderate disease activity. This model could be improved
incorporating serological, genetic and imaging data.