Long-Term Persistence with Injectable Therapy in Relapsing-Remitting Multiple Sclerosis: An 18-Year Observational Cohort Study

Abstract

Disease modifying therapies (DMTs) reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS). Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA) or interferon-β 1a/1b (IFN-β) between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches) was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2%) were lost to follow-up and 160 (11%) moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54%) started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort

“…This is consistent with previous Canadian studies 14,25,29. We suggest that this may be due to the availability of DMTs.…”

“…However, it is important to note that 57% of these individuals eventually resumed their initial DMT or started a different DMT, with the majority occurring within 1 year of discontinuation. Our findings are similar to results from a recent study at the Calgary MS Clinic which reported 54% of individuals restarted a DMT after an initial discontinuation 29. These temporary disruptions in therapy may have been due to monitoring recommendations for withholding doses for typically transient issues like liver enzymes or hematologic abnormalities.…”

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France

“…Notably, the age at diagnosis and gender ratio are similar to those reported in recent epidemiological surveys of MS in France [16, 17]. Moreover, age and disease duration at start of treatment, gender ratio, EDSS score and pre-treatment exacerbation rates were generally similar to those reported in other cohorts of patients starting GA or interferon-β in Spain [6], Britain [18] and Canada [4]. The rather long disease duration when GA was initiated (8 years) may reflect the fact that the study was initiated shortly after GA was first made available in France, and there was a reservoir of patients who could not be treated by interferon-β awaiting a new treatment.…”

“…Nonetheless, between 2010 and 2014, after the introduction of oral DMTs, around one-third of patients in the national OFSEP patient registry for MS were not prescribed any DMT [15]. A high proportion of untreated patients who discontinue GA or interferon-β without another DMT being introduced has also been reported in a large Canadian cohort [4]. In general, clinical outcomes were worse in patients who discontinued GA than in those taking GA continuously, although it is not possible to determine the direction of any causality.…”

Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study

“…Continued treatment with IFN-β therapy is important to achieve maximum treatment efficacy, [8] but data from clinical trials and registries show that IFN-β therapies have a treatment discontinuation rate of between 14 and 44%, which may lead to disease reactivation [9]. The causes of IFN-β discontinuation may also change as a function of time.…”