Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy

Rossella Parini, Paola De Lorenzo, Andrea Dardis, Alberto Burlina, Alessandra Cassio, Paolo Cavarzere, Daniela Concolino, Roberto Della Casa, Federica Deodato, Maria Alice Donati, Agata Fiumara, Serena Gasperini, Francesca Menni, Veronica Pagliardini, Michele Sacchini, Marco Spada, Roberta Taurisano, Maria Grazia Valsecchi, Maja Di Rocco, Bruno Bembi

Research output: Contribution to journalArticle

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Abstract

Background: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. Methods: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Results: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. Conclusions: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

Original languageEnglish
Article number32
JournalOrphanet Journal of Rare Diseases
Volume13
Issue number1
DOIs
Publication statusPublished - Feb 8 2018

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Glycogen Storage Disease Type II
Enzyme Replacement Therapy
Multicenter Studies
Age of Onset
Neuroimaging
Walking
Observational Studies
Ventilation
Disease Progression
Therapeutics
Central Nervous System
Retrospective Studies
History
Clinical Trials

Keywords

  • Alglucosidase alpha
  • ERT
  • Infantile onset Pompe disease
  • Recombinant human GAA
  • rhGAA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. / Parini, Rossella; De Lorenzo, Paola; Dardis, Andrea; Burlina, Alberto; Cassio, Alessandra; Cavarzere, Paolo; Concolino, Daniela; Della Casa, Roberto; Deodato, Federica; Donati, Maria Alice; Fiumara, Agata; Gasperini, Serena; Menni, Francesca; Pagliardini, Veronica; Sacchini, Michele; Spada, Marco; Taurisano, Roberta; Valsecchi, Maria Grazia; Di Rocco, Maja; Bembi, Bruno.

In: Orphanet Journal of Rare Diseases, Vol. 13, No. 1, 32, 08.02.2018.

Research output: Contribution to journalArticle

Parini, R, De Lorenzo, P, Dardis, A, Burlina, A, Cassio, A, Cavarzere, P, Concolino, D, Della Casa, R, Deodato, F, Donati, MA, Fiumara, A, Gasperini, S, Menni, F, Pagliardini, V, Sacchini, M, Spada, M, Taurisano, R, Valsecchi, MG, Di Rocco, M & Bembi, B 2018, 'Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy', Orphanet Journal of Rare Diseases, vol. 13, no. 1, 32. https://doi.org/10.1186/s13023-018-0771-0
Parini, Rossella ; De Lorenzo, Paola ; Dardis, Andrea ; Burlina, Alberto ; Cassio, Alessandra ; Cavarzere, Paolo ; Concolino, Daniela ; Della Casa, Roberto ; Deodato, Federica ; Donati, Maria Alice ; Fiumara, Agata ; Gasperini, Serena ; Menni, Francesca ; Pagliardini, Veronica ; Sacchini, Michele ; Spada, Marco ; Taurisano, Roberta ; Valsecchi, Maria Grazia ; Di Rocco, Maja ; Bembi, Bruno. / Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. In: Orphanet Journal of Rare Diseases. 2018 ; Vol. 13, No. 1.
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abstract = "Background: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. Methods: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Results: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71{\%}) were CRIM-positive. Nineteen patients (67{\%}) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4{\%}) and seven (6 CRIM-positive and one unknown: 25{\%}) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. Conclusions: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.",
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T1 - Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy

AU - Parini, Rossella

AU - De Lorenzo, Paola

AU - Dardis, Andrea

AU - Burlina, Alberto

AU - Cassio, Alessandra

AU - Cavarzere, Paolo

AU - Concolino, Daniela

AU - Della Casa, Roberto

AU - Deodato, Federica

AU - Donati, Maria Alice

AU - Fiumara, Agata

AU - Gasperini, Serena

AU - Menni, Francesca

AU - Pagliardini, Veronica

AU - Sacchini, Michele

AU - Spada, Marco

AU - Taurisano, Roberta

AU - Valsecchi, Maria Grazia

AU - Di Rocco, Maja

AU - Bembi, Bruno

PY - 2018/2/8

Y1 - 2018/2/8

N2 - Background: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. Methods: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Results: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. Conclusions: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

AB - Background: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. Methods: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Results: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. Conclusions: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

KW - Alglucosidase alpha

KW - ERT

KW - Infantile onset Pompe disease

KW - Recombinant human GAA

KW - rhGAA

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