Search

Supplemental material, sj-docx-1-mso-10.1177_20552173231167079 for Severity and worsening of fatigue among individuals with multiple sclerosis by Amber Salter, Alexander Keenan, Hoa H Le, Kavita Gandhi, Maria Ait-Tihyaty, Samantha Lancia, Gary R Cutter, Robert J Fox and Ruth Ann Marrie in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Aim: To compare the characteristics and outcomes of patients who initiate disease modifying treatments (DMTs) early compared to later over a 5-year period. Methods: Data came from NeuroTransData (NTD) MS registry run by a network of Germany-wide neurologists. Study included patients initiating DMTs between Jan 1, 2009, and Oct 1, 2021. Patient cohorts were defined based on the time of initiation of their first DMT relative to the date of RRMS diagnosis: Cohort 1 ( 12 months to 24 months to < 5 years, n=788), and Cohort 4 treatment (more than 5 years, n=1604). Results: There were no meaningful differences in age, time since symptoms manifestation, or EDSS across the cohorts at time of first DMT initiation (index). Relapse activity appeared to be a leading reason for DMT initiation with at least one relapse experienced 1-year pre-index by 43.6% patients in cohort 1 compared to 31.3%, 27.2% and 18.1% of patients in cohorts 2,3,4, respectively. Glatiramer acetate/interferons were most used in cohort 1 (74.4%) and least in cohort 4 (54.5%). The use of other DMTs, including monoclonal antibodies, increased with delayed time to DMT initiation. For cohorts 1 and 2, average (SD) annual relapse rate (ARR) was 0.4 (0.6) and 0.3 (0.6) at year 1 but declined to 0.08 (0.3) and 0.1 (0.3) by year 5, respectively. In vontrast, average ARR mean (SD) was in a narrow range for cohorts 3 [0.1 (0.4)- 0.2 (0.5)] and 4 [0.05 (0.2)-0.1 (0.3)] through the study period. EDSS for patients delaying DMTs numerically worsened than those who initiated early over 5 years [e.g., mean (SD) worsening from 1.3 (1.1) at year 1 to 1.9 (1.6) at year 5 in cohort 3 compared to stable EDSS of 1.5 over 5 years in cohort 1]. EDSS results must be interpreted with caution due to high level of missingness. Conclusions: Neurologists appear to make a reasonable prognosis regarding potential changes in patients’ EDSS status over a 5-year period and whether to initiate treatment or wait and see clinical changes. A potential trade-off with the wait and see approach is that more efficacious treatments are used as initial therapy. Nevertheless, the benefit: risk of such treatments may be an important consideration along with other disease-related factors in individualizing patient treatment decisions.

Aim: To identify, characterize, and compare outcomes of patients with high persistency (HP) and low persistency (LP). Methods: Study data came from MS disease registry of the doctors-run German NeuroTransData(NTD) network of neurologists and psychiatrists capturing demographic, clinical history, and clinical variables during outpatient visits. Inclusion criteria were patients with RRMS, treatment naïve or 1 switch, and with one future visit after therapy start. Only patients with an index date (i.e., therapy start) after 1 January 2009 were retained.From patient distribution, HP was defined as continuous exposure time of at least two years, while LP was less than two years. Propensity Score Matching was performed on age, sex, relapses, baseline EDSS, and time since MS manifestation for 1 year pre-index. Cox regression was used to compare time to first relapse and time to 12-week confirmed disability progression (CDP). Results: In total, 2,367 patients were matched for HP and LP cohorts. The mean [standard deviation (SD), interquartile range (IQR)] for age was 38.3 (10.7; 29.9-46.4) years, 0.7 relapses in the past year (0.8; 0-1), mean baseline EDSS was 2.0 (1.5;1-3), and symptoms manifestation time was 6.6 years (sd:7.2; 0.96-10.3); 76.2% were females. Mean (SD; IQR) DMT exposure time in years was 0.78 years (0.57;0.29-1.2) for the LP cohort and 4.7 (2.2;2.9-6.2) for the HP cohort.The use of DMTs was: 49.1% on injectables, 40.5% on orals, 2.2% on infusions (excluding monoclonal antibodies) and 8.2% on monoclonal antibodies. Using Cox Regression, the hazard ratio (95% CI) on time to relapse for LP versus HP cohort was 1.4 (1.3-1.5) (Wald p value: < 0.001). For time to first CDP, it was 1.2 (1.0-1.3) (Wald p value: 0.011). Conclusion: HP had better outcomes on time to first relapse than matched LP cohort. The minor difference in CDP risk between two cohorts may be due to 2 years limited follow-up. These findings support the importance of identifying appropriate DMTs for individual patients with due consideration to their underlying disease characteristics in maintaining treatment persistency and improved outcomes.