• 30
    Mar
  • Multiple Sclerosis Symposium and American Society of Hypertension

HypertensionMULTIPLE SCLEROSIS SYMPOSIUM

Long-term efficacy data for glatiramer acetate (Copaxone, Teva Pharmaceuticals), which is indicated for patients with multiple sclerosis (MS), constituted a centerpiece among two days of presentations at the Fifth Teva and Sanofi-Aventis International Symposium on MS. Several hundred interested professionals attended the meeting, which took place from May 12-14, in Tenerife, Spain.

Reduced Disability with Glatiramer: Results of a Long-Term Study

Prevailing opinion suggests that the most effective options currently available for treating MS include the immunomodulatory therapy glatiramer acetate (GA) and the beta interferons, all of which were approved based on successful two-year pivotal trials.
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Corey C. Ford, MD, PhD, Associate Professor of Neurology at the University of New Mexico in Albuquerque, said that although MS is a lifelong disease, the pivotal trials tell patients and physicians little about long-term control of symptoms and the likelihood of disease progression. Most studies of beta interferons are based on retrospectively gathered data with large gaps in monitoring, but only GA has been examined in a systematic, prospectively designed, long-term study of its use for more than a decade.

The ongoing U.S. Glatiramer Acetate (U.S. GA) Trial is now in its 15th year. Among the unique aspects of this trial are its in-clinic evaluations of patients to assess disability every six months and the fact that patients have been receiving GA monotherapy. No prospective studies of continuous interferon use go beyond four years, Dr. Ford said. Furthermore, patients who had withdrawn from the U.S. GA study (because they discontinued GA therapy for any reason) were sought for long­term follow-up clinical neurological assessment, as measured by the Expanded Disability Status Scale (EDSS).

As of this writing, 108 patients are receiving GA, out of an initial cohort of 232 patients who received at least one GA dose. Of the 124 patients who have withdrawn from the study, 50 have been followed over the long term.

The objective of the U.S. GA Study was to determine the efficacy and safety of GA treatment for up to 12 years among patients who had received at least one GA dose during the 30-month double-blind phase (the pivotal trial) or during the ongoing open-label extension study. Another purpose was to gather data about patients who had withdrawn from the study.

The first analysis covered the annual rate of relapse. The mean annual relapse rate, before GA therapy was initiated, was about 1.2%. For patients who continued to take GA, the relapse rate declined within a few years, to about 0.25% per year. The relapse rates during years 9 to 12 were even somewhat lower.

An analysis of the proportion of patients reaching EDSS thresholds of 4 (moderate disability), 6 (cane needed), or 8 (wheelchair needed) showed significantly reduced disability in the patients in the ongoing study compared with those who had withdrawn from the study (Table 1). The mean change was a loss of one-half step for patients continuing GA therapy and a loss of 2.24 steps, as assessed by the EDSS, for patients who had withdrawn, at a mean of about 4.3 years.

Table 1   Patients Receiving Ongoing Glatiramer Therapy versus Withdrawn Patients at 10 Years of Long-Term Follow-up

Withdrawn

Patients with

Ongoing

Long-Term

Cohort

Follow-up

EDSS Measure                         (n = 108)

(n = 50)

P Value

EDSS score of 4 (moderate disability)     24%

68%

<.000l

EDSS score of 6 (cane needed)               8%

50%

<.000l

EDSS score of 8 (wheelchair needed)       1%

10%

<.0l25

EDSS = Expanded Disability Status Scale.

The proportion of patients remaining clinically stable or improved (with an EDSS increase of 0.5 points or less) while continuing GA therapy was 58% in the modified intent-to-treat group (the original cohort minus patients who had originally been given placebo and who never received a GA dose), 62% in the ongoing therapy group, and 56% in the withdrawal group. That same “clinically stable or improved” EDSS measure at the 10-year follow-up visit revealed a rate of 62% for the ongoing therapy patients and 28% for the patients who had withdrawn from the study.

“Roughly two thirds are staying stable or improved over the long term,” Dr. Ford said.

He emphasized that the long-term GA EDSS scores compared favorably with those from natural history reports. For example, the 15-year report by Weinshenker showed 50% of patients reaching an EDSS threshold of 6, and the Pittock 10-year report showed that 28% of patients did. The rates in the U.S. GA Study were 8% for ongoing patients and 50% for those who withdrew. pharmacy uk

Dr. Ford noted that with a disease duration of about 15 years, nearly all patients receiving GA (89%) remained ambulatory and that 47% of patients who had ever received GA remained in the study and continued daily therapy.

He concluded that glatiramer provided reduced relapse rates and slowed the progression of disability over 10 years of continuous use in relapsing-remitting MS. However, he cautioned that we cannot be sure that the 50 patients who withdrew and who were followed are representative of the total cohort; similarly, we cannot be sure that the ongoing patients are completely representative of the natural history of MS.

“We can argue about that,” he said.

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