This study describes a large cohort of adult Pompe patients receiving treatment with alglucosidase alfa. It reflects a unique situation in which most patients were also prospectively followed before starting therapy, thereby extending median follow-up to 3 years (14 months before starting ERT and 23 months afterwards). We found that ERT significantly altered the natural course of disease in adult Pompe patients. Muscle strength increased significantly after they started ERT, and FVC in upright position stabilized. Even though, at group level, FVC in supine position and muscle function did not improve during ERT, there were improvements in certain subgroups of patients.
Like previous studies, we found that muscle strength deteriorated significantly before the start of therapy [10, 11] However, the improvement in muscle strength after the start of ERT was greater than that reported in other studies [25–27, 29, 41]. There may be various reasons for this. Our study was restricted to adult patients, but included patients across the entire disease spectrum. We tested more muscle groups, included more patients, and followed a longer treatment period than other studies, thereby producing over 500 measurements in total.
One new finding of this study is that women benefit more from ERT with respect to muscle strength than males. At the same dosage of 20 mg/kg bodyweight, it is possible that the relative dose of alglucosidase alfa received per gram of muscle-fiber tissue is higher in women than in men. Men generally have a higher lean body mass than women, and thus a somewhat higher muscle mass per kg . As women also have smaller muscle fibers than men, they have a higher ratio of muscle-fiber surface to muscle-fiber volume. Consequently, they may have relatively more mannose 6-phosphate surface receptors, which mediate the uptake of alglucosidase alpha [42, 43]. Other factors that may underlie the greater benefit women derive from ERT include muscle-fiber types, activity patterns, and hormonal influences.
Our study did not incorporate the six-minute walk test, a measure of functional endurance used in other studies [24, 27, 29]. Instead, we assessed motor skills related to daily activities, using the QMFT, which was recently validated for use in patients with Pompe disease . Although there was no change in muscle function across the entire group, there were significant improvements in wheelchair-independent patients and those with less pronounced muscle weakness. This finding indicates that timely intervention with ERT may be crucial to improving muscle function. The same is suggested by the results of the subgroup analysis in the trial of late-onset patients .
The stabilization of FVC in upright position in our patients was similar to that recorded in the trial and in other studies; [24–27, 29] the decline in FVC before ERT was similar to that observed in the placebo arm of the trial and natural course studies [10, 11, 13, 29].
This is the first study to report on the effect of ERT on the FVC in supine position. In the whole study population, this measure continued to deteriorate despite ERT, but individual results showed an improvement in almost two-thirds of patients. Patients were more likely to improve if they were younger, were independent of artificial ventilation, had a better FVC in upright position, and had less severe muscle weakness at the start of treatment. Again, this suggests that starting ERT early in the disease course may be beneficial.
Because ERT has been available since 2006, we performed an open-label study rather than a clinical trial, assessing the effect of ERT in all adult patients – from mild to severely affected – for many of whom we had also collected pre-treatment data prospectively. As this is an observational study, we could not correct for residual confounding. The small sample size inherent to rare disorders meant that we could not apply a full multivariate model to identify prognostic factors.