Background
Methods
Study design and participants
Eligibility criteria
Description of the variables and outcome measures
Demographic and clinical variables
Preventive, symptomatic and concomitant pharmacological treatments
Healthcare resource use, sick leave and associated costs
Definitions and outcomes measures
-
Persistence time or duration of treatment, including:
-
◦ The elapsed time from the index date until treatment discontinuation or the end of the study, whichever came first. Discontinuation implied either permanent treatment dropout or reinitiation of the same or another treatment (after 60 days). Treatment switching between different prophylactic medications or dose increase/decrease within 60 days or less since the last prescription were not considered discontinuation events since it is common clinical practice [28]. The 60-day gap period was defined in accordance with other publications and expert opinion.
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◦ 6- and 12-month persistent rates: percentage of patients who persisted with their preventive treatment until day 183 and day 365 after the index date. Persistence was defined as the prescribed treatment continuation or switching during the study follow-up period, either with or without dose adjustments.
-
-
Prescription patterns:
-
◦ Switching events: percentage of patients who changed their preventive medication within 60 days from the last prescription. Reinitiation events: percentage of patients who restarted the same or another medication after a gap of 60 days or more since the last prescription.
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Statistical analysis
Results
Study population and baseline characteristics
Entire study population
N = 7,866 (100%) | Non-persistent patients
N = 5,414 (69.4%) | Persistent patients
N = 2,390 (30.6%) | |
---|---|---|---|
Age, years | |||
Mean (SD) | 48.2 (14.8) | 47.6 (14.7) | 48.8 (14.3) |
Age range, n (%) | |||
18—44 years | 3,296 (41.9%) | 2,343 (43.3%) | 949 (39.6%) |
45—64 years | 3,527 (44.8%) | 2,384 (44.1%) | 1,127 (47.1%) |
65—74 years | 713 (9.1%) | 479 (8.9%) | 223 (9.3%) |
≥ 75 years | 330 (4.2%) | 204 (3.8%) | 95 (4.0%) |
Gender (women), n (%) | 6,324 (80.4%) | 4,361 (80.6%) | 1,918 (80.3%) |
BMI, kg/m2 | |||
Mean (SD) | 27.8 (4.5) | 27.7 (4.5) | 27.9 (4.3) |
Time since diagnosis, yearsa | |||
Mean (SD) | 3.6 (1.9) | 3.6 (1.9) | 3.7 (1.9) |
Comorbidities per patient
| |||
Mean (SD) | 1.6 (1.4) | 1.6 (1.4) | 1.6 (1.4) |
CCI
| |||
Mean (SD) | 0.4 (0.9) | 0.4 (0.9) | 0.4 (0.9) |
Comorbidities, n (%) | |||
Generalized anxiety disorder | 2,827 (35.9%) | 1,968 (36.4%) | 813 (34.0%) |
Dyslipidaemia | 2,124 (27.0%) | 1,445 (26.7%) | 648 (27.1%) |
Arterial hypertension | 1,724 (21.9%) | 1,170 (21.6%) | 524 (21.9%) |
Obesity | 1,161 (14.8%) | 794 (14.7%) | 353 (14.8%) |
Depressive syndrome | 890 (11.3%) | 607 (11.2%) | 272 (11.4%) |
Asthma | 622 (7.9%) | 450 (8.3%) | 166 (6.9%) |
Malignant neoplasms | 620 (7.9%) | 439 (8.1%) | 168 (7.0%) |
Diabetes | 529 (6.7%) | 397 (7.3%) | 118 (4.9%) |
COPD | 220 (2.8%) | 154 (2.8%) | 63 (2.6%) |
Stroke | 170 (2.2%) | 112 (2.1%) | 55 (2.3%) |
Ischaemic heart disease | 115 (1.5%) | 69 (1.3%) | 41 (1.7%) |
Kidney failure | 121 (1.5%) | 85 (1.6%) | 30 (1.3%) |
Heart failure | 99 (1.3%) | 62 (1.1%) | 31 (1.3%) |
Other risk factors, n (%) | |||
Active smoking | 1,426 (18.1%) | 922 (17.0%) | 478 (20.0%) |
Prescription of migraine treatments and involved healthcare professionals
Non-persistent patients
N = 5,414 (69.4%) | Persistent patients
N = 2,390 (30.6%) | |
---|---|---|
Medical specialty or service, n (%) | ||
Primary Care | 4,093 (75.6%) | 1,896 (79.3%) |
Neurology | 893 (16.5%) | 324 (13.5%) |
Psychiatry | 146 (2.7%) | 62 (2.6%) |
A&E | 65 (1.2%) | 24 (1.0%) |
Internal Medicine | 27 (0.5%) | 12 (0.5%) |
Others | 190 (3.5%) | 72 (3.0%) |
Healthcare resource use and associated costs
Non-persistent patients
N = 5414 (69.4%) | Persistent patients
N = 2390 (30.6%) | Difference (Persistent – Non-persistent)
N = 7866 | |
---|---|---|---|
Primary Care visits
| |||
- Mean (SD) | 12.0 (8.8) | 9.0 (8.7) | -2.98 |
- CI 95% | (11.8;12.2) | (8.7;9.4) | (-3.41; -2.56) |
- Median (P25–P75) | 10 (6–15) | 6 (3–12) | |
- Min-Max | 0–59 | 0–59 | |
Specialist visits
| |||
- Mean (SD) | 2.2 (1.1) | 1.1 (0.9) | -1.07 |
- CI 95% | (2.1;2.2) | (1.1;1.1) | (-1.12; -1.01) |
- Median (P25–P75) | 2 (1–3) | 1 (1–1) | |
- Min-Max | 0–10 | 0–10 | |
A&E admissions
| |||
- Mean (SD) | 1.3 (2.2) | 0.5 (1.2) | -0,86 |
- CI 95% | (1.3;1.4) | (0.4;0.5) | (-0.95; -0.76) |
- Median (P25–P75) | 0 (0–5) | 0 (0–0) | |
- Min-Max | 0–5 | 0–5 | |
Hospital stays
| |||
- Mean (SD) | 0.2 (1.4) | 0.1 (1.3) | -0.03 |
- CI 95% | (0.1;0.2) | (0.1;0.2) | (-0.1; 0.03) |
- Median (P25–P75) | 0 (0–0) | 0 (0–0) | |
- Min-Max | 0–44 | 0–22 | |
Laboratory tests
| |||
- Mean (SD) | 1.4 (1.2) | 0.7 (1.1) | -0.67 |
- CI 95% | (1.4;1.4) | (0.7;0.8) | (-0.72; -0.61) |
- Median (P25–P75) | 1 (0–2) | 0 (0–1) | |
- Min-Max | 0–4 | 0–4 | |
Conventional radiology
| |||
- Mean (SD) | 1.1 (1.5) | 1.0 (1.4) | -0.08 |
- CI 95% | (1.0;1,1) | (0.9;1.0) | (-0.15: -0.01) |
- Median (P25–P75) | 0 (0–2) | 0 (0–2) | |
- Min-Max | 0–5 | 0–5 | |
CT scan
| |||
- Mean (SD) | 0.1 (0.3) | 0.1 (0.2) | -0.02 |
- CI 95% | (0.1;0.1) | (0;0.1) | (-0.03;0) |
- Median (P25–P75) | 0 (0–0) | 0 (0–0) | |
- Min-Max | 0–3 | 0–2 | |
MRI
| |||
- Mean (SD) | 0.1 (0.4) | 0.1 (0.4) | -0.01 |
- CI 95% | (0.1;0.1) | (0.1;0.1) | (-0.03;0.01) |
- Median (P25–P75) | 0 (0–0) | 0 (0–0) | |
- Min-Max | 0–5 | 0–5 | |
Other tests
| |||
- Mean (SD) | 1.2 (1.2) | 1.0 (1.1) | -0.16 |
- CI 95% | (1.2;1.2) | (1.0;1.1) | (-0.22; -0.1) |
- Median (P25–P75) | 1 (0–2) | 1 (0–2) | |
- Min-Max | 0–5 | 0–5 | |
Days of sick leave
| |||
- Mean (SD) | 14.7 (38.8) | 12.0 (37.4) | -2.69 |
- CI 95% | (13.7;15.8) | (10.5;13.5) | (-4.54; -0.84) |
- Median (P25–P75) | 1 (1–11) | 0 (0–4) | |
- Min-Max | 0–365 | 0–365 |
Non-persistent patients
N = 5414 (69.4%) | Persistent patients
N = 2390 (30.6%) | Difference (Persistent – Non-persistent)
N = 7866 | |
---|---|---|---|
Health servicesa, € patient-year | |||
Primary Care visits, | |||
Mean (SD) | 278.1 (204.1) | 208.9 (200.9) | -69.2 |
95% CI | (-79.0; -59.4) | ||
Specialist visits
| |||
Mean (SD) | 199.4 (104.4) | 100.7 (87.8) | -98.7 |
95% CI | (-103.5; -93.9) | ||
A&E admissions
| |||
Mean (SD) | 156.9 (259.2) | 56.2 (135.3) | -100.7 |
95% CI | (-111.7; -89.7) | ||
Hospital stays
| |||
Mean (SD) | 76.2 (681.4) | 59.8 (628.0) | -16.5 |
95% CI | (-48.5; 15.6) | ||
Medical testsb, € patient-year | |||
Laboratory tests
| |||
Mean (SD) | 45.2 (38.7) | 23.6 (34.4) | -21.6 |
95% CI | (-23.4; -19.8) | ||
Conventional radiology
| |||
Mean (SD) | 30.2 (41.4) | 28.0 (40.2) | -2.2 |
95% CI | (-4.2; -0.2) | ||
CT scan
| |||
Mean (SD) | 6.4 (26.0) | 4.9 (22.5) | -1.5 |
95% CI | (-2.7; -0.3) | ||
MRI
| |||
Mean (SD) | 21.7 (77.0) | 19.5 (72.4) | -2.2 |
95% CI | (-5.9; 1.4) | ||
Other tests
| |||
Mean (SD) | 55.9 (57.0) | 48.4 (50.4) | -7.5 |
95% CI | (-10.2; -4.9) | ||
Medicationc, € patient-year | |||
Symptomatic medication
| |||
Mean (SD) | 254.8 (769.4) | 257.7 (933.3) | 2.9 |
95% CI | (-36.7; 42.5) | ||
Preventive medication
| |||
Mean (SD) | 155.9 (368.1) | 152.3 (373.6) | -3.5 |
95% CI | (-21.3; 14.3) | ||
Concomitant medication
| |||
Mean (SD) | 162.0 (389.4) | 141.5 (437.9) | -20.5 |
95% CI | (-40.0; -1.0) | ||
Total healthcare direct costs, € patient-year | |||
Mean (SD) | 1,476.8 (1,472.9) | 1,127.1 (1,521.4) | -349.8 |
95% CI | (-421.4; -278.1) | ||
Non-healthcare indirect costs, € patient-yeard | |||
Mean (SD) | 1,490.0 (3,930.0) | 1,217.7 (3,786.4) | -272.3 |
95% CI | (-459.4; -85.2) | ||
Total costs, € patient-year | |||
Mean (SD) | 2,966.8 (4,352.6) | 2,344.8 (4,189.1) | -622.1 |
95% CI | (-829.2; -414.9) | ||
Adjusted costs, € patient-yeare | |||
Mean | 2,929.0 | 2,346.0 | -583.0 |
(95% CI) | (2,784.0;3,073.0) | (2,130.0;2,562.0) | (-708.0; -458.0) |
Persistence and risk of discontinuation to migraine preventive treatment
From the 1st line
|
From the 2nd line
|
From the 3rd or higher
| |||||||
---|---|---|---|---|---|---|---|---|---|
HR | SD |
P
| HR | SD |
P
| HR | SD |
P
| |
Agea |
5.06
|
< 0.001
|
< 0.001
|
5.10
|
< 0.001
|
< 0.001
| 5.09 | 0.01 | 0.237 |
Gender
| 0.98 | 0.03 | 0.526 | 0.87 | 0.19 | 0.455 | 1.09 | 0.55 | 0.882 |
CCI
| 1.01 | 0.01 | 0.516 | 0.95 | 0.09 | 0.582 | 1.01 | 0.28 | 0.96 |
Time since diagnosis
| 0.99 | 0.01 | 0.048 | 0.97 | 0.04 | 0.432 | 1.04 | 0.11 | 0.730 |
Discontinuation (vs. 1st line)
| n/a |
0.24
|
0.35
|
< 0.001
| 0.21 | 0.98 | 0.110 |