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 journalArticlepeer-review


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
Issue number5
Publication statusPublished - Jan 1 2019


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

ASJC Scopus subject areas

  • Pharmacology (medical)


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