In this study, immunomodulatory treatment of relapsing-remitting multiple sclerosis with glatiramer acetate was associated with a reduction in subjective perceptions of fatigue and with the numbers of days taken off work due to illness. We observed a reduction of approximately one-quarter in both MFIS scores and in a VAS measure of fatigue. These findings are consistent with an earlier retrospective study, which also reported an improvement in fatigue measured with the FIS following initiation of glatiramer acetate treatment in 24.8% of patients . The two studies cannot, however, be directly compared due differences in methodology.
The amelioration observed following treatment with glatiramer acetate may be a non-specific consequence of improved overall disease status in treated patients or alternatively result from a specific action of the medication on the pathophysiology of multiple sclerosis fatigue. For example, it has been suggested that fatigue may be aggravated by the production of high levels of pro-inflammatory cytokines [26, 27]. The ability of glatiramer acetate to attenuate the secretion and activity of these cytokines within the central nervous system [28, 29] may provide such a specific mechanism. Others have proposed, on the basis of magnetic resonance spectroscopy (MRS) findings, that fatigue may be associated with axonal injury in the cortex rather than inflammatory white matter lesions per se . In a recent trial, Tedeschi et al. could demonstrate that among MS patients with low disability those with high-fatigue show higher white and gray matter atrophy and higher lesion load. They suggest that in MS, independent of disability, white and gray matter atrophy is a risk factor to have fatigue . In additon, a recent trial of Rocca et al. using functional imaging in MS patients with fatigue and interferon beta-1a treatment pointed out that an abnormal recruitment of the fronto-thalamic circuitry is associated with interferon-induced fatigue in MS patients . In contrast to the interferon's, the specific action of glatiramer acetate to improve MRS markers of axonal injury in multiple sclerosis might contribute to a reduction in fatigue [33, 34].
We also observed a dramatic reduction of over fifty percent in the number of patients who needed to take time off work due to their multiple sclerosis. This is consistent with findings from an American study, which also reported a marked decrease in days off work in patients treated with glatiramer acetate , but less so with beta-interferons. This is an important functional effect of treatment since the ability to hold down a job satisfactorily is critical for self-esteem and because, in certain countries such as the USA, remaining in full-time employment is an important determinant of obtaining insurance for reimbursement of treatment costs.
Again, the impact of glatiramer acetate on time off work may be an indirect consequence of reduced relapse frequency, although the data from the US study showing a differential effect on time off work between glatiramer acetate and β-interferons would argue against this. Alternatively, the observed effect may be secondary to a reduction in fatigue, which has been identified in other studies to be a major reason why patients with multiple sclerosis need to take time off work [11, 12]. Finally, it should be noted that the low incidence of debilitating side-effects reported with glatiramer acetate  means that patients are unlikely to need to take time off work due to treatment side-effects.
The strength of this study include the naturalistic design, which means that the findings can probably be generalised to standard care, at least in Europe, with confidence, the prospective nature of the data collection and the relatively large numbers of patients evaluated. Limitations include the absence of a comparator group against which the magnitude of the observed treatment effects could be assessed, and data collection during physician consultations rather than with patients' diaries, which may have introduced some degree of anamnestic error into the findings. The absence of a control group might overestimate the improvement in fatigue symptoms. As a placebo group is probably not ethical it will be further of interest to compare prospectively the benefit on fatigue in a group of naive MS patients treated with GA vs. a group treated with IFN-beta in a next study.