COVID-19 ERT Interruptions Caused Worse Motor, Respiratory Symptoms

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Interruptions to Myozyme enzyme replacement therapy (ERT) regimens during the COVID-19 pandemic led to worsened motor symptoms and poorer respiratory function in patients with Pompe disease, a French study found.

These decreases in motor and respiratory function — seen after just a couple of months — were not immediately restored when treatment was restarted, according to researchers.

“It is important to note that the worsening was rapid and not reversible 3 months later, after ERT restart,” the investigators wrote, noting that the treatment interruptions also caused “significant” losses in function among individual patients.

The study, “Motor and respiratory decline in patients with late onset Pompe disease after cessation of enzyme replacement therapy during COVID-19 pandemic,” was published in the European Journal of Neurology.

Patients with late-onset Pompe disease (LOPD) being treated with ERT are at increased risk of developing severe forms of COVID-19.

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These patients have weakness in the diaphragm — a muscle responsible for helping the lungs expand and contract during normal breathing — as well as lower respiratory tract infections that raise the risk of acute deterioration. Also, the limited availability of face masks and the hospitalizations to be treated with ERT also made patients susceptible to being infected with SARS-CoV2, the virus that causes COVID-19.

ERT with Lumizyme (alglucosidase alfa), known as Myozyme in Europe, has been shown to improve motor function and respiratory function. However, data on the impact of stopping ERT are scarce.

During the pandemic, the French neuromuscular network chose to continue ERT with Myozyme at home in certain instances, when home hospitalization was possible or when patients were in trials for new therapies. But for most patients, their clinicians and centers hypothesized that a suspension of ERT would not lead to symptom worsening, and that the risk-benefit analysis was favorable.

Now, French scientists evaluated the effects of Myozyme suspension due to the pandemic on the symptoms of 31 LOPD patients from the French Pompe Registry.

The patients had a mean age of 40.5 at diagnosis, and 47 at the beginning of Myozyme treatment. The mean age at the time of ERT interruptions was 55 years. Overall, the patients had been treated for 86.5 months, or more than seven years, with a range of four to 160 months (13.3 years) on ERT.

Overall, the duration of ERT suspension was 2.2 months. Among the participants, 21 (68%) reported regular physiotherapy before stopping treatment (baseline) versus 16 patients (52%) at the time when Myozyme was restarted following the interruption.

During the ERT interruptions, 12 patients (31%) practiced self-rehabilitation using exercises provided on the website of the French national network for neuromuscular diseases.

At the time of ERT interruptions, the patients’ median forced vital capacity (FVC) — how much air a person can exhale forcibly after a deep breath — was 62%, as compared with a normal FVC of at least 80%.

During Myozyme interruptions, FVC while sitting was decreased significantly from 2.81 L before ERT to 2.45 L. It was 2.55 L after ERT restart.

Similar to FVC, motor function — assessed with the 6-minute walk test, a standard test of mobility — worsened significantly after ERT stop and did not normalize with treatment restart.

“There were also significant functional losses at the individual level, on which we cannot present statistical data; some patients, for instance, were able to climb four steps and lost this capacity, which was not recovered at 3 months after ERT restart,” the researchers wrote.

They also noted that the decreased respiratory and motor function after ERT discontinuation shown in this study suggests that this therapy, in fact, slows down Pompe disease progression.

“This national study based on data from the Pompe Registry shows that the interruption of ERT, even as short as only few months, worsens LOPD patients motor and respiratory function,” the researchers concluded.

Of note, the Pompe Registry is financed by Sanofi Genzyme, which markets Lumizyme/Myozyme.