Untreated patients with multiple sclerosis: A study of French expert centers

Abstract

Background and purpose Disease‐modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. Methods We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Results Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7–31.9) were not receiving any DMT. Although patients with a relapsing‐remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2–15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing‐remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44–0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74–0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. Conclusion A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

“…If, on one hand, this is quite expected on the basis of existing literature, 30 - 32 on the other hand, our finding conflicts with other authors who observed better outcomes in those patients who withdrew their DMTs after a prolonged period without relapses. 33 - 35 However, our data discourage permanent discontinuation or even temporary interruption of the initial DMT even in patients who early achieved the NEDA-3 status and remained stable over time.…”

Estimation of sample size in randomized controlled trials in multiple sclerosis studying annualized relapse rates: A systematic review

“…For the present article, we used 0.73 as this value was obtained from a large sample of French RRMS patients followed in tertiary care centres (86% treated; 14% untreated). 5 Among these patients, ARR variability is rather high and overdispersion is supposed to be smaller among very selected MS patients for a phase 3 study. Thus, using an overdispersion value set at 0.73 is probably conservative and usable for most phase 3 studies in RRMS.…”

“…For both, we performed one SSE based on the data provided in the statistical analysis plan (expected ARR) and another based on the observed ARR as a sensitivity analysis. For the NB method, overdispersion was set to 0.73, according to the value obtained on a sample of 11,693 French RRMS patients, 5 but was also tested for other overdispersion values between 0.5 and 1.…”

Performance of administrative databases for identifying individuals with multiple sclerosis

“…Also, since 2016, new drugs have been reimbursed and were not considered in this study. However, there are still cases of benign MS that do not require any treatment 12 . Therefore, our conclusions are unlikely to change.…”

“…Moreover, benign MS cases do not necessarily require the initiation of disease-modifying therapy or hospitalization. Indeed, the number of cases without treatment is estimated at 31% 12 . Furthermore, the accuracy of coding diagnoses in the hospital discharge records for MS is uncertain 13 , 14 .…”