Long‐term evolution of multiple sclerosis disability in the treatment era

Bruce Cree(University of California, San Francisco), Pierre‐Antoine Gourraud(University of California, San Francisco), Jorge R. Oksenberg(University of California, San Francisco), Carolyn Bevan(University of California, San Francisco), Elizabeth Crabtree‐Hartman(University of California, San Francisco), Jeffrey M. Gelfand(University of California, San Francisco), Douglas S. Goodin(University of California, San Francisco), Jennifer Graves(University of California, San Francisco), Ari Green(University of California, San Francisco), Ellen M. Mowry(University of California, San Francisco), Darin T. Okuda(The University of Texas Southwestern Medical Center), Daniel Pelletier(University of Southern California), H.‐Christian von Büdingen(University of California, San Francisco), Scott S. Zamvil(University of California, San Francisco), Alisha Agrawal(University of California, San Francisco), Stacy J. Caillier(University of California, San Francisco), Caroline Ciocca(University of California, San Francisco), Refujia Gomez(University of California, San Francisco), Rachel Kanner(University of California, San Francisco), Robin Lincoln(University of California, San Francisco), Antoine Lizée(University of California, San Francisco), Pamela Qualley(University of California, San Francisco), Adam Santaniello(University of California, San Francisco), Leena Suleiman(University of California, San Francisco), Monica Bucci(University of California, San Francisco), Valentina Panara(University of California, San Francisco), Nico Papinutto(University of California, San Francisco), W. Stern(University of California, San Francisco), Alyssa H. Zhu(University of California, San Francisco), Gary Cutter(University of Alabama at Birmingham), Sergio E. Baranzini(University of California, San Francisco), Roland G. Henry(University of California, San Francisco), Stephen L. Hauser(University of California, San Francisco)
Annals of Neurology
July 27, 2016
10.1002/ana.24747
Cited by 435Open Access
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Abstract

OBJECTIVE: To characterize the accrual of long-term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data used in clinical trials have long-term prognostic value. METHODS: This is a prospective study of 517 actively managed MS patients enrolled at a single center. RESULTS: More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long-term outcomes that were no different from those of the cohort as a whole. 25-OH vitamin D serum levels were inversely associated with short-term MS disease activity; however, these levels had no association with long-term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval [CI] = 7.2-14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5-22.5%) evolved from relapsing MS to secondary progressive MS (SPMS). INTERPRETATION: Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2-year endpoint was not a predictor of long-term stability. Finally, the data call into question the utility of annual MRI assessments as a treat-to-target approach for MS care. Ann Neurol 2016;80:499-510.

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