Pre/post effectiveness evaluation of updated additional risk minimisation measures for an orphan disease: Myozyme (alglucosidase alfa) Safety Information Packet.

BACKGROUND: The alglucosidase alfa (Myozyme®) Safety Information Packet ("previous SIP") was updated to improve readability and content ("updated SIP"). We compared the previous and updated SIPs. METHODS: A two-wave pre-post multicountry survey was conducted among health care professionals (HCPs) who prescribed or monitored patients on alglucosidase alfa in the largest European Union ("EU5") countries and Poland. Wave (W) 2 started 15 months after completion of W1 and the implementation of the updated SIP. Changes between the waves were analysed. RESULTS: Forty-six HCPs (34 physicians/12 nurses) participated in W1 and 52 in W2 (42 physicians/10 nurses); 22 participated in both waves. Nonsignificant differences were observed between waves 1 and 2 for awareness (75.6% in W1 and 82.4% in W2) and receipt (77.7% in W1 and 74.5% in W2) of the SIP, reading (88.6% in W1 and 89.5% in W2) and usage (88.2% in W1 and 89.5% in W2) among receivers of the SIP, or the overall knowledge about immunological testing (61.1% in W1 vs 55.1% in W2). Frequency of performance of immunological testing was significantly higher in W2 than in W1 (50.3% vs 34.4%; P = .024) with a tendency for increases in the appropriate performance of all types of testing in W2. CONCLUSIONS: Both versions of the SIP showed relatively high awareness, receipt, reading, and usage, with an overall trend for most measures to improve numerically in W2. The updated SIP did not require further changes.

Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease.

PURPOSE: High sustained antibody titers complicate many disorders treated with a therapeutic protein, including those treated with enzyme replacement therapy, such as Pompe disease. Although enzyme replacement therapy with alglucosidase alfa (Myozyme) in Pompe disease has improved the prognosis of this otherwise lethal disorder, patients who develop high sustained antibody titers to alglucosidase alfa enter a prolonged phase of clinical decline resulting in death despite continued enzyme replacement therapy. Clinically effective immune-tolerance induction strategies have yet to be described in the setting of an entrenched immune response characterized by high sustained antibody titers, wherein antibody-producing plasma cells play an especially prominent role. METHODS: We treated three patients with infantile Pompe disease experiencing marked clinical decline due to high sustained antibody titers. To target the plasma cell source of high sustained antibody titers, a regimen based on bortezomib (Velcade) was used in combination with rituximab, methotrexate, and intravenous immunoglobulin. RESULTS: The treatment regimen was well tolerated, with no obvious side effects. Patient 1 had a 2,048-fold, and patients 2 and 3 each had a 64-fold, reduction in anti-alglucosidase alfa antibody titer, with concomitant sustained clinical improvement. CONCLUSION: The addition of bortezomib to immunomodulatory regimens is an effective and safe treatment strategy in infantile Pompe disease, with potentially broader clinical implications.

Body composition analysis in late-onset Pompe disease.

Pompe disease is an inherited metabolic disorder caused by α-glycosidase deficiency. The adult onset form is mainly characterized by progressive proximal muscle weakness and respiratory dysfunction. The aim of the present study is to evaluate body composition in adult patients before and after enzyme replacement therapy (ERT). Body composition was examined at baseline by means of dual x-ray absorptiometry (DXA) in nine adult patients and after different time periods in six of them who received ERT. Total BMD (bone mineral density) was initially mildly decreased in two patients, while femoral neck BMD was decreased in five patients. On the other hand fat mass was increased in the majority of patients, while body mass index (BMI) was high in four. ERT administration did not seem to induce obvious BMD changes in any patient. Conclusively, the greater femoral neck BMD involvement may be attributed to the lower mechanical load applied by the selectively weakened muscles, whereas the increased fat mass may be the result of metabolic and nutritional derangement.

Glycogen storage disease types I and II: treatment updates.

Prior to 2006 therapy for glycogen storage diseases consisted primarily of dietary interventions, which in the case of glycogen storage disease (GSD) type II (GSD II; Pompe disease) remained essentially palliative. Despite improved survival and growth, long-term complications of GSD type I (GSD I) have not responded to dietary therapy with uncooked cornstarch or continuous gastric feeding. The recognized significant risk of renal disease and liver malignancy in GSD I has prompted efforts towards curative therapy, including organ transplantation, in those deemed at risk. Results of clinical trials in infantile Pompe disease with alglucosidase alfa (Myozyme) showed prolonged survival reversal of cardiomyopathy, and motor gains. This resulted in broad label approval of Myozyme for Pompe disease in 2006. Furthermore, the development of experimental therapies, such as adeno-associated virus (AAV) vector-mediated gene therapy, holds promise for the availability of curative therapy in GSD I and GSD II/Pompe disease in the future.