A Study of Eptinezumab in Participants With Migraine and Medication Overuse Headache

A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that:

• lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• lasted ≥30 minutes and participant had an aura with headache.
• lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• A day with a headache that was successfully treated with a migraine specific treatment.
• A day with an aura without a headache with medication taken.

A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).

CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis.

MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.

Daily Pain assessment data were collected in the headache electronic diary (eDiary) via the question "What was the worst pain intensity of this headache today?". The pain intensity assessment was collected on a 3-point scale: Mild (score = 1), Moderate (score = 2), and Severe (score = 3). For each day, the Daily Pain assessment score was derived by averaging the worst pain intensity over all headaches of that day. For days on which no headaches took place during the relevant period, the Daily Pain score was given as a score of 0. The average Daily Pain score was calculated using the Daily Pain assessments collected during Weeks 1-2.

Acute migraine medication included those medications classified as opioid, barbiturates, ergotamine, triptan, non-opioid analgesic, and combination of analgesic ingredients.

A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that:

• lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• lasted ≥30 minutes and participant had an aura with headache.
• lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• A day with a headache that was successfully treated with a migraine specific treatment.
• A day with an aura without a headache with medication taken.

A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).

CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis.

MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.

Daily Pain assessment data were collected in the headache eDiary via the question "What was the worst pain intensity of this headache today?". The pain intensity assessment was collected on a 3-point scale: Mild (score = 1), Moderate (score = 2), and Severe (score = 3). For each day, the Daily Pain assessment score was derived by averaging the worst pain intensity over all headaches of that day. For days on which no headaches took place during the relevant period, the Daily Pain score was given as a score of 0. The average Daily Pain score was calculated using the Daily Pain assessments collected during Weeks 13-16, 17-20, and 21-24.

Acute migraine medication included paracetamol, triptans, ergotamine, combination of non-opioid analgesics, individual non-opioid analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). Barbiturates and/or opioid analgesics were allowed when considered medically indicated providing its use does not exceed 4 days per month.

CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis.

MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.

A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that:

• lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• lasted ≥30 minutes and participant had an aura with headache.
• lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• A day with a headache that was successfully treated with a migraine specific treatment.
• A day with an aura without a headache with medication taken.

A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that:

• lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• lasted ≥30 minutes and participant had an aura with headache.
• lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• A day with a headache that was successfully treated with a migraine specific treatment.
• A day with an aura without a headache with medication taken.

A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that:

• lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• lasted ≥30 minutes and participant had an aura with headache.
• lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.
• A day with a headache that was successfully treated with a migraine specific treatment.
• A day with an aura without a headache with medication taken.

A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).

A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).

A migraine that fulfilled the criteria for a migraine, was referred to as a migraine attack.

A non-migraine headache that lasted ≥30 minutes or a migraine headache, was referred to as a headache episode.

The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.

The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.

Participants were asked about their most bothersome symptom associated with their migraines during the Baseline Visit. Participants were asked to rate the improvement in this symptom from baseline on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a high score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. The MBS areas included: nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, and other symptoms.

Participants were asked about their most bothersome symptom associated with their migraines during the Baseline Visit. Participants were asked to rate the improvement in this symptom from baseline on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a high score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. The MBS areas included: nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, and other symptoms.

The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49).

The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49).

The mMIDAS is a self-administered questionnaire that contains 7 questions about the headache a participant had in the previous month. The first 5 questions assess the impact of migraine on 3 domains of daily activity: 2 questions for paid work or schoolwork, 2 questions for household work, and 1 question for family, social and leisure activities. The 2 questions for each of the first two groups assess, respectively, the number of days off due to headache, and the number of days in which the productivity was reduced by half or more. mMIDAS total score was derived from the sum of the answers on the first 5 questions. Total score ranged from 0 (little/no disability) to 20 (severe disability) with higher scores indicating more severe disability.

The mMIDAS is a self-administered questionnaire that contains 7 questions about the headache a participant had in the previous month. The first 5 questions assess the impact of migraine on 3 domains of daily activity: 2 questions for paid work or schoolwork, 2 questions for household work, and 1 question for family, social and leisure activities. The 2 questions for each of the first two groups assess, respectively, the number of days off due to headache, and the number of days in which the productivity was reduced by half or more. mMIDAS total score was derived from the sum of the answers on the first 5 questions. Total score ranged from 0 (little/no disability) to 20 (severe disability) with higher scores indicating more severe disability.

The MSQ v2.1 is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0-to-100-point scale. Higher scores indicated better quality of life.

The MSQ v2.1 is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0-to-100-point scale. Higher scores indicated better quality of life.

The EQ-5D-5L VAS measures participant's self-rated health-related quality of life on a VAS. The VAS score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).

The EQ-5D-5L VAS measures participant's self-rated health-related quality of life on a VAS. The VAS score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).

The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.

The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.

The HADS is a participant-rated scale designed to assess psychological distress in non-psychiatric participants. The HADS consists of 2 sub-scales: depression and anxiety. Each sub-scale contains 7 items, and each item was rated from 0 (absent) to 3 (maximum severity). The total score of each sub-scale ranged from 0 (absent) to 21 (maximum severity). Higher scores indicated higher severity.

The HADS is a participant-rated scale designed to assess psychological distress in non-psychiatric participants. The HADS consists of 2 sub-scales: depression and anxiety. Each sub-scale contains 7 items, and each item was rated from 0 (absent) to 3 (maximum severity). The total score of each sub-scale ranged from 0 (absent) to 21 (maximum severity). Higher scores indicated higher severity.

TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

Number of participants who visited to a family doctor/general practitioner during the past 4 weeks has been reported at Baseline and Week 12.

Number of participants who visited a specialist during the past 4 weeks has been reported at Baseline and Week 12.

Number of participants who visited to the emergency department due to migraine during the past 4 weeks has been reported at Baseline and Week 12.

Number of participants who were admitted to the hospital during the past 4 weeks due to migraine has been reported at Baseline and Week 12.

Number of participants who had overnight hospital stays during the past 4 weeks due to migraine has been reported at Baseline and Week 12.

Number of participants who visited a family doctor/general practitioner has been reported.

Number of participants who visited a specialist has been reported.

Number of participants who visited the emergency department due to migraine has been reported.

Number of participants who admitted in the hospital due to migraine has been reported.

Number of participants with overnight hospital stays due to migraine has been reported.