We observed a mean increase in HR-QoL in treatment-naïve RRMS patients 6 months after start of GA treatment, that was sustained at 12 months. Both mean and median HR-QoL values were higher than at baseline, suggesting that the increase was a group phenomenon, rather than caused by individual outliers. HR-QoL increase was paralleled by a decrease in experienced fatigue, whereas levels of depressed mood remained unchanged.
In a single-centre study Lily et al. assessed HR-Qol in 210 RRMS patients before and during treatment with disease modifying drugs (DMD) - intramuscular (IM) INFb-1a, subcutaneous INFb-1a, subcutaneous INFb-1b, GA - and found that DMD treatment was associated with an increase in HR-QoL : Mean HR-QoL score increased significantly at one month, further increasing to a peak at nine months, and remaining significantly elevated at three years. The small number - eight - of GA-treated patients in their study did not allow for conclusions with respect to GA. Our data show that increase in HR-QoL is also specifically associated with GA treatment. Moreover, our finding that HR-QoL was increased at 6 months and remained elevated at 12 months is in agreement with the pattern described by Lily et al. .
It has been known that the relationship between disability and HR-QoL in MS is complex . In treatment-naive patients we observed an improvement of mean disability score (GNDS) at 6 months, but not at 12 months. In their study Lily et al. found no significant change in median disability (EDSS) throughout the three year study period . Likewise, we found that disability remained unchanged in RRMS patients during two years of treatment with IM INFb-1a, whereas mean physical and mental HR-QoL scores (MS54-QoL) improved significantly . In fact, as prevention of disability progression is a primary goal of DMD treatment, staying clinically stable is per se a beneficial phenomenon. Patients may experience stability as a relative improvement, that positively affects HR-QoL.
No baseline characteristic was predictive of HR-QoL increase, except for low HR-QoL. In contrast, in a study in IM INFb-1a-treated RRMS patients it was found that increase in HR-QoL was associated with young age and low baseline disability . Lily et al. performed multiple regression analysis of baseline characteristics against change in HR-QoL score over the first two years of treatment with DMD . There was no relationship with age, disease duration, disability or number of relapses, and - similar to out finding - the only significant variable predicting a good QoL response was low QoL . In all, age, disease duration, disability, fatigue or depressed mood are characteristics that are not helpful in selecting patients for GA treatment in terms of QoL improvement.
After 12 months treatment-naive patients showed a mean increase in LMS-QoL score of about 11%. It is not known what change in HR-QoL is relevant for individual MS patients. In general, changes of 10% to 15% in clinical outcomes may be considered meaningful. We choose a minimum of 15% of the mean baseline LMS-QoL score in the total population (19.51), being 3 points, for an individual change to be qualified as improvement or worsening. Thus, after one year 4 out of 10 treatment-naive patients had an improved HR-QoL and only 1 out of 10 a worsened HR-QoL. In patients who had completed 12 months treatment changes were even more advantageous, whereas for non-completers mean changes were close to zero or even negative. As most patients who discontinued GA did so because of side effects (73%), in non-completers the negative impact of side effects on HR-QoL may have outweighed GA's positive effect . Moreover, treatment discontinuation could have prevented the full development of GA's beneficial effect, as it is known that relapse reduction occurs not sooner than after 6 months.
Interestingly, in patients with prior immunomodulation/immunosuppression mean HR-QoL did not change significantly. This could be explained by several factors. First, overrepresentation in this group of patients with more active inflammation, as it is likely that a substantial number of patients had stopped previous treatment for reason of incomplete response. In spite of prior treatment, pre-study relapse rate in this group was similar to that in naive patients and on-study relapse rate seemed even higher. Second, the placebo effect was perhaps more modest in this group, as patients had had the disappointing experience of treatment failure, although we think it unlikely that at 12 months a significant placebo effect was still at work in either group. Third, unchanged HR-QoL may relate to the higher rate of non-completers in this group (36%).
At 12 months treatment-naive patients showed a significant decrease in fatigue. Decreased fatigue in MS patients during the first year of GA treatment has been reported by others [3, 4]. Our observation that a decrease in fatigue was associated with an increase in HR-QoL suggests that a decline in experienced fatigue contributes to HR-QoL improvement.
Our study does not inform on HR-QoL beyond the first year of GA treatment. Comparison with the report by Lily et al. shows a similar pattern of early increase in the first 6 months, that is sustained at 12 months, which suggests that this early gain in HR-QoL may be sustained further . Yet, future studies are needed to establish the long-term change in HR-QoL during GA treatment.
In order to weigh expected benefits against risks patients need quantified information on effectiveness before deciding to start DMD treatment. Randomized controlled trials (RCTs) investigate efficacy and mostly do not include overall or patient-centred measures. Moreover, RCT data are obtained in settings not representative of daily practice and thus difficult to generalize. Observational data obtained in 'real-life' are more informative on a patient's chance to reach a pre-defined therapeutic goal. As our patients were treated in daily care settings, this study's results may be considered representative of GA treatment in real life.