A method for evaluating treatment switching criteria in multiple sclerosis.
OBJECTIVE
We investigated a method to evaluate a treatment switching approach, namely treatment change after one multiple sclerosis (MS) relapse.


METHODS
Patients who experienced a relapse while on a first-line disease-modifying therapy, glatiramer acetate, were identified. Based on their subsequent course, patients were divided into two groups: those who changed treatment and those who did not. Patients were allowed to change to any other treatment. Subsequent annualized relapse rate and time to next relapse were compared in the two groups. Since patients were not randomized to treatment group, negative binomial and Cox regression models were used to control for several potential clinical confounders, including relapse severity, relapse duration, age, disease duration and presence of previous/combination therapy. In addition, an inverse probability of treatment weighting model was used to control for confounding. Several secondary analyses investigated patient subgroups.


RESULTS
Statistical modeling showed that there was no significant difference between groups in terms of relapse rate (rate ratio; 95% CI = 0.68; 0.35, 1.31) and time to next relapse (hazard ratio; 95% CI = 0.61; 0.30, 1.25). All secondary analyses confirmed these results. In addition, no significant difference in time to sustained progression on the Expanded Disability Status Scale was observed (p > 0.05). Our approach allowed investigation of the choice to change treatment after a relapse.


CONCLUSIONS
Our results showed that a single relapse may not be sufficient to indicate treatment failure. Although clinical confounders were addressed in our modeling, unmeasured confounders, particularly the presence of magnetic resonance imaging activity, may have biased our conclusion.
Healy
Brian C
BC
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA. bchealy@partners.org
Glanz
Bonnie I
BI
Stankiewicz
James
J
Buckle
Guy
G
Weiner
Howard
H
Chitnis
Tanuja
T
D000328:Adult; D057915:Drug Substitution; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015233:Models, Statistical; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate