Incidence and factors associated with treatment failure in the CLIMB multiple sclerosis cohort study


SA Gauthier, BI Glanz, M Mandel, Antonios Tsagkaropoulos, Mohit Neema, James Stankiewicz, Ashish Arora, Yang Duan, Zsuzsanna Liptak, Svetlana Egorova, Guy J Buckle, Rohit Bakshi, CRG Guttmann, SJ Khoury, and HL Weiner. 2009. “Incidence and factors associated with treatment failure in the CLIMB multiple sclerosis cohort study.” J Neurol Sci, 284, 1-2, Pp. 116-9.


OBJECTIVE: To determine the rate of treatment failure in patients outside of a controlled treatment trial and to ascertain the factors physicians used to make this decision. METHODS: One hundred and thirty four patients with the diagnosis of relapsing-remitting (RR) multiple sclerosis (MS) or clinically isolated symptom (CIS) enrolled in the CLIMB study (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital) were treated with either interferon beta or glatiramer acetate as their initial treatment for MS. RESULTS: The probability of failing initial treatment within 3 years was 30%. Clinical activity, defined as relapses and/or progression in disability, determined treatment failure in 35.7% (n=10) of nonresponders. New T2 hyperintense or gadolinium-enhancing lesions on MRI was used to define treatment failure in 28.6% (n=8) and new MRI lesions were used in combination with clinical activity in 35.7% (n=10). Treatment failures had a higher T2 hyperintense lesion volume (p=0.015) and number of gadolinium-enhancing lesions (p=0.0001) on the enrollment MRI than responders. CONCLUSIONS: These observations demonstrate that treating physicians use both clinical and MRI parameters to define a response to treatment and initiation of a treatment change and that baseline MRI identified those with increased risk of treatment failure.