Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy in Pompe disease

To the Editor: In 2001, Genetics in Medicine published an article titled “Recombinant Human Acid α-Glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial.”¹ One of the three patients in that publication (“patient 1”) was recently presented anew in a case report by Banugaria et al.²

The data presented in these two publications are mutually inconsistent. Amalfitano et al.¹ published in 2001 that “patient 1” received recombinant human acid α-glucosidase (rhGAA) in a twice-weekly dose of 5 mg/kg for 14–17 months (63–76 weeks). In contrast, Banugaria et al.² reported that “patient 1” received rhGAA in a twice-weekly dose of 5 mg/kg for only 5 months (22 weeks), followed by a twice-weekly dose of 10 mg/kg over the next 8 months (36 weeks), and a five-times-weekly dose of 10 mg/kg over the last 4 months (17 months in total). Furthermore, the recent case report by Banugaria et al.² revealed that “patient 1” was subjected to three rounds of immunomodulation consisting of cyclophosphamide, intravenous immunoglobulin, plasmapheresis, and increased doses of rhGAA (10 mg/kg daily for 9 days in a row). According to Banugaria et al.,² the three rounds of immunomodulation occurred within the first 13 months (60 weeks) of treatment, but were not reported by Amalfitano et al.¹

On another occasion, Hunley presented a case to the American College of Medical Genetics 2003 Annual Meeting. A publication followed 1 year later.³ On the basis of the age at start of treatment and the gender of the patient, the case presented by Hunley et al.³ very likely referred to “patient 2” in Amalfitano et al.¹ According to Amalfitano et al.,¹ “patient 2” received rhGAA in a twice-weekly dose of 5 mg/kg for 14–17 months, but according to Hunley et al.³ “patient 2” received rhGAA in a twice-weekly dose of 5 mg/kg for only 15 weeks (3.3 months), followed by a twice-weekly dose of 10 mg/kg during the next 27 weeks (11 months), and a five-times-weekly dose of 10 mg/kg over the last 11 weeks (2.5 months) (17 months in total). Furthermore, Hunley’s case report³ revealed that “patient 2” underwent experimental immune tolerance therapy beginning after 24 weeks (5.3 months) of treatment for 10 days, which consisted of frequent plasmapheresis and intravenous immunoglobulin G administration, with daily infusions of rhGAA (10 mg/kg body weight) and cyclophosphamide. As with “patient 1,” none of these interventions were mentioned in the article published in Genetics in Medicine.¹

Disclosure

Erasmus MC and its inventors of methods to produce recombinant human acid α-glucosidase for treatment of Pompe disease receive royalties and provide consultancy to Genzyme Corporation (Cambridge, MA) pursuant to an agreement between Genzyme Corporation and Erasmus MC.