Long-term ERT Use Can Help Older Adults With LOPD, Study Finds
Long-term treatment with Myozyme (alglucosidase alfa) — marketed in the U.S. as Lumizyme — results in variable but satisfactory motor and respiratory outcomes among older adults recently diagnosed with late-onset Pompe disease (LOPD), a study from Germany reported.
According to its researchers, these findings were similar overall to studies of Myozyme in younger patient groups, suggesting this treatment’s start in LOPD patients after age 50 is also justified.
The study, “Long-term effects of enzyme replacement therapy in an elderly cohort of late-onset Pompe disease,” was published in Neuromuscular Disorders.
Pompe disease is characterized by the accumulation of glycogen, a sugar molecule, in cells due to a dysfunctional or missing GAA enzyme. Myozyme, an enzyme replacement therapy (ERT) marketed by Sanofi Genzyme, gives patients a purified form of GAA to help avoid glycogen buildup and slow disease progression.
Previous research showed that Myozyme improves symptoms in the first years of treatment, but declines in effectiveness over time. Changes in muscle strength, walking ability and lung function are noted.
To evaluate the long-term effects of Myozyme in older LOPD patients, researchers at the University Hospital of Bonn retrospectively analyzed clinical and laboratory data from six LOPD patients — three men and three women, diagnosed at a median age of 63 — who had been on ERT for at least seven years.
All had the same mutation in their GAA gene, which is responsible for making the GAA enzyme. All six patients also began biweekly Myozyme infusions immediately after their diagnosis.
Walking ability, muscle function, and lung capacity were measured in patients at baseline — around the time of diagnosis — and at regular intervals over the course of eight to 12 years.
At treatment start, all were able to walk independently. Between one and four years later, four out of six patients required the use of a walking aid, either a walker or a cane. Two of these individuals later needed a wheelchair.
Study findings showed that walking ability — measured by the six-minute walk test (6MWT) — generally improved over time. Initially, patients walked a median of 281 meters (about 922 feet), which increased to a median of 307 meters by the final measure (after eight to 12 years of ERT), with four of six showing an overall improvement.
A decline over time was noted in the remaining two patients, before the use of a wheelchair prevented further testing.
In contrast, one patient showed an overall improvement in the quick motor function test (QMFT), a measure of motor performance for Pompe patients. QMFT performance generally declined across the group, going from a median of 57.1% at baseline to 40.6% in final measurements. (A higher percentage on the QMFT indicates better motor performance.)
Overall, muscle strength and lung capacity also declined in the long term.
Muscle strength — measured by the Medical Research Council (MRC) grading scale — fell from a median 82.15% to 71.6% over time, indicating an overall loss of muscle strength, but no individual patient showed a continuous decline.
Forced vital capacity (FVC) was used to quantify lung function, with a higher FVC percentage indicating better function. The test can be administered when the participant is seated or lying down (supine).
Sitting FVC declined from an initial median of 75.2% to 60% over eight years. All six patients showed eventual losses in lung function across the study’s years, individually ranging from a 3.2% to 51.6% overall decline.
Similar trends were observed for supine FVC, however, two patients were able to stabilize or improve over time in this position.
These motor and lung function data may be difficult to interpret because little is known about how aging affects the same measures in people without LOPD, the researchers noted.
“Unfortunately, [age-matched] comparative long-term natural history data on motor and respiratory functions is lacking in LOPD, especially in the elderly,” they wrote.
In diagnostic laboratory tests, skeletal muscle biopsies in five patients showed the glycogen accumulation characteristic of Pompe disease. Lower GAA enzyme activity and higher levels of creatine kinase (CK) — which indicates muscle damage — were also observed at diagnosis. By the final follow-up, their CK levels had fallen to near normal levels.
Over the course of treatment, five out of the six participants developed antibodies against the Myozyme treatment, with women showing the highest antibody levels.
Previous studies on infantile-onset Pompe disease have suggested that higher antibody levels may predict a worse response to treatment. In this study, however, the two patients with the best clinical improvement also had the highest antibody levels.
Ultimately, none of the laboratory measures correlated with clinical outcomes.
“Our data underline that the various diagnostic parameters … do not allow any conclusions to be drawn on the predicted clinical long-term outcome of ERT,” the researchers wrote.
Similar responses to ERT use by older LOPD patients were reported, with overlap to those previously observed in younger patients.
“Interestingly, despite the higher ages and longer disease courses ERT responses were comparable to those previously described in younger patient cohorts. From this, it can be concluded that the treatment in older LOPD patients is equally indicated and justified,” the researchers wrote.
“In conclusion, advanced ages at onset and ages at diagnosis, but also advanced disease stages as shown by the severity of different diagnostic findings should not lead to a more restrictive indication to ERT,” they added.
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