Clinical course after change of immunomodulating therapy in relapsing–remitting multiple sclerosis

Abstract

We examined the clinical course after switching disease-modifying therapy (DMT) in patients with relapsing-remitting multiple sclerosis (RRMS). Eighty-five consecutive RRMS patients who received weekly interferon beta-1a (IFN beta-1a) 6 MU i.m. for at least 18 months were enrolled. Baseline annualized relapse rate (ARR) for the 2 years prior to initiating therapy with IFN beta-1a was obtained from charts. All 85 patients received treatment with IFN beta-1a at 6 MU i.m. weekly for 18-24 months (mean 19.7 months). Treatment with IFN beta-1a reduced the mean ARR from 1.41 to 1.23 (P=0.005). All 85 patients were then switched to glatiramer acetate (GA) 20 mg s.c. daily and prospectively followed up for 36-42 months (mean 37.5 months). Patients were switched because of persistent clinical disease activity (n=62) or persistently unacceptable toxicity (n=23) as determined by the treating neurologist. Treatment with GA reduced the mean ARR from 1.23 to 0.53 (P=0.0001). Subgroup analysis showed that in patients who were switched because of lack of efficacy (n=62), the mean ARR was reduced from 1.32 on IFN beta-1a to 0.52 on GA (P=0.0001). In contrast, in patients who switched because of persistent toxicity (n=23), the mean ARR was reduced from 0.61 on IFN beta-1a to 0.47 on GA (P, non-significant). Our observations suggest that clinical observations such as relapse rate and tolerability may be used as criteria for switching DMT in clinical practice. More definitive consensus criteria incorporating magnetic resonance imaging and clinical observations for defining optimal response and tolerability need to be developed for the routine clinical management of RRMS patients receiving DMT.

The heritage of glatiramer acetate and its use in multiple sclerosis

“…For patients not responding to first line therapies GA can be offered as an alternative to so-called second line medications if there are concerns of tolerability/adverse events with the latter therapies. Most studies describe switches from IFNβ-1a or -1b to GA, reporting reductions in mean ARR after switching [81][82][83]. However, in those situations when the shift is due to failure of the previous treatment, results should be interpreted with caution because the regression to the mean phenomenon is a major concern.…”

“…Switching to glatiramer acetate Several trials have evaluated switching to GA from other MS therapies for safety and efficacy reasons [81][82][83]. For patients not responding to first line therapies GA can be offered as an alternative to so-called second line medications if there are concerns of tolerability/adverse events with the latter therapies.…”

Long-Term Adherence to Interferon β Therapy in Relapsing-Remitting Multiple Sclerosis

“…Recently, glatiramer acetate therapy was reported to represent a suitable option in patients who switched from IFNB therapy due to both PLE and SE [14,15,16]. …”

Review of the Clinical Debate Regarding Interventions for Multiple Sclerosis

“…77 Another study conducted by Caon et al evaluated 85 patients with MS who had switched to GA after discontinuing therapy with low-dose IFNβ-1a due to either suboptimal efficacy or persistent toxicity. 78 At the beginning of this study, the mean annualized relapse rate was 1.41. After a mean of 19.7 months of IFNβ-1a treatment, the annualized relapse rate had been reduced by 13% from baseline to 1.23 (P = 0.005).…”

“…After a mean of 37.5 months of treatment with GA injection (range of 36 months to 42 months), the mean annualized relapse rate had been significantly reduced by 57% to 0.53 (P < 0.001). 78 A more recent prospective, longitudinal study from Argentina included 114 patients with RRMS who failed first-line monotherapy and switched treatments after 3 years. 79 The primary outcome measure was the annualized relapse rate, and secondary outcome measures were the proportion of relapse-free patients and the median change in EDSS scores.…”