Early Treatment with Natalizumab Is Associated with Improved Long-Term Cognitive and Physical Performance in Multiple Sclerosis: Results from MS PATHS (4970)

Objective: To report the association of early versus delayed natalizumab treatment with clinical outcomes in the real world setting in patients with MS. Background: The impact of early versus delayed high efficacy DMT is uncertain. This important question can be addressed by a combination of RCTs (ongoing) and real-world evidence (this report). Design/Methods: 333 patients were included across 7 US sites. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the TOUCH registry. Clinical outcome was defined using Processing Speed Test (PST; SDMT), Manual Dexterity Test (MDT; 9HPT), Walking Speed Test (WST; 25FW) and Patient Derived Disease Steps (PDDS). Associations were tested using TTNT as a categorical variable (≤ 3 years versus > 3 years; and quintiles) and as a continuous variable, adjusting for age, disease duration, sex, race, years of education, smoking status, year of natalizumab initiation, and proportion of time on natalizumab. Linear mixed models were used to address within-subject and within-site clustering. Results: TTNT varied from 0 to 20 years; about 1/3 of patients were treated within 3 years. After adjusting for age and disease duration, patients with shorter TTNT had better scores on the PST (adjusted mean = 53.5 in quintile 1 vs. 36.8 in quintile 5, p Conclusions: In the real-world setting, shorter intervals between diagnosis and treatment with natalizumab were associated with less disability in later years. MRI correlates and additional sensitivity analyses will be presented. Strengths and limitations of the current analyses will be discussed. Disclosure: Dr. Ontaneda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting from Biogen Idec, Genentech, Genzyme, Merck, Novartis.. Dr. Ontaneda has received research support from Funding from PCORI, NIH, NMSS, Race to Erase, Genentech, Genzyme, Novartis.. Dr. Mowry has received personal compensation in an editorial capacity for UpToDate. Dr. Mowry has received research support from Biogen, Genzyme, Teva, and Sun Pharma.Dr. Newsome has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Celgene, EMD Serono, Genentech, medDay Pharmaceuticals, and Gerson Lehrman Group.. Dr. Newsome has received research support from Biogen, Genentech.Dr. Naismith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Alkermes, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, TG Therapeutics, Viela Bio. Dr. Naismith has received personal compensation in an editorial capacity for Associate Editor, NEJM Journal Watch. Dr. Nicholas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting, research, and/or speaking (Biogen, Celgene, EMD Serono, Genentech, MSAA, National MS Society, Novartis, PCORI, and Sanofi).. Dr. Nicholas has received research support from Consulting, research, and/or speaking (Biogen, Celgene, EMD Serono, Genentech, MSAA, National MS Society, Novartis, PCORI, and Sanofi).. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Williams was involved as an investigator. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Fisher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Fisher holds stock and/or stock options as a full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Fisher was involved as an investigator. Dr. DeMoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. DeMoor holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. DeMoor was involved as an investigator. Dr. Bohn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Bohn holds stock and/or stock options in Biogen. Dr. Ho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ho holds stock and/or stock options in Biogen.Dr. Sandrock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Sandrock holds stock and/or stock options in Holds stock/options in Biogen which sponsored research in which Dr. Sandrock was involved as an investigator. Dr. Sandrock holds stock and/or stock options in Holds stock/options in Biogen. Dr. Rudick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Rudick holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Rudick was involved as an investigator.