Anaphylaxis and Desensitization to Alglucosidase Alfa in late-onset Pompe Disease ten years later after initial enzyme replacement therapy administration: a possible drug-drug interaction of CGRP inhibiting therapies

Alberto Lerario

Anaphylaxis and Desensitization to Alglucosidase Alfa in late-onset Pompe Disease ten years later after initial enzyme replacement therapy administration: a possible drug-drug interaction of CGRP inhibiting therapies

Autori

ALBERTO LERARIO (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY – NEUROLOGIA)
ELENA ABATI (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY – NEUROLOGIA)
DANIELE VELARDO (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY – NEUROLOGIA)
GIACOMO PIETRO COMI (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY. – NEUROLOGIA)
STEFANIA CORTI (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY – NEUROLOGIA)
MONICA SCIACCO (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY – NEUROLOGIA)

Presentatore

ALBERTO LERARIO (NEUROMUSCULAR AND RARE DISEASE UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, 20122 MILANO, ITALY)

Modalità

Poster Session

Abstract

To date, alglucosidase alfa or avalglucosidase alfa (GAA) enzyme replacement therapies (ERT), are the only approved treatments in Pompe disease, reported to improve or stabilize motor and respiratory function in late-onset forms.
Infusion-associated reactions (IAR) have been reported to span between 18% to 40% of the patients treated in three different studies. In a cohort of 115 French adult patients the median time between ERT initiation and the first IAR was 7.6 months; among these patients, 65.6% experienced their first IAR during the first year of ERT, whereas only two cases after 7 to 9 years after initial administration.
We present the case of a 39-year-old female patient, who was diagnosed with late-onset forms at the age of 29 years and has since then been treated with GAA. During an infusion, she experienced rash, itching and bronchospasm for which she required emergency assistance. The patient, who also suffers from severe migraine, had been started on a therapy with monoclonal antibodies against Calcitonin gene-related peptide (CGRP) less than one month before IAR.
Given the temporal association between monoclonal antibody administration and IAR to GAA we hypothesize the occurrence of an immunological reaction linking sustained CGRP inhibition to the pathological clinical manifestations, also considering her high titer of anti-alglucosidase alfa IgG antibodies and her positivity to anti-thyroglobulin antibodies. CGRP and its receptors are expressed widely throughout the body, and as such there are several theoretical off-target effects of long-term inhibition including regulatory response in systemic inflammation.