Managing adults with Pompe disease requires a deep understanding of long-term enzyme replacement therapy (ERT). While most patients benefit, the formation of anti-recombinant human acid α-glucosidase (rhGAA) antibodies can complicate treatment. This research provides critical insights into how these antibodies affect Pompe disease enzyme replacement efficacy and safety over several years.

The study monitored 111 adult patients to track antibody titres and clinical metrics. Researchers specifically looked at the six-minute walk test (6MWT) and forced vital capacity (FVC). Interestingly, nearly 30% of the participants developed high peak antibody titres. Consequently, these individuals faced a significantly higher risk of infusion-associated reactions (IARs).

Long-Term Clinical Efficacy of Pompe Disease Enzyme Replacement

Moreover, the study explored whether high antibody levels hinder physical performance. At a group level, high titres did not appear to diminish the clinical benefits of Pompe disease enzyme replacement. Surprisingly, patients with high peak titres maintained more stable lung function compared to those with low or intermediate levels. However, nine patients exhibited neutralising activity which could negatively influence individual disease progression.

Furthermore, the data suggests that while high sustained antibody titres (HSAT) correlate with increased IARs, they do not uniformly predict clinical decline. Clinicians should therefore continue to monitor antibody status to personalize treatment strategies. This approach ensures that individual patients who may be negatively impacted receive appropriate clinical attention.

Frequently Asked Questions

Do antibodies always reduce the efficacy of Pompe disease enzyme replacement?

No, high antibody titres do not significantly impact clinical outcomes like walking distance or lung function at a group level. However, they can negatively affect the disease course in specific individuals, especially if neutralising activity is present.

What are the main risks associated with high anti-rhGAA antibodies?

The primary risk identified is an increased frequency of infusion-associated reactions (IARs). Patients with high titres are significantly more likely to experience these reactions compared to those with lower antibody levels.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a substitute for professional healthcare. Refer to the latest local and national guidelines for clinical practice.

References

1. Theunissen MTM et al. Antibody formation and efficacy of enzyme replacement therapy in adults with Pompe disease: Unlocking long-term insights. Genet Med. 2026 Apr 13. doi: undefined. PMID: 41979053.

2. van der Ploeg AT, et al. A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe’s Disease. N Engl J Med. 2010;362(15):1396-1406.

3. Schoser B, et al. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol. 2017;264(4):621-630.