Efficacy Endpoints: Disease progression (persistent worsening of at least one point in Expanded Disability Status Scale), relapse-free rate, number of relapses at 12, 24, and 36 months, change in disability scores, and hospitalization rate.
Harm Endpoints: Death or systemic toxicity
Who Was In The Studies? Patients of any age and gender with definite MS, regardless of severity. Patients were typically female in the age range of 18 to 50 years.
Narrative: Multiple sclerosis is a chronic inflammatory disease that causes damage to myelin nerve fibers. Common clinical forms of the disease are ‘relapsing-remitting’ (RRMS) and ‘progressive’ MS. RRMS is characterized by periods of normal health interrupted by relapses of illness, while in progressive MS illness is persistent and worsening. Glatiramer acetate (GA) or Copaxone prevents attacks of MS-like illness in laboratory models and has been tested in a number of human trials.
The review summarized here examined human trials including 3233 subjects with MS. However, only 540 subjects with RRMS and 1049 with progressive MS contributed to the primary analyses of treatment efficacy.
Disease progression was not affected by daily GA administration. However, GA did increase the chance that RRMS subjects would be relapse-free at the end of the first year of treatment (Relative Risk 1.3 [95%CI: 1.02-1.6], NNT=8 [95%CI: 4-71]). This effect was not statistically significant at two or three years after treatment. In RRMS patients, GA reduced the number of relapses after 12, 24, and 36 months of treatment and reduced the mean disability score and hospitalization rate. GA had no effect on progressive MS.
Caveats: The benefits of GA as documented in the studies reviewed in this Cochrane analysis are weak, and of questionable importance. Besides, significant heterogeneity existed among the included studies. The implications for real world practice are not clear.
The review showed that GA increases the chance of patients being relapse free at 12 months. Moreover, the relative risk for almost all outcomes trended in the same direction, suggesting that the limited number of subjects studied may have provided inadequate power to show the drugs’ effects.
Although the analysis reported no significant increase (over placebo) in serious side effects, it did show an increase in palpitations, flushing, chest tightness, and anxiety. While these effects were limited to a duration of 30 minutes or less and occurred only in patients who took the injectable form, it should be noted that occurrence of symptoms on a daily basis may be important to patients.
Overall, based on the lack of important harms and small but demonstrable benefits, we have chosen to label this intervention GREEN (benefits outweigh harms). However, we would like to see larger, higher quality studies using placebo controls. We do not believe that GA has been proven effective based on these data. Given the limited available therapeutic options, patients with MS deserve a more definitive answer to the question of how likely it is for this medication to help them.
As of January 2017, the price of the medication ranges between $2500 to 5200 for one carton (30 syringes).
1) Study group event rate:
84/144 (58%, 95% confidence interval [CI]: 50-66%) with RRMS relapse-free at 1 year
2) Control event rate (CER):
65/143 (45%, 95% CI: 38-54%) with RRMS relapse-free at 1 year.
3) Absolute risk increase (ARI):
13% (95% CI: 1-24%) increased chance of being relapse-free at 1 year in patients with RRMS
4) Relative risk of being relapse-free at 1 year for RRMS patients:
1.3 (95% CI: 1.02-1.6)
8 (95% CI 4-71) for being relapse-free at 1 year: for patients with RRMS
Author: Luke Donnelly, MD and Mathew Foley, MD
Department of Emergency Medicine, State University of New York, Downstate Medical Center
Published/Updated: February 1, 2017
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