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Long-term Experience of Glatiramer Acetate in Treating Multiple Sclerosis


reactivation, but not of disease evidence of rebound (four or five new lesions maximum). Overall, GA was considered to be an effective and safe option for MS patients who are discontinuing natalizumab therapy.


Adherence, Safety, and Tolerability of Glatiramer Acetate Treatment


Studies have indicated that GA has a favorable safety profile compared with the other DMDs for MS. Unlike IFNβ, GA does not cause liver function abnormalities, leukopenia, or thyroid disease and is not associated with depression. The influenza-like symptoms characteristic of IFNβ treatment do not occur with GA.33


GA is the only therapy to be given a category B pregnancy classification, meaning that although no adverse effects have been found in animal studies, no adequate studies have been carried out in pregnant women to demonstrate its safety in humans. Other MS treatments are at least category C or D. A recent prospective study showed that 13 of 14 pregnancies resulted in live births, with GA treatment throughout pregnancy for nine of the women.44


Long-term safety data indicate that adverse effects known to be related to GA therapy are consistent with known side effects of GA administration. These include local injection-site reactions, such as erythema, pain, and lipoatrophy,45,46


and symptoms associated with a


rare self-limited post-injection reaction, which include vasodilatation, chest pain, tachycardia, palpitation, or dyspnea. However, these systemic reactions are transient and self-limited.45,46


There have been


no reported incidents of hematologic, hepatic, or renal dysfunction, immunosuppression, malignancy, or other autoimmune disorders.27


GA


is also the only therapy that does not require any continued laboratory monitoring or further specialist studies. IFNβ administration still requires blood counts, liver functions, and antibody detection.


A recent study in the US aimed to determine the predictors of adherence to GA treatment among 146 patients with MS who were treatment-naive (TN) and 88 who were treatment-experienced (TE).47 During a 12-week treatment period there was no difference between the groups in adherence (86 % in both groups). The predictors of adherence, however, were different. For TN patients these factors were greater functional self-efficacy, higher self-injection competence at baseline, and improvement in self-injection competence over the first month of therapy. For TE patients, the predictors were lower body mass index and longer duration of MS predicted adherence. It was concluded that measures to improve self-efficacy should be taken with TN patients but the predictors for TE patients need more investigation.


The Correlative analyses of adherence in relapsing–remitting MS (CAIR) study is a prospective, web-based, patient-centered, cohort study in the Netherlands. Its primary objective is to investigate whether GA adherence is associated with specific disciplines of care or quantities of specific care. The secondary objective is to investigate whether specific aspects of the socioeconomic situation, healthcare and caregivers, disease, treatment, or patient characteristics impact GA adherence.48


This study is ongoing, with recruitment planned to complete in July 2011 and assessments planned to take place over a 12-month duration.


US NEUROLOGY


Figure 2: Expanded Disability Status Scale Scores in the 15-year Long-term Study of Glatiramer Acetate Therapy


6


0 1 2 3 4 5


*


1


2314 Years on GA therapy


4 5 6 7 8 9 10111213


15


Yearly mean expanded disability status scale (EDSS) scores for ongoing patients (n=100) in the glatiramer acetate (GA) study at the 15-year analysis. The asterisk (*) indicates that the yearly mean EDSS scores for years 14 and 15 are derived from the scores of patients who were originally randomized to GA in the placebo-controlled phase of the study (n=90). SE = standard error. Source: Ford et al., 2010.27


In a recent retrospective claims analysis comparing adherence and persistence among MS patients treated with disease-modifying therapies (DMTs) including GA, patients taking IFNβ-1a had significantly higher adherence compared with other DMTs, possibly owing to the less frequent dosing schedule for IFNβ-1a.49


Economic studies have shown


that improved adherence in MS patients treated with GA compared with other MS drugs results in better outcomes leading to improved cost-effectiveness.50


Analyses of data from large populations of


An analysis of records of a population of 284 patients with MS in the US showed that, during treatment with GA, IFNβ-1a, or IFNβ-1b, only GA was associated with significantly fewer days missed from work due to short-term disability (18.24 fewer days, p<0.03), worker’s compensation (29.50 fewer days, p<0.04), or any reason (53.70 fewer days, p<0.003).54


A study in Europe and the US on a planned population of 1,350 patients with RRMS that aims to evaluate the efficacy of GA given as three weekly 40 mg doses (rather than daily 20 mg doses) versus placebo is currently in progress (A study in subjects with relapsing–remitting multiple sclerosis to assess the efficacy, safety and tolerability of glatiramer acetate injection 40 mg administered three times a week compared to placebo [Glatiramer acetate low-frequency administration; GALA] trial).55


Randomized treatment


will last for 12 months followed by an open-label extension. Recruitment has recently completed and the primary completion date is November 2012. If shown to be effective and safe, three-times-weekly dosing of GA may be a more convenient and tolerable regimen for patients with MS and may consequently improve treatment adherence.


Long-term Studies


The US GA trial has been ongoing since 1991. A total of 232 patients started randomized treatment and received at least one dose of GA. As of February 2008,27


100 patients remained in the open-label extension of this study. Patients enrolled in the extension study have a mean GA 129


MS patients in the US drawn from the Data Mart database has shown that, compared with IFNβ-1a (sc or im) and IFNβ-1b, GA provides improved relapse rate reductions and consequently lower medical costs.51–53


Mean EDSS ± SE


GA start


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