Two-Hour CGRP Infusion Causes Gastrointestinal Hyperactivity: Possible Relevance for CGRP Antibody Treatment
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Two-Hour CGRP Infusion Causes Gastrointestinal Hyperactivity : Possible Relevance for CGRP Antibody Treatment. / Falkenberg, Katrine; Bjerg, Helene Rønde; Olesen, Jes.
I: Headache, Bind 60, Nr. 5, 2020, s. 929-937.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Two-Hour CGRP Infusion Causes Gastrointestinal Hyperactivity
T2 - Possible Relevance for CGRP Antibody Treatment
AU - Falkenberg, Katrine
AU - Bjerg, Helene Rønde
AU - Olesen, Jes
PY - 2020
Y1 - 2020
N2 - Objective: The monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are new antimigraine drugs from which many patients already benefit. Very few side effects have been reported from the antibody trials, including very few gastrointestinal (GI) side effects. The current data derive from a double-blind cross-over study of CGRP infusion for 2 hours. We present the GI side effects of the infusion and raise the question if underreporting of GI symptoms in CGRP antibody trials has occurred. We also discuss why constipation may be more likely with CGRP receptor blockade than with CGRP neutralizing antibodies. Methods: Thirty healthy volunteers were recruited to receive a 2-hour infusion of CGRP 1.5 µg/minutes on 2 different days. The participants were pretreated with sumatriptan tablets (2 × 50 mg) 1 day and with placebo the other day. During the infusion, the participants were asked about side effects including a detailed description about their GI symptoms. Clinical observations like flatulence, rumbling, and use of bedpan were also noted. After the infusion, the participants filled out a questionnaire about side effects at home until 12-hour after the infusion start. The study was conducted at the Danish Headache Center at Rigshospitalet Glostrup in the period February 2018 to July 2018. Results: On both study days 93% (27/29 participants) experienced symptoms from the GI system during the infusion. Rumbling, stomach pain, nausea, diarrhea, and an urge to defecate were the most commonly experienced GI side effects. There was no difference in symptoms between placebo and sumatriptan pretreatment. Conclusion: We conclude that a 2-hour infusion of CGRP causes frequent and sometimes severe symptoms from the GI system. The symptoms are not antagonized by sumatriptan. More attention should be paid to constipation as a possible side effect of CGRP receptor antagonists.
AB - Objective: The monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are new antimigraine drugs from which many patients already benefit. Very few side effects have been reported from the antibody trials, including very few gastrointestinal (GI) side effects. The current data derive from a double-blind cross-over study of CGRP infusion for 2 hours. We present the GI side effects of the infusion and raise the question if underreporting of GI symptoms in CGRP antibody trials has occurred. We also discuss why constipation may be more likely with CGRP receptor blockade than with CGRP neutralizing antibodies. Methods: Thirty healthy volunteers were recruited to receive a 2-hour infusion of CGRP 1.5 µg/minutes on 2 different days. The participants were pretreated with sumatriptan tablets (2 × 50 mg) 1 day and with placebo the other day. During the infusion, the participants were asked about side effects including a detailed description about their GI symptoms. Clinical observations like flatulence, rumbling, and use of bedpan were also noted. After the infusion, the participants filled out a questionnaire about side effects at home until 12-hour after the infusion start. The study was conducted at the Danish Headache Center at Rigshospitalet Glostrup in the period February 2018 to July 2018. Results: On both study days 93% (27/29 participants) experienced symptoms from the GI system during the infusion. Rumbling, stomach pain, nausea, diarrhea, and an urge to defecate were the most commonly experienced GI side effects. There was no difference in symptoms between placebo and sumatriptan pretreatment. Conclusion: We conclude that a 2-hour infusion of CGRP causes frequent and sometimes severe symptoms from the GI system. The symptoms are not antagonized by sumatriptan. More attention should be paid to constipation as a possible side effect of CGRP receptor antagonists.
KW - calcitonin gene-related peptide
KW - calcitonin gene-related peptide antibodies
KW - erenumab
KW - gastrointestinal
KW - migraine
U2 - 10.1111/head.13795
DO - 10.1111/head.13795
M3 - Journal article
C2 - 32227602
AN - SCOPUS:85082959227
VL - 60
SP - 929
EP - 937
JO - Headache
JF - Headache
SN - 0017-8748
IS - 5
ER -
ID: 254463855