PMC:7507645 / 30023-31837 JSONTXT

{"project":"TEST0","denotations":[{"id":"32958075-153-159-1506692","span":{"begin":1390,"end":1392},"obj":"[\"24117004\"]"},{"id":"32958075-157-163-1506693","span":{"begin":1394,"end":1396},"obj":"[\"31174999\"]"},{"id":"32958075-179-185-1506694","span":{"begin":1649,"end":1651},"obj":"[\"27206958\"]"}],"text":"These findings have certain limitations. These subgroup analyses were not prespecified in the HALO CM protocol; however, the measures evaluated were generally consistent with the observed effects in the FAS population, and all data points in these subgroups were collected a priori. In addition, this study did not consider the intensity of MO, differentiate between the types or combination of medications taken, nor did it consider the presence and severity of comborbid psychiatric disorders that may contribute to MO, such as anxiety or cephalophobia. Future studies to determine whether the type of overused medication impacts outcomes would be beneficial. Due to exclusion criteria, patients using opioids or barbiturates on more than 4 days per month were not included in this trial; therefore, inferences cannot be drawn about patients overusing these drugs. Furthermore, one cannot rule out that the routine observation by doctors over the course of the trial may have contributed to some of the observed reductions in MO; however, placebo-treated patients were observed in a similar manner with smaller improvements. The current understanding of the pathophysiology of MO also supports the role of fremanezumab in reducing MO. Increased CGRP expression and release is hypothesized to play a role in the development of the increased sensitivity to pain perception that MO fosters [29, 30]. This sensitization may be reversed by blocking CGRP with fremanezumab. In triptan- or morphine-sensitized rats, a single administration of fremanezumab was able to prevent cutaneous allodynia resulting from triggers associated with migraine attacks [31]. Lastly, headache data were captured using a patient self-reported diary, which can vary in terms of content recorded, reading and writing skill, and compliance."}

{"project":"2_test","denotations":[{"id":"32958075-24117004-60560899","span":{"begin":1390,"end":1392},"obj":"24117004"},{"id":"32958075-31174999-60560900","span":{"begin":1394,"end":1396},"obj":"31174999"},{"id":"32958075-27206958-60560901","span":{"begin":1649,"end":1651},"obj":"27206958"}],"text":"These findings have certain limitations. These subgroup analyses were not prespecified in the HALO CM protocol; however, the measures evaluated were generally consistent with the observed effects in the FAS population, and all data points in these subgroups were collected a priori. In addition, this study did not consider the intensity of MO, differentiate between the types or combination of medications taken, nor did it consider the presence and severity of comborbid psychiatric disorders that may contribute to MO, such as anxiety or cephalophobia. Future studies to determine whether the type of overused medication impacts outcomes would be beneficial. Due to exclusion criteria, patients using opioids or barbiturates on more than 4 days per month were not included in this trial; therefore, inferences cannot be drawn about patients overusing these drugs. Furthermore, one cannot rule out that the routine observation by doctors over the course of the trial may have contributed to some of the observed reductions in MO; however, placebo-treated patients were observed in a similar manner with smaller improvements. The current understanding of the pathophysiology of MO also supports the role of fremanezumab in reducing MO. Increased CGRP expression and release is hypothesized to play a role in the development of the increased sensitivity to pain perception that MO fosters [29, 30]. This sensitization may be reversed by blocking CGRP with fremanezumab. In triptan- or morphine-sensitized rats, a single administration of fremanezumab was able to prevent cutaneous allodynia resulting from triggers associated with migraine attacks [31]. Lastly, headache data were captured using a patient self-reported diary, which can vary in terms of content recorded, reading and writing skill, and compliance."}