Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group

Massimiliano Filosto, Stefano Cotti Piccinelli, Sabrina Ravaglia, Serenella Servidei, Maurizio Moggio, Olimpia Musumeci, Maria Alice Donati, Elena Pegoraro, Antonio Di Muzio, Lorenzo Maggi, Paola Tonin, Gianni Marrosu, Cristina Sancricca, Alberto Lerario, Michele Sacchini, Claudio Semplicini, Virginia Bozzoni, Roberta Telese, Silvia Bonanno, Rachele PirasMaria Antonietta Maioli, Giulia Ricci, Liliana Vercelli, Anna Galvagni, Serena Gallo Cassarino, Filomena Caria, Tiziana Mongini, Gabriele Siciliano, Alessandro Padovani, Antonio Toscano

Research output: Contribution to journalArticle

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Abstract

Introduction: Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. Methods: We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. Results: Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. Conclusion: Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

Original languageEnglish
Pages (from-to)1177-1189
JournalAdvances in Therapy
Volume36
Issue number5
DOIs
Publication statusPublished - Jan 1 2019

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Glycogen Storage Disease Type II
Enzyme Replacement Therapy
Antibodies
Late Onset Disorders
Vital Capacity
Gait
Walking

Keywords

  • Anti rh-GAA antibodies
  • Glycogen storage diseases II
  • GSD II
  • LOPD
  • Pompe disease

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group. / Filosto, Massimiliano; Cotti Piccinelli, Stefano; Ravaglia, Sabrina; Servidei, Serenella; Moggio, Maurizio; Musumeci, Olimpia; Donati, Maria Alice; Pegoraro, Elena; Di Muzio, Antonio; Maggi, Lorenzo; Tonin, Paola; Marrosu, Gianni; Sancricca, Cristina; Lerario, Alberto; Sacchini, Michele; Semplicini, Claudio; Bozzoni, Virginia; Telese, Roberta; Bonanno, Silvia; Piras, Rachele; Maioli, Maria Antonietta; Ricci, Giulia; Vercelli, Liliana; Galvagni, Anna; Gallo Cassarino, Serena; Caria, Filomena; Mongini, Tiziana; Siciliano, Gabriele; Padovani, Alessandro; Toscano, Antonio.

In: Advances in Therapy, Vol. 36, No. 5, 01.01.2019, p. 1177-1189.

Research output: Contribution to journalArticle

Filosto, M, Cotti Piccinelli, S, Ravaglia, S, Servidei, S, Moggio, M, Musumeci, O, Donati, MA, Pegoraro, E, Di Muzio, A, Maggi, L, Tonin, P, Marrosu, G, Sancricca, C, Lerario, A, Sacchini, M, Semplicini, C, Bozzoni, V, Telese, R, Bonanno, S, Piras, R, Maioli, MA, Ricci, G, Vercelli, L, Galvagni, A, Gallo Cassarino, S, Caria, F, Mongini, T, Siciliano, G, Padovani, A & Toscano, A 2019, 'Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group', Advances in Therapy, vol. 36, no. 5, pp. 1177-1189. https://doi.org/10.1007/s12325-019-00926-5
Filosto, Massimiliano ; Cotti Piccinelli, Stefano ; Ravaglia, Sabrina ; Servidei, Serenella ; Moggio, Maurizio ; Musumeci, Olimpia ; Donati, Maria Alice ; Pegoraro, Elena ; Di Muzio, Antonio ; Maggi, Lorenzo ; Tonin, Paola ; Marrosu, Gianni ; Sancricca, Cristina ; Lerario, Alberto ; Sacchini, Michele ; Semplicini, Claudio ; Bozzoni, Virginia ; Telese, Roberta ; Bonanno, Silvia ; Piras, Rachele ; Maioli, Maria Antonietta ; Ricci, Giulia ; Vercelli, Liliana ; Galvagni, Anna ; Gallo Cassarino, Serena ; Caria, Filomena ; Mongini, Tiziana ; Siciliano, Gabriele ; Padovani, Alessandro ; Toscano, Antonio. / Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group. In: Advances in Therapy. 2019 ; Vol. 36, No. 5. pp. 1177-1189.
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T1 - Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group

AU - Filosto, Massimiliano

AU - Cotti Piccinelli, Stefano

AU - Ravaglia, Sabrina

AU - Servidei, Serenella

AU - Moggio, Maurizio

AU - Musumeci, Olimpia

AU - Donati, Maria Alice

AU - Pegoraro, Elena

AU - Di Muzio, Antonio

AU - Maggi, Lorenzo

AU - Tonin, Paola

AU - Marrosu, Gianni

AU - Sancricca, Cristina

AU - Lerario, Alberto

AU - Sacchini, Michele

AU - Semplicini, Claudio

AU - Bozzoni, Virginia

AU - Telese, Roberta

AU - Bonanno, Silvia

AU - Piras, Rachele

AU - Maioli, Maria Antonietta

AU - Ricci, Giulia

AU - Vercelli, Liliana

AU - Galvagni, Anna

AU - Gallo Cassarino, Serena

AU - Caria, Filomena

AU - Mongini, Tiziana

AU - Siciliano, Gabriele

AU - Padovani, Alessandro

AU - Toscano, Antonio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. Methods: We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. Results: Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. Conclusion: Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

AB - Introduction: Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. Methods: We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. Results: Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. Conclusion: Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

KW - Anti rh-GAA antibodies

KW - Glycogen storage diseases II

KW - GSD II

KW - LOPD

KW - Pompe disease

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