Case

Ms. M, age 38, presents with frequent unilateral headaches. She experiences blurriness in her right visual field for 20 to 30 minutes before the onset of pain. These events have been present intermittently for the past 2 years, during which she had 5 to 7 attacks per month. Over the past 4 months, she has had attacks on 18 to 20 days per month with no findings on her neurologic exam.

In the past, Ms. M’s headache attacks have been treated with 60 mg of propranolol and 40 mg of nortriptyline as prophylactic medications. She discontinued use because of a lack of efficacy and the inability to tolerate the side effects, such as dizziness and fatigue. She has used zolmitriptan for headache rescue but stopped this medication because of uncomfortable chest tightness and nausea. Since then, Ms. M has taken acetaminophen/aspirin/caffeine and ibuprofen as needed but has noted minimal pain relief.

Ms. M recently initiated galcanezumab as a prophylactic therapy and has since had a significant decrease in headache days per month. She has also noted the severity of her attacks has decreased and in the 4 months after she began galcanezumab she has only needed to take ibuprofen for headache 8 times. She has not needed to take her new rescue medicine, eletriptan hydrobromide, since beginning galcanezumab because her attacks have been of lesser severity. Ms. M has noted a dramatic improvement in her quality of life and ability to partake in her daily activities.

Challenge Questions

1. Based on the information presented, which diagnosis is most appropriate?

a. Cluster headache

b. Tension headache

c. Migraine with aura

d. Migraine without aura

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C, Based on the information presented, migraine with aura is the most appropriate diagnosis

2. What are the clinical indications to use calcitonin gene-related peptide (CGRP) inhibitors as a potential therapy?

a. Chronic migraine and episodic migraine

b. Tension-type headache and trigeminal neuralgia

c. Chronic migraine, episodic migraine, and tension type headache

d. Chronic migraine, episodic migraine, and trigeminal neuralgia

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A, Chronic migraine and episodic migraine are the clinical indications to use calcitonin gene-related peptide (CGRP) inhibitors as a potential therapy

3. What is the mechanism of action of CGRP inhibitors?

a. CGRP inhibitors block the neurogenic cascade that leads to vasodilation and the pain associated with migraine attacks

b. CGRP inhibitors prevent the release of acetylcholine at the neuromuscular junction, which reduces tension in the muscles of the head to prevent migraines

c. CGRP inhibitors are 5HT serotonin agonists, which promote vasoconstriction

d. CGRP inhibitors are a cytochrome P450 3A4 inducer to decrease CNS activity

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A, The CGRP inhibitors block the neurogenic cascade that leads to the vasodilation and pain associated with migraine attacks

4. What is the recommended dosing schedule?

a. Daily pill

b. Weekly injection

c. Monthly infusion

d. Monthly injection

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D, Monthly injection is the recommended dosing schedule for CGRP inhibitors

5. What was the primary clinical trial endpoint in the study leading to Food and Drug Administration (FDA) approval of erenumab?

a. Tolerability of erenumab as compared with previous prophylactic medications

b. Proportion of participants with a 50% reduction in migraine days, per their individual baseline, during the third month of the double-blind trial

c. Proportion of participants with a 25% reduction in migraine days, compared with the placebo group, during the third month of the double-blind trial

d. Proportion of participants with a 75% reduction in migraine days, compared with the placebo group, during the third month of the double-blind trial

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B, The proportion of participants with a 50% reduction in migraine days, per their individual baseline, during the third month of the double-blind trial was the primary clinical trial endpoint in the study leading to FDA approval of erenumab

6. What were the secondary endpoints that lead to the FDA approval of galcanezumab?

a. Mean percentage of participants reaching at least 40% reduction from baseline number of monthly migraine days after 4 months of treatment, and mean change of impact of migraine on activities of daily living compared with baseline

b. Mean change in use of acute headache medication during the treatment period

c. Mean percentage of participants reaching at least 50%, 75%, and 100% reduction from baseline number of monthly migraine days after 3 months of treatment; mean change in use of acute migraine treatments; and mean change in effect of migraine on activities of daily living

d. Mean percentage of participants reaching at least 40%, 50%, 75%, and 100% reduction in monthly migraine days over 4 months, mean change in use of acute migraine treatment, and mean change in effect of migraine on activities of daily living

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C, Mean percentage of participants reaching at least 50%, 75%, and 100% reduction from baseline number of monthly migraine days after 3 months of treatment; mean change in use of acute migraine treatments; and mean change in effect of migraine on activities of daily living were the secondary endpoints that lead to the FDA approval of galcanezumab

7. Which side effects have been reported with the use of all of the CGRP-inhibitors?

a. Nausea, vomiting, and fever

b. Injection-site reaction and constipation

c. Constipation

d. Drowsiness, vomiting, and irritability

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C, Side effects of all of the CGRP inhibitors are injection-site reaction and constipation

1. Dodick DW. Migraine. Lancet. 2018;391(10127):1315-1330.

2. Schuster NM, Rapoport AM. Calcitonin gene-related peptide-targeted therapies for migraine and cluster headache: a review. Clinical Neuropharmacol. 2017;40(4):169-174.

3. Bigal ME, Dodick DW, Rapoport AM, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicenter, randomized, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14(11):1081-1090.

4. Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(5):382-390.

5. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425-34.

6. Uwe R, Goadsby PJ, Lanteri-Minet, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom 2 to 4 previous preventative treatments were unsuccessful: a randomized, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280-2287.

KSC is a member of the speaker bureau and a consultant for Eli Lilly and Company.