DX56 Predictors of Switching First-Line Disease-Modifying Therapy for MS Patients

Thursday, May 30, 2013
Barbara E. Teter, PhD, MPH , State University of New York at Buffalo, Elma, NY
Neetu Agashivala, MS , Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ
Katelyn S. Kavak, MS , Department of Neurology, The Jacobs Neurological Institute, University at Buffalo, Buffalo, NY
Lynn Chouhfeh, MD , Department of Neurology, The Jacobs Neurological Institute, University at Buffalo, Amherst, NY
Ron Hashmonay, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Bianca Weinstock-Guttman, MD , State University of New York at Buffalo, Buffalo, NY
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Background: Patients with multiple sclerosis (MS) failing first-line disease-modifying therapy (DMT) may be switched to another DMT. However, no definitive algorithm exists to guide this practice.

Objectives: The aim of this retrospective study was to identify predictors of switching in patients with lack of response or limited response to a first-line DMT.

Methods: Data were extracted from the New York State MS Consortium longitudinal registry, comprising 14 New York MS centers or neurology practices. Inclusion criteria: diagnosis of clinically defined relapsing-remitting MS, ≥3 years of follow-up, and initial therapy with interferon β or glatiramer acetate. Lack of or limited response to first-line DMT was defined as a clinically determined MS event immediately preceding a DMT switch: (1) relapse; (2) Expanded Disability Status Scale (EDSS) worsening (increase of ≥1.0 for EDSS ≤5.5 or 0.5 for EDSS ≥6.0); (3) magnetic resonance imaging (MRI) worsening recorded as MRI worsening, new T2 lesions, new gadolinium enhancing lesions, or new black holes; or (4) a combination of 1–3. Nonswitchers were defined as those who remained on initial first-line DMT after a MS event; switchers were defined as those who changed DMT after a first MS event but before a second MS event. Predictors of DMT switching were identified using regression modeling with switching as the outcome variable and adjusted for age and EDSS at DMT initiation, duration from enrollment to DMT initiation and to most recent follow-up and physician center.

Results: Patients with lack of or limited response (N=606) were mostly female (77.4%), with mean age of 32.6 y at MS symptom onset and mean EDSS of 2.3 at DMT initiation; 35.3% of these patients switched therapy. The most common MS events defining lack of or limited response were EDSS worsening (25.2%), relapse(s) (21.5%), and MRI worsening (16.2%). Relative to 1 relapse, odds of switching were increased by status of  ≥2 relapses (Odds ratio [OR] 2.8; P=0.035), MRI worsening (OR 6.5; P<0.001) and EDSS worsening (OR 2.3; P=0.006).

Conclusions: MRI activity and EDSS progression were the most significant predictors of  switching therapy decision in patients with limited response to first-line DMT. MRI activity was 6.5 times more likely to be linked to a switch therapy decision as compared to 1 relapse. Future studies should evaluate the benefit of switching DMT based on MRI worsening to prevent long-term disability progression.