To report the association of early versus delayed natalizumab treatment with clinical outcomes in the real world setting in patients with MS.

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).

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.

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 < 0.00001) and MDT (25.4 s vs. 34.1 s , p = 0.0001), and trended toward faster walking speed (7.1 sec vs. 8.9 sec) and lower PDDS scores (2.3 vs. 3.9) an average of 12.1 years after diagnosis. Results from all 3 analysis methods were consistent.

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.