Evaluating the Effect of Disease Duration in High Efficacy Versus Mid Efficacy Disease Modifying Therapies: Could This Help in Deciding When to De-escalate?
Brandi Vollmer1, Kavita Nair1, Stefan Sillau1, John Corboy1, Enrique Alvarez1
1University of Colorado
Objective:

Identify baseline characteristics associated with future disease activity in multiple sclerosis(MS) patients comparing oral and infusible disease modifying therapies(DMTs).

Background:
Infusible disease modifying therapies(DMTs)(rituximab, natalizumab) demonstrated higher effectiveness over oral DMTs(fingolimod, dimethyl fumarate). However, identifying patients likely to experience disease activity in clinical practice is still a challenge.
Design/Methods:

Relapsing-remitting MS(RRMS) patients prescribed fingolimod, dimethyl fumarate, natalizumab or rituximab at the Rocky Mountain MS Center at the University of Colorado were followed for 24 months or until drug discontinuation. Patients were evaluated for disease activity, defined as experiencing a clinical relapse, new T2 lesion and/or gadolinium enhancing lesion(GdE). Logistic regression was used to compare disease duration and DMT groups.

Results:
Of the 1004 RRMS patients, 509 and 495 received oral and infusible DMTs, respectively. Among those receiving oral DMTs, 36.4% experienced disease activity versus 21.2% among those receiving infusible DMTs. Disease duration was similar between patients on infusible(10.67 years) and oral(10.15 years) DMTs(p=0.215). Patients receiving oral DMTs with a disease duration ≤12 years had greater odds of experiencing disease activity overall(OR=2.19,p<0.001) and new T2 lesions(OR=1.91,p<0.011) compared to those >12 years. There was no significant difference between disease duration groups for GdE lesions or clinical relapses. In the infusible DMT group, there was no significant difference when comparing those with a disease duration ≤12 years to those >12 years for disease activity overall, or individual measures. The odds of experiencing disease activity with oral versus infusible DMTs is greater in patients with a disease duration ≤12 years(OR=2.69,p<0.001) than patients with a disease duration of >12 years(1.12,p=0.689). The disease duration at which there is no significant effect between oral and infusible DMTs decreases when examining by 5 year increments of age.  
Conclusions:
Higher efficacy therapies appear to have a disproportionately larger effect among those with a disease duration ≤12 years. Additional predictive modeling will be presented. 
10.1212/WNL.0000000000204280