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Adding CGRP to Botox is safe and effective for migraine prevention
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
FROM AHS 2020
NSAID/triptan combination improves treatment-resistant migraine
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
FROM AHS 2020
CGRPs in real world: Similar efficacy, more AEs
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
FROM AHS 2020
Intranasal DHE shows promise in migraine
, according to results from a phase 3 clinical trial. In development by Impel NeuroPharma, the new formulation could offer patients an at-home alternative to intramuscular infusions or intravenous injections currently used to deliver DHE.
“Our analysis of the data suggests that nothing new or untoward seemed to be happening as a result of delivering DHE to the upper nasal space,” Stephen Shrewsbury, MD, chief medical officer of Impel NeuroPharma, said in an interview. The company released key results from its phase 3 clinical trial, while a poster examining patient satisfaction was presented by Dr. Shrewsbury at the virtual annual meeting of the American Headache Society.
An improved intranasal formulation
The product isn’t the first effort to develop an inhaled form of DHE. An inhaled version called Migranal, marketed by Bausch Health, delivers DHE to the front part of the nose, where it may be lost to the upper lip or down the throat, according to Dr. Shrewsbury. Impel’s formulation (INP104) delivers the drug to the upper nasal space, where an earlier phase 1 trial demonstrated it could achieve higher serum concentrations compared with Migranal.
In 2018, MAP Pharmaceuticals came close to a product, but it was ultimately rejected by the Food and Drug Administration because DHE was not stable in the propellant used in the formulation. This time is different, said Dr. Shrewsbury, who was chief medical officer at MAP before joining Impel. The new device holds DHE and the propellant in separate compartments until they are combined right before use, which should circumvent stability problems.
Dr. Shrewsbury believes that patients will welcome an inhaled version of DHE. “People with migraines don’t want to have to go into hospital or even an infusion center if they can help it,” he said.
The study was one of a number of presentations at the AHS meeting that focused on novel delivery methods for established drugs. “The idea of taking things that we know work and improving upon them, both in terms of formulation and then delivery, that’s a common theme. My impression is that this will be an interesting arrow to have in our sling,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, who was not involved in the study.
Open-label trial results
The STOP 301 phase 3 open-label safety and tolerability trial treated over 5,650 migraine attacks in 354 patients who self-administered INP104 for up to 52 weeks. They were provided up to three doses per week (1.45 mg in a dose of two puffs, one per nostril). Maximum doses included two per day and three per week.
There were no new safety signals or concern trends in nasal safety findings. 15.0% of patients experienced nasal congestion, 6.8% nausea, 5.1% nasal discomfort, and 5.1% unpleasant taste.
A total of 66.3% of participants reported pain relief by 2 hours (severe or moderate pain reduced to mild or none, or mild pain reduced to none) following a dose, and 38% had freedom from pain. 16.3% reported pain relief onset at 15 minutes, with continued improvement over time. During weeks 21-24 of the study, 98.4% and 95% of patients reporting no recurrence of their migraine or use of rescue medications during the 24- and 48-hour periods after using INP104. “Once they got rid of the pain, it didn’t come back, and that’s been one of the shortcomings of many of the available oral therapies – although some of them can be quite effective, that effect can wear off and people can find their migraine comes back within a 24- or 48-hour period,” said Dr. Shrewsbury.
The drug was also rated as convenient, with 83.6% of participants strongly agreeing (50%) or agreeing (33.6%) that it is easy to use.
“It certainly looks like compliance will be good. The possibility is that this will be quite useful,” said Dr. Charles, who is also enthusiastic about some of the other drug formulations announced at the meeting. “It really is just fun times for us as clinicians to be able to have so many different options for patients,” he said.
Dr. Shrewsbury is an employee of Impel NeuroPharma, which funded the study.* Dr. Charles consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Shrewsbury S, et al. AHS 2020. Abstract 832509.
*Correction, 6/19/20: An earlier version of this article misstated the name of Impel NeuroPharma.
, according to results from a phase 3 clinical trial. In development by Impel NeuroPharma, the new formulation could offer patients an at-home alternative to intramuscular infusions or intravenous injections currently used to deliver DHE.
“Our analysis of the data suggests that nothing new or untoward seemed to be happening as a result of delivering DHE to the upper nasal space,” Stephen Shrewsbury, MD, chief medical officer of Impel NeuroPharma, said in an interview. The company released key results from its phase 3 clinical trial, while a poster examining patient satisfaction was presented by Dr. Shrewsbury at the virtual annual meeting of the American Headache Society.
An improved intranasal formulation
The product isn’t the first effort to develop an inhaled form of DHE. An inhaled version called Migranal, marketed by Bausch Health, delivers DHE to the front part of the nose, where it may be lost to the upper lip or down the throat, according to Dr. Shrewsbury. Impel’s formulation (INP104) delivers the drug to the upper nasal space, where an earlier phase 1 trial demonstrated it could achieve higher serum concentrations compared with Migranal.
In 2018, MAP Pharmaceuticals came close to a product, but it was ultimately rejected by the Food and Drug Administration because DHE was not stable in the propellant used in the formulation. This time is different, said Dr. Shrewsbury, who was chief medical officer at MAP before joining Impel. The new device holds DHE and the propellant in separate compartments until they are combined right before use, which should circumvent stability problems.
Dr. Shrewsbury believes that patients will welcome an inhaled version of DHE. “People with migraines don’t want to have to go into hospital or even an infusion center if they can help it,” he said.
The study was one of a number of presentations at the AHS meeting that focused on novel delivery methods for established drugs. “The idea of taking things that we know work and improving upon them, both in terms of formulation and then delivery, that’s a common theme. My impression is that this will be an interesting arrow to have in our sling,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, who was not involved in the study.
Open-label trial results
The STOP 301 phase 3 open-label safety and tolerability trial treated over 5,650 migraine attacks in 354 patients who self-administered INP104 for up to 52 weeks. They were provided up to three doses per week (1.45 mg in a dose of two puffs, one per nostril). Maximum doses included two per day and three per week.
There were no new safety signals or concern trends in nasal safety findings. 15.0% of patients experienced nasal congestion, 6.8% nausea, 5.1% nasal discomfort, and 5.1% unpleasant taste.
A total of 66.3% of participants reported pain relief by 2 hours (severe or moderate pain reduced to mild or none, or mild pain reduced to none) following a dose, and 38% had freedom from pain. 16.3% reported pain relief onset at 15 minutes, with continued improvement over time. During weeks 21-24 of the study, 98.4% and 95% of patients reporting no recurrence of their migraine or use of rescue medications during the 24- and 48-hour periods after using INP104. “Once they got rid of the pain, it didn’t come back, and that’s been one of the shortcomings of many of the available oral therapies – although some of them can be quite effective, that effect can wear off and people can find their migraine comes back within a 24- or 48-hour period,” said Dr. Shrewsbury.
The drug was also rated as convenient, with 83.6% of participants strongly agreeing (50%) or agreeing (33.6%) that it is easy to use.
“It certainly looks like compliance will be good. The possibility is that this will be quite useful,” said Dr. Charles, who is also enthusiastic about some of the other drug formulations announced at the meeting. “It really is just fun times for us as clinicians to be able to have so many different options for patients,” he said.
Dr. Shrewsbury is an employee of Impel NeuroPharma, which funded the study.* Dr. Charles consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Shrewsbury S, et al. AHS 2020. Abstract 832509.
*Correction, 6/19/20: An earlier version of this article misstated the name of Impel NeuroPharma.
, according to results from a phase 3 clinical trial. In development by Impel NeuroPharma, the new formulation could offer patients an at-home alternative to intramuscular infusions or intravenous injections currently used to deliver DHE.
“Our analysis of the data suggests that nothing new or untoward seemed to be happening as a result of delivering DHE to the upper nasal space,” Stephen Shrewsbury, MD, chief medical officer of Impel NeuroPharma, said in an interview. The company released key results from its phase 3 clinical trial, while a poster examining patient satisfaction was presented by Dr. Shrewsbury at the virtual annual meeting of the American Headache Society.
An improved intranasal formulation
The product isn’t the first effort to develop an inhaled form of DHE. An inhaled version called Migranal, marketed by Bausch Health, delivers DHE to the front part of the nose, where it may be lost to the upper lip or down the throat, according to Dr. Shrewsbury. Impel’s formulation (INP104) delivers the drug to the upper nasal space, where an earlier phase 1 trial demonstrated it could achieve higher serum concentrations compared with Migranal.
In 2018, MAP Pharmaceuticals came close to a product, but it was ultimately rejected by the Food and Drug Administration because DHE was not stable in the propellant used in the formulation. This time is different, said Dr. Shrewsbury, who was chief medical officer at MAP before joining Impel. The new device holds DHE and the propellant in separate compartments until they are combined right before use, which should circumvent stability problems.
Dr. Shrewsbury believes that patients will welcome an inhaled version of DHE. “People with migraines don’t want to have to go into hospital or even an infusion center if they can help it,” he said.
The study was one of a number of presentations at the AHS meeting that focused on novel delivery methods for established drugs. “The idea of taking things that we know work and improving upon them, both in terms of formulation and then delivery, that’s a common theme. My impression is that this will be an interesting arrow to have in our sling,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, who was not involved in the study.
Open-label trial results
The STOP 301 phase 3 open-label safety and tolerability trial treated over 5,650 migraine attacks in 354 patients who self-administered INP104 for up to 52 weeks. They were provided up to three doses per week (1.45 mg in a dose of two puffs, one per nostril). Maximum doses included two per day and three per week.
There were no new safety signals or concern trends in nasal safety findings. 15.0% of patients experienced nasal congestion, 6.8% nausea, 5.1% nasal discomfort, and 5.1% unpleasant taste.
A total of 66.3% of participants reported pain relief by 2 hours (severe or moderate pain reduced to mild or none, or mild pain reduced to none) following a dose, and 38% had freedom from pain. 16.3% reported pain relief onset at 15 minutes, with continued improvement over time. During weeks 21-24 of the study, 98.4% and 95% of patients reporting no recurrence of their migraine or use of rescue medications during the 24- and 48-hour periods after using INP104. “Once they got rid of the pain, it didn’t come back, and that’s been one of the shortcomings of many of the available oral therapies – although some of them can be quite effective, that effect can wear off and people can find their migraine comes back within a 24- or 48-hour period,” said Dr. Shrewsbury.
The drug was also rated as convenient, with 83.6% of participants strongly agreeing (50%) or agreeing (33.6%) that it is easy to use.
“It certainly looks like compliance will be good. The possibility is that this will be quite useful,” said Dr. Charles, who is also enthusiastic about some of the other drug formulations announced at the meeting. “It really is just fun times for us as clinicians to be able to have so many different options for patients,” he said.
Dr. Shrewsbury is an employee of Impel NeuroPharma, which funded the study.* Dr. Charles consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Shrewsbury S, et al. AHS 2020. Abstract 832509.
*Correction, 6/19/20: An earlier version of this article misstated the name of Impel NeuroPharma.
FROM AHS 2020
Persistent posttraumatic headache risk factors confirmed
It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.
“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.
He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.
Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.
“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
Defining risk factors
The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.
A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
Identifying patient subgroups
The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”
Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.
The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.
“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.
He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.
Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.
“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
Defining risk factors
The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.
A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
Identifying patient subgroups
The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”
Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.
The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.
“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.
He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.
Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.
“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
Defining risk factors
The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.
A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
Identifying patient subgroups
The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”
Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.
The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.
FROM AHS 2020
Few patients with migraine clear barriers to optimal care
, new research shows.
Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.
The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.
“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.
The study was presented at the virtual annual meeting of the American Headache Society.
Ongoing challenges
Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.
Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.
The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.
Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.
In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.
A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.
Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.
Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.
Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.
“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.
Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.
The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.
“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.
“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.
The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.
This article first appeared on Medscape.com.
, new research shows.
Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.
The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.
“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.
The study was presented at the virtual annual meeting of the American Headache Society.
Ongoing challenges
Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.
Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.
The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.
Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.
In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.
A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.
Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.
Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.
Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.
“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.
Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.
The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.
“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.
“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.
The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.
This article first appeared on Medscape.com.
, new research shows.
Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.
The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.
“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.
The study was presented at the virtual annual meeting of the American Headache Society.
Ongoing challenges
Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.
Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.
The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.
Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.
In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.
A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.
Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.
Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.
Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.
“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.
Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.
The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.
“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.
“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.
The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.
This article first appeared on Medscape.com.
From AHS 2020
Population study supports migraine–dementia link
Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.
“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
A national register-based study
The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.
A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.
“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.
The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.
“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”
The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.
“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”
Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.
One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.
Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.
“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
‘Surprising’ findings
Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”
He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.
“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”
Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
SOURCE: Islamoska S et al. AHS 2020, Submission 846214.
Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.
“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
A national register-based study
The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.
A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.
“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.
The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.
“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”
The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.
“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”
Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.
One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.
Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.
“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
‘Surprising’ findings
Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”
He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.
“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”
Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
SOURCE: Islamoska S et al. AHS 2020, Submission 846214.
Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.
“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
A national register-based study
The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.
A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.
“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.
The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.
“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”
The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.
“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”
Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.
One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.
Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.
“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
‘Surprising’ findings
Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”
He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.
“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”
Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
SOURCE: Islamoska S et al. AHS 2020, Submission 846214.
FROM AHS 2020
Cannabis misconceptions still common among MS clinicians
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
From CMSC 2020
I’m getting old (and it’s costing me)
The inevitable consequences of aging finally hit me last year, at age 64. Before then, I was a (reasonably) healthy, active person. I exercised a little, ate reasonably healthy meals, and took no medications. My only visits to my doctor were for annual (sort of) exams. That all changed when I began to have neurogenic claudication in both legs. I had no history of back injury but, with worsening pain, I sought the opinion of my physician.
It turned out that I had a dynamic spondylolisthesis and disc herniation that could only be fixed with a single-level fusion. From a neurologic perspective, the procedure was an unequivocal success. However, my recovery (with lack of exercise) had the unintended “side effect” of a 25-pound weight gain. As a family doctor, I know that the best way to reverse this gain is by increasing my exercise. However, I also know that, at my age, many specialty organizations recommend a cardiac evaluation before beginning strenuous exercise.1
So, I set up a routine treadmill test. Although I exercised to a moderate level of intensity, the interpreting cardiologist was unwilling to call my test “totally normal” and recommended further evaluation. (One of the “unwritten rules” I’ve discovered during my career is that adverse outcomes are far more likely in medical personnel than in nonmedical personnel!)
He recommended undergoing coronary artery computed tomography angiography with coronary artery calcium (CAC) scoring. The result? A left anterior descending artery CAC score of 22, which placed me at a slightly increased risk of an adverse event over the next 10 years. (The benefit of exercise, however, far outweighed the risk.) I’m happy to report that I have lost five pounds with only mildly intensive exercise.
Along with facing the health aspects of aging, I am also faced with the economic realities. I have carried group term life insurance throughout my career. My 10-year term just happened to expire when I turned 65. I have always been insured as a “Tier 1” customer, meaning that I qualified for the best premiums due to my “healthy” status. That said, the transition to age 65 carries with it a significant premium increase.
Imagine my shock, though, when I was told that my premium would jump to MORE THAN 4 TIMES the previous premium for ONE-THIRD of my previous coverage! The culprit? The CAC score of 22!
It turns out that the insurance industry has adopted an underwriting standard that uses CAC—measured over a broad population, rather than a more age-confined one—to determine actuarial risk when rating life insurance policies.2 As a result, my underwriting profile went all the way to “Tier 3.”
Continue to: We're used to medical consequences...
We’re used to medical consequences for tests that we order—whether a prostate biopsy for an elevated prostate-specific antigen test result, breast biopsy after abnormal mammogram, or a hemoglobin A1C test after an elevated fasting blood sugar. We can handle discussions with patients about potential diagnostic paths and readily include that information as part of shared decision-making with patients. Unfortunately, many entities are increasingly using medical information to make nonmedical decisions.
Using the CAC score to discuss the risk of adverse coronary events with my patients may be appropriate. In nonmedical settings, however, this data may be incorrectly, unfairly, or dangerously applied to our patients. I’ve begun thinking about these nonmedical applications as part of the shared decision-making process with my patients. It’s making these conversations more complicated, but life and life events for our patients take place far beyond the walls of our exam rooms.
1. Garner KK, Pomeroy W, Arnold JJ. Exercise stress testing: indications and common questions. Am Fam Physician. 2017;96:293-299A.
2. Rose J. It’s possible to get life insurance with a high calcium score. Good Financial Cents 2019. www.goodfinancialcents.com/life-insurance-with-a-high-calcium-score/. Last modified Febuary 20, 2019. Accessed May 27, 2020.
Michigan State University Department of Family Medicine, East Lansing
The author reported no potential conflict of interest relevant to this article.
Michigan State University Department of Family Medicine, East Lansing
The author reported no potential conflict of interest relevant to this article.
Michigan State University Department of Family Medicine, East Lansing
The author reported no potential conflict of interest relevant to this article.
The inevitable consequences of aging finally hit me last year, at age 64. Before then, I was a (reasonably) healthy, active person. I exercised a little, ate reasonably healthy meals, and took no medications. My only visits to my doctor were for annual (sort of) exams. That all changed when I began to have neurogenic claudication in both legs. I had no history of back injury but, with worsening pain, I sought the opinion of my physician.
It turned out that I had a dynamic spondylolisthesis and disc herniation that could only be fixed with a single-level fusion. From a neurologic perspective, the procedure was an unequivocal success. However, my recovery (with lack of exercise) had the unintended “side effect” of a 25-pound weight gain. As a family doctor, I know that the best way to reverse this gain is by increasing my exercise. However, I also know that, at my age, many specialty organizations recommend a cardiac evaluation before beginning strenuous exercise.1
So, I set up a routine treadmill test. Although I exercised to a moderate level of intensity, the interpreting cardiologist was unwilling to call my test “totally normal” and recommended further evaluation. (One of the “unwritten rules” I’ve discovered during my career is that adverse outcomes are far more likely in medical personnel than in nonmedical personnel!)
He recommended undergoing coronary artery computed tomography angiography with coronary artery calcium (CAC) scoring. The result? A left anterior descending artery CAC score of 22, which placed me at a slightly increased risk of an adverse event over the next 10 years. (The benefit of exercise, however, far outweighed the risk.) I’m happy to report that I have lost five pounds with only mildly intensive exercise.
Along with facing the health aspects of aging, I am also faced with the economic realities. I have carried group term life insurance throughout my career. My 10-year term just happened to expire when I turned 65. I have always been insured as a “Tier 1” customer, meaning that I qualified for the best premiums due to my “healthy” status. That said, the transition to age 65 carries with it a significant premium increase.
Imagine my shock, though, when I was told that my premium would jump to MORE THAN 4 TIMES the previous premium for ONE-THIRD of my previous coverage! The culprit? The CAC score of 22!
It turns out that the insurance industry has adopted an underwriting standard that uses CAC—measured over a broad population, rather than a more age-confined one—to determine actuarial risk when rating life insurance policies.2 As a result, my underwriting profile went all the way to “Tier 3.”
Continue to: We're used to medical consequences...
We’re used to medical consequences for tests that we order—whether a prostate biopsy for an elevated prostate-specific antigen test result, breast biopsy after abnormal mammogram, or a hemoglobin A1C test after an elevated fasting blood sugar. We can handle discussions with patients about potential diagnostic paths and readily include that information as part of shared decision-making with patients. Unfortunately, many entities are increasingly using medical information to make nonmedical decisions.
Using the CAC score to discuss the risk of adverse coronary events with my patients may be appropriate. In nonmedical settings, however, this data may be incorrectly, unfairly, or dangerously applied to our patients. I’ve begun thinking about these nonmedical applications as part of the shared decision-making process with my patients. It’s making these conversations more complicated, but life and life events for our patients take place far beyond the walls of our exam rooms.
The inevitable consequences of aging finally hit me last year, at age 64. Before then, I was a (reasonably) healthy, active person. I exercised a little, ate reasonably healthy meals, and took no medications. My only visits to my doctor were for annual (sort of) exams. That all changed when I began to have neurogenic claudication in both legs. I had no history of back injury but, with worsening pain, I sought the opinion of my physician.
It turned out that I had a dynamic spondylolisthesis and disc herniation that could only be fixed with a single-level fusion. From a neurologic perspective, the procedure was an unequivocal success. However, my recovery (with lack of exercise) had the unintended “side effect” of a 25-pound weight gain. As a family doctor, I know that the best way to reverse this gain is by increasing my exercise. However, I also know that, at my age, many specialty organizations recommend a cardiac evaluation before beginning strenuous exercise.1
So, I set up a routine treadmill test. Although I exercised to a moderate level of intensity, the interpreting cardiologist was unwilling to call my test “totally normal” and recommended further evaluation. (One of the “unwritten rules” I’ve discovered during my career is that adverse outcomes are far more likely in medical personnel than in nonmedical personnel!)
He recommended undergoing coronary artery computed tomography angiography with coronary artery calcium (CAC) scoring. The result? A left anterior descending artery CAC score of 22, which placed me at a slightly increased risk of an adverse event over the next 10 years. (The benefit of exercise, however, far outweighed the risk.) I’m happy to report that I have lost five pounds with only mildly intensive exercise.
Along with facing the health aspects of aging, I am also faced with the economic realities. I have carried group term life insurance throughout my career. My 10-year term just happened to expire when I turned 65. I have always been insured as a “Tier 1” customer, meaning that I qualified for the best premiums due to my “healthy” status. That said, the transition to age 65 carries with it a significant premium increase.
Imagine my shock, though, when I was told that my premium would jump to MORE THAN 4 TIMES the previous premium for ONE-THIRD of my previous coverage! The culprit? The CAC score of 22!
It turns out that the insurance industry has adopted an underwriting standard that uses CAC—measured over a broad population, rather than a more age-confined one—to determine actuarial risk when rating life insurance policies.2 As a result, my underwriting profile went all the way to “Tier 3.”
Continue to: We're used to medical consequences...
We’re used to medical consequences for tests that we order—whether a prostate biopsy for an elevated prostate-specific antigen test result, breast biopsy after abnormal mammogram, or a hemoglobin A1C test after an elevated fasting blood sugar. We can handle discussions with patients about potential diagnostic paths and readily include that information as part of shared decision-making with patients. Unfortunately, many entities are increasingly using medical information to make nonmedical decisions.
Using the CAC score to discuss the risk of adverse coronary events with my patients may be appropriate. In nonmedical settings, however, this data may be incorrectly, unfairly, or dangerously applied to our patients. I’ve begun thinking about these nonmedical applications as part of the shared decision-making process with my patients. It’s making these conversations more complicated, but life and life events for our patients take place far beyond the walls of our exam rooms.
1. Garner KK, Pomeroy W, Arnold JJ. Exercise stress testing: indications and common questions. Am Fam Physician. 2017;96:293-299A.
2. Rose J. It’s possible to get life insurance with a high calcium score. Good Financial Cents 2019. www.goodfinancialcents.com/life-insurance-with-a-high-calcium-score/. Last modified Febuary 20, 2019. Accessed May 27, 2020.
1. Garner KK, Pomeroy W, Arnold JJ. Exercise stress testing: indications and common questions. Am Fam Physician. 2017;96:293-299A.
2. Rose J. It’s possible to get life insurance with a high calcium score. Good Financial Cents 2019. www.goodfinancialcents.com/life-insurance-with-a-high-calcium-score/. Last modified Febuary 20, 2019. Accessed May 27, 2020.
Huntington’s disease biomarkers appear 24 years before clinical symptoms
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
FROM LANCET NEUROLOGY