Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long‐term clinical outcome of classic infantile Pompe patients

Abstract

The aim of this study was to compare the long-term outcome of classic infantile Pompe patients treated with 20 mg/kg alglucosidase alfa every other week (eow) to those treated with 40 mg/kg/week, and to study the additional effect of immunomodulation. Six patients received 20 mg/kg eow and twelve 40 mg/ kg/week. Five patients were cross-reactive immunologic material (CRIM)-negative, two in the 20 mg, three in the 40 mg group. We compared (ventilatorfree) survival, motor outcome, infusion associated reactions (IARs), and antibody formation. From 2012 on patients >2 months in the 40 mg group also received immunomodulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in an enzyme replacement therapy (ERT)-naïve setting. Survival was 66% in the 20 mg group and 92% in the 40 mg group. Ventilator-free survival was 50% and 92%. Both CRIM-negative patients in the 20 mg group died, whereas all three are alive in the 40 mg group. In the 20 mg group, 67% learned to walk compared with 92% in the 40 mg group. At the age

Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease

“…The proportion of patients with a (very) high peak titer in our study is comparable to what we previously reported in adult patients (23% vs. 22%) [ 14 ]. We found high sustained antibody titers in only one patient (with short follow up duration), which is also comparable to adults, but in contrast to what is reported in classic infantile Pompe disease patients, especially in CRIM negative patients [ 13 , 22 ]. We postulated that lower endogenous α-glucosidase activity may lead to higher antibody titers, which was previously hypothesized in adults too [ 14 ].…”

“…Patient 1 was only 1 year old when ERT was started, therefore assessment of the MRC, QMFT and FVC could not be performed during the first years of treatment. The motor domain of the Bayley Scales of Infant Development-II (BSID-II), which is a tool for developmental assessment in the first 2 years of life, showed a delayed motor development at start of ERT (BSID-II SD score < − 3.0) [ 22 ]. During the first 2 years of treatment, the BSID-II improved to SD scores between − 1.7 and − 0.6, which are age-equivalent scores, reflecting normal development (Additional file 1 : Table S3).…”

“…Moreover, also adult Pompe patients can develop antibodies against rhGAA that interfere with treatment efficacy [ 15 , 16 ]. Other factors that have been described to influence antibody formation in classic infantile Pompe patients are dosing of rhGAA and age of treatment initiation [ 12 , 22 , 26 , 27 ]. Contrary to what was previously reported, we did not observe development of high antibody titers in any of the patients treated with a higher dose (> 20 mg/kg/every other week) [ 22 , 26 ].…”

“…Other factors that have been described to influence antibody formation in classic infantile Pompe patients are dosing of rhGAA and age of treatment initiation [ 12 , 22 , 26 , 27 ]. Contrary to what was previously reported, we did not observe development of high antibody titers in any of the patients treated with a higher dose (> 20 mg/kg/every other week) [ 22 , 26 ]. This applied for patients treated with a higher dose (40 mg/kg/week) from start of treatment, as well as for patients who later switched to a higher dose of rhGAA.…”

Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus

“…ERT may be started in patients with typical cardiorespiratory symptoms if the enzyme is deficient in DBS, even before seeing the genetic result ( 52 ). The usual recommended dose is 20 mg/kg alglucosidase alfa every other week; however, a recent study showed that patients treated with higher doses and more frequent injections had a better outcome such as motor, respiratory, and biochemical markers ( 53 , 54 ).…”