Migraine ICYMI

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563

Key clinical point: Meta-analysis on 10 years of real-world data confirmed the efficacy of onabotulinumtoxinA as a preventive treatment for chronic migraine.

Major finding: At week 24, onabotulinumtoxinA reduced the number of headache days per month (mean change from baseline [MCFB] −10.64; 95% CI −12.31 to −8.97), with a ≥50% reduction in migraine days response rate of 46.57% (95% CI 29.50%-63.65%) and improvements in total Headache Impact Test-6 score (MCFB −11.70; 95% CI −13.86 to −9.54) and Migraine-Specific Quality of Life v2.1 score (MCFB 23.60; 95% CI 21.56-25.64). The improvements were maintained till 52 weeks.

Study details: Findings are from a systematic review and meta-analysis of 44 studies including patients with chronic migraine who received onabotulinumtoxinA.

Disclosures: This study was supported by AbbVie. M Lanteri-Minet reported receiving personal fees and grants from various sources. Four authors declared being employees of AbbVie or working for a consultancy company commissioned by AbbVie or holding stock options in GSK and AbbVie.

Source: Lanteri-Minet M et al. Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Cephalalgia. 2022 (Sep 8). Doi: 10.1177/03331024221123058

Key clinical point: Meta-analysis on 10 years of real-world data confirmed the efficacy of onabotulinumtoxinA as a preventive treatment for chronic migraine.

Major finding: At week 24, onabotulinumtoxinA reduced the number of headache days per month (mean change from baseline [MCFB] −10.64; 95% CI −12.31 to −8.97), with a ≥50% reduction in migraine days response rate of 46.57% (95% CI 29.50%-63.65%) and improvements in total Headache Impact Test-6 score (MCFB −11.70; 95% CI −13.86 to −9.54) and Migraine-Specific Quality of Life v2.1 score (MCFB 23.60; 95% CI 21.56-25.64). The improvements were maintained till 52 weeks.

Study details: Findings are from a systematic review and meta-analysis of 44 studies including patients with chronic migraine who received onabotulinumtoxinA.

Disclosures: This study was supported by AbbVie. M Lanteri-Minet reported receiving personal fees and grants from various sources. Four authors declared being employees of AbbVie or working for a consultancy company commissioned by AbbVie or holding stock options in GSK and AbbVie.

Source: Lanteri-Minet M et al. Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Cephalalgia. 2022 (Sep 8). Doi: 10.1177/03331024221123058

Key clinical point: Meta-analysis on 10 years of real-world data confirmed the efficacy of onabotulinumtoxinA as a preventive treatment for chronic migraine.

Major finding: At week 24, onabotulinumtoxinA reduced the number of headache days per month (mean change from baseline [MCFB] −10.64; 95% CI −12.31 to −8.97), with a ≥50% reduction in migraine days response rate of 46.57% (95% CI 29.50%-63.65%) and improvements in total Headache Impact Test-6 score (MCFB −11.70; 95% CI −13.86 to −9.54) and Migraine-Specific Quality of Life v2.1 score (MCFB 23.60; 95% CI 21.56-25.64). The improvements were maintained till 52 weeks.

Study details: Findings are from a systematic review and meta-analysis of 44 studies including patients with chronic migraine who received onabotulinumtoxinA.

Disclosures: This study was supported by AbbVie. M Lanteri-Minet reported receiving personal fees and grants from various sources. Four authors declared being employees of AbbVie or working for a consultancy company commissioned by AbbVie or holding stock options in GSK and AbbVie.

Source: Lanteri-Minet M et al. Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Cephalalgia. 2022 (Sep 8). Doi: 10.1177/03331024221123058

Key clinical point: Patients with migraine treated with anti-calcitonin gene-related peptide (anti-CGRP) receptor monoclonal antibodies (mAb), erenumab and fremanezumab, reported an increase in systolic and diastolic blood pressure, with most having blood pressure within normal limits but some requiring antihypertensive treatment.

Major finding: At 3 months, patients treated with erenumab or fremanezumab reported a significant increase in systolic (change from baseline [Δ] 5.0 mm Hg; P < .001) and diastolic (Δ 3.3 mm Hg; P < .001) blood pressure, with sustained effects over 1 year of follow-up (P < .001). Antihypertensive treatment was required by 3.7% of patients treated with erenumab.

Study details: This prospective follow-up study included 196 patients with migraine who previously failed ≥4 migraine preventive treatments and received erenumab or fremanezumab and 109 patients with migraine who did not use any migraine prophylactic medication.

Disclosures: This study did not receive any targeted funding. AM van den Brink and GM Terwindt reported receiving independent, consultancy, or industry support from various sources.

Source: de Vries Lentsch S et al. Blood pressure in migraine patients treated with monoclonal anti-CGRP (receptor) antibodies: A prospective follow-up study. Neurology. 2022 (Oct 4). Doi: 10.1212/WNL.0000000000201008

Key clinical point: Patients with migraine treated with anti-calcitonin gene-related peptide (anti-CGRP) receptor monoclonal antibodies (mAb), erenumab and fremanezumab, reported an increase in systolic and diastolic blood pressure, with most having blood pressure within normal limits but some requiring antihypertensive treatment.

Major finding: At 3 months, patients treated with erenumab or fremanezumab reported a significant increase in systolic (change from baseline [Δ] 5.0 mm Hg; P < .001) and diastolic (Δ 3.3 mm Hg; P < .001) blood pressure, with sustained effects over 1 year of follow-up (P < .001). Antihypertensive treatment was required by 3.7% of patients treated with erenumab.

Study details: This prospective follow-up study included 196 patients with migraine who previously failed ≥4 migraine preventive treatments and received erenumab or fremanezumab and 109 patients with migraine who did not use any migraine prophylactic medication.

Disclosures: This study did not receive any targeted funding. AM van den Brink and GM Terwindt reported receiving independent, consultancy, or industry support from various sources.

Source: de Vries Lentsch S et al. Blood pressure in migraine patients treated with monoclonal anti-CGRP (receptor) antibodies: A prospective follow-up study. Neurology. 2022 (Oct 4). Doi: 10.1212/WNL.0000000000201008

Key clinical point: Patients with migraine treated with anti-calcitonin gene-related peptide (anti-CGRP) receptor monoclonal antibodies (mAb), erenumab and fremanezumab, reported an increase in systolic and diastolic blood pressure, with most having blood pressure within normal limits but some requiring antihypertensive treatment.

Major finding: At 3 months, patients treated with erenumab or fremanezumab reported a significant increase in systolic (change from baseline [Δ] 5.0 mm Hg; P < .001) and diastolic (Δ 3.3 mm Hg; P < .001) blood pressure, with sustained effects over 1 year of follow-up (P < .001). Antihypertensive treatment was required by 3.7% of patients treated with erenumab.

Study details: This prospective follow-up study included 196 patients with migraine who previously failed ≥4 migraine preventive treatments and received erenumab or fremanezumab and 109 patients with migraine who did not use any migraine prophylactic medication.

Disclosures: This study did not receive any targeted funding. AM van den Brink and GM Terwindt reported receiving independent, consultancy, or industry support from various sources.

Source: de Vries Lentsch S et al. Blood pressure in migraine patients treated with monoclonal anti-CGRP (receptor) antibodies: A prospective follow-up study. Neurology. 2022 (Oct 4). Doi: 10.1212/WNL.0000000000201008

Headache as a symptom of COVID-19 could help predict survival for inpatients with the disease, according to recent research published in the journal Headache.

In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.

Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.

Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.

The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.

“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
 

More data needed on association between headache and COVID-19

While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”

The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”

In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”

Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.

“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”

One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”

Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.

Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.

Headache as a symptom of COVID-19 could help predict survival for inpatients with the disease, according to recent research published in the journal Headache.

In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.

Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.

Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.

The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.

“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
 

More data needed on association between headache and COVID-19

While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”

The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”

In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”

Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.

“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”

One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”

Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.

Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.

Headache as a symptom of COVID-19 could help predict survival for inpatients with the disease, according to recent research published in the journal Headache.

In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.

Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.

Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.

The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.

“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
 

More data needed on association between headache and COVID-19

While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”

The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”

In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”

Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.

“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”

One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”

Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.

Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

Key clinical point: This real-world analysis confirms the benefits of anticalcitonin gene-related peptide (anti-CGRP) drugs, erenumab, galcanezumab, and fremanezumab, in drug-resistant chronic migraine; however, intensified erenumab regimen showed limited benefits.

Major finding: At week 12, all patients treated with erenumab (P < .001), galcanezumab (P < .001), or fremanezumab (P = .028) achieved a significant reduction in mean monthly migraine headache days, with treatment-associated toxicity being higher with erenumab vs galcanezumab and fremanezumab (P  =  .04). An intensified erenumab regimen demonstrated similar efficacy but with more severe grade 3/4 toxicity (140 vs 70 mg: 14.8% vs 0%; P  =  .038).

Study details: This was a retrospective study including 104 patients with drug-resistant chronic migraine who had failed >3 conventional migraine preventive treatments and received erenumab, galcanezumab, or fremanezumab.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest.

Source: Cantarelli L et al. Efficacy and safety of erenumab, galcanezumab, and fremanezumab in the treatment of drug-resistant chronic migraine: Experience in real clinical practice. Ann Pharmacother. 2022 (Aug 18). Doi: 10.1177/10600280221118402

Key clinical point: This real-world analysis confirms the benefits of anticalcitonin gene-related peptide (anti-CGRP) drugs, erenumab, galcanezumab, and fremanezumab, in drug-resistant chronic migraine; however, intensified erenumab regimen showed limited benefits.

Major finding: At week 12, all patients treated with erenumab (P < .001), galcanezumab (P < .001), or fremanezumab (P = .028) achieved a significant reduction in mean monthly migraine headache days, with treatment-associated toxicity being higher with erenumab vs galcanezumab and fremanezumab (P  =  .04). An intensified erenumab regimen demonstrated similar efficacy but with more severe grade 3/4 toxicity (140 vs 70 mg: 14.8% vs 0%; P  =  .038).

Study details: This was a retrospective study including 104 patients with drug-resistant chronic migraine who had failed >3 conventional migraine preventive treatments and received erenumab, galcanezumab, or fremanezumab.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest.

Source: Cantarelli L et al. Efficacy and safety of erenumab, galcanezumab, and fremanezumab in the treatment of drug-resistant chronic migraine: Experience in real clinical practice. Ann Pharmacother. 2022 (Aug 18). Doi: 10.1177/10600280221118402

Key clinical point: This real-world analysis confirms the benefits of anticalcitonin gene-related peptide (anti-CGRP) drugs, erenumab, galcanezumab, and fremanezumab, in drug-resistant chronic migraine; however, intensified erenumab regimen showed limited benefits.

Major finding: At week 12, all patients treated with erenumab (P < .001), galcanezumab (P < .001), or fremanezumab (P = .028) achieved a significant reduction in mean monthly migraine headache days, with treatment-associated toxicity being higher with erenumab vs galcanezumab and fremanezumab (P  =  .04). An intensified erenumab regimen demonstrated similar efficacy but with more severe grade 3/4 toxicity (140 vs 70 mg: 14.8% vs 0%; P  =  .038).

Study details: This was a retrospective study including 104 patients with drug-resistant chronic migraine who had failed >3 conventional migraine preventive treatments and received erenumab, galcanezumab, or fremanezumab.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest.

Source: Cantarelli L et al. Efficacy and safety of erenumab, galcanezumab, and fremanezumab in the treatment of drug-resistant chronic migraine: Experience in real clinical practice. Ann Pharmacother. 2022 (Aug 18). Doi: 10.1177/10600280221118402