Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: A 16-year non-concurrent cohort study

Abstract

Background: Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS).

Methods and findings: We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer.

Conclusions: This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

Fig 1. Flow diagram of the study population.

Fig 2

Kaplan–Meier estimates for the time to treatment failure of all (A), exclusive and non-exclusive SUS patients (B), gender (C), comorbidities after starting treatment (D) and initial DMT treatment (E). Abbreviations: DMT, disease-modifying therapy; CI, confidence interval; IM-IFNβ-1a, intramuscular interferon beta-1a; SC-IFNβ-1b, subcutaneous interferon beta-1b; SC-IFNβ-1a, subcutaneous interferon beta-1a.

Fig 3

Kaplan–Meier matched comparisons for the time to treatment failure of IM βINF- 1a vs. SC βINF-1b (A), IM βINF- 1a vs. glatiramer (B), IM βINF- 1a vs. SC βINF-1a (C), SC βINF- 1b vs. glatiramer (D) SC βINF- 1b vs. SC βINF-1a (E) and Glatiramer vs. SC βINF-1a (F). Bonferroni adjustment for multiple comparisons. The significance level is p ≤ 0.008 (6 comparisons). Abbreviations: IM-IFNβ-1a, intramuscular interferon beta-1a; SC-IFNβ-1b, subcutaneous interferon beta-1b; SC-IFNβ-1a, subcutaneous interferon beta-1a.