Migraine Prevention with Erenumab: Focus on Patient Selection, Perspectives and Outcomes

Figures & data

Figure 1 Mechanisms of action of monoclonal antibody (mAb) targeting Calcintonine Gene-related peptide (CGRP) receptor (erenumab) and antibodies targeting the soluble CGRP at synaptic level and representation of CGRP receptor and (amylin) AMY1 receptor. Created with BioRender.com.

Table 1 Main Baseline Characteristics and Outcomes of the Randomized Clinical Trials

Study, year, NCT	Country	DB follow-up, weeks	Disease duration, mean years ± SD, treatment Vs placebo	Sample size, treatment Vs placebo	Migraine form	Mean age ± SD	Female sex, %	MMDS/MHDs difference from baseline, treatment Vs placebo	AMDs difference from baseline, treatment Vs placebo
Sun et al 2016 NCT01952574^Citation16	North America and Europe	12	19.0 ± 11.4 7 mg, 20.1 ± 12.5 21 mg, 21.5 ± 1.7 70 mg, 20·7 ±11·5	108 7 mg; 108 21 mg; 107 70 mg, 160	EM	40.3±10.9 7 mg, 39.9±12.3 21 mg, 42.6 ±9.9 70 mg, 41.4±10·0	81 7 mg, 81 21 mg, 77 70 mg, 83	2.2 ± 0.4 7 mg; 2.4 ± 0.4 21 mg; 3.4 ± 0.4 70 mg; 2.3 ± 0.3	1.2 70 mg
Sakai et al 2019 NCT02630459^Citation17	Japan	24	NA	67 28 mg, 135 70 mg, 137 140 mg, 136	EM	45 (21-61) 28 mg, 43 (22-57) 70 mg, 44 (20-64) 140 mg, 45 (23-64)	82.1 28 mg, 85.2 70 mg, 81.8 140 mg, 86.8	1.19 (1.9-0.4) 28 mg 2.25 (3-1) 70 mg, 1.83 (2.3-1.3) 140 mg, 0.06 (0.4-0.5)	0.19 (0.8–0.43) 28 mg, 1.07 (1.8-0.8) 70 mg, 1.16 (1.6-0.7) 140 mg, 0.8 (0.4-1.3)
Goadsby et al 2017 NCT02456740^Citation27 (STRIVE)	North America, Europe and Turkey	24	NA	317 70 mg, 319 140 mg, 319	EM	41.1±11.3 70 mg, 40.4±11.1 140 mg, 41.3±11.2	84.5 70 mg, 85.3 140 mg, 85.9	3.2±0.2 70 mg, 3.7±0.2 140 mg, 1.8±0.2	1.1 ± 0.1 70 mg, 1.6 ± 0.1 140 mg, 0.2 ± 0.1
Tepper et al 2017 NCT02066415^Citation18	North America and Europe	12	20.7 ±12.8 70 mg, 21.9 ±11.8 140 mg 22.2 ±12.6	191 70 mg, 190 140 mg 286	CM	41.4±1.3 70 mg, 42.9±11.1 140 mg, 42.1±11.3	87 70 mg, 84 140 mg, 79	6.6±0.4 70 mg, 6.6±0.4 140 mg, 4.2±0.4	3.5 (0.3) 70 mg, 4.1 (0.3) 140 mg, 1.6 (0.2)
Dodick et al 2018 NCT02483585^Citation19 (ARISE)	North America and Europe	12	22 ±13 70 mg 20 ± 12	286 70 mg 291	EM	42 ± 11 70 mg, 42 ±12	85.7 70 mg, 84.9	2.9 ± 0.2 70 mg, 18 ± 0.2	1.2 ± 0.1 70 mg, 0.6 ± 0.1
Reuter et al 2018 NCT03096834^Citation28(28) (LIBERTY)	Europe and Australia	12	NA	121 140 mg 125	EM	44.2 ± 10.6 140 mg 44.6 ± 10.5	80 140 mg, 81	1.8 ±0.4 140 mg, 0.2 ± 0.4	1.3 ± 0.2 140 mg, 0.5 ± 0.3

Abbreviations: AMDs, monthly acute medication days; CM, chronic migraine; DB, double blind; EM, episodic migraine; MMDs, monthly migraine days; MHD, monthly headache days; NA, not available; SD, standard deviation.

Figure 2 (A) 12-week reduction in monthly migraine days (MMDs) from baseline in placebo-controlled randomized trials. (B) 12-week reduction in monthly migraine days (MMDs) from baseline in real-world studies. Data were derived from MMDs at baseline and MMDs at week 12 of treatment provided by the studies.

Table 2 Main Baseline Characteristics and Outcomes of the Real-World Studies

Study, Year	Country	Months of Follow-Up	Disease Duration, Mean Years ± SD	Sample Size	Migraine Forms, % of Patients	Mean Age ± SD	Female Sex, %	Medication Overuse (% of Patients)	Mean Prior Treatment Failures ±SD/(IQR)	MMDS/MHDs Difference from Baseline at Week 12	AMDs Difference From Baseline at Week 12
Barbanti et al, 2019^Citation37	Italy	2	5.13±1.8 EM, 5.4±2.6 CM	78	16.7 EM, 84 CM	47 ±14.4 EM, 47.1±10 CM	71	61.5 EM, 84.6 CM	29.1±15.3 EM, 30.2±11.7 CM	NA	NA
Raffaelli et al, 2020^Citation56	Germany	3	NA	139	100 CM	53.4±10.2	83.5	NA	3.6±1.2 plus BoNTA	4.5*	6.3*
Lambru et al, 2020^Citation38	UK	6	13±11.9	162	100 CM	46±13	83.3	54	8.4±3.6	6*	8.2*
Russo et al, 2020^Citation39	Italy	6	33.1±1.2	70	100 CM	46.9±1.4	78.6	91.4	4.7±0.3	9.7*	NA
Ornello et al, 2020^Citation40	Italy	6	28.2±13.3	89	5.6 EM, 94.4 CM	46.8±11.2	87.6	71.9	3.23	12*	8*
Scheffler et al, 2020^Citation41	Germany	3	NA	100	26 EM, 74 CM	52.9±9.1 EM 45.8±12.9 CM	88.4 EM 91.2 CM	66 CM	NA	2.5*	3.6*
Robblee et al, 2020^Citation55	US	6	NA	101	5.9 EM, 94.1 CM	49 (18–80)	89.1	18.8	NA	8.4 ±5.8–11.1	NA
Ranieri et al, 2020^Citation44	Italy	12	NA	30	30 EM, 70 CM	44±11.5	90	28.5	NA	7.7*	6*
Pensato et al, 2020^Citation45	Italy	3	18.9±10.1	39	100 CM	49.8±8.3	64	100	13 (11–16)	13*	12*
Matteo et al, 2020^Citation53	Italy	6	33.6±11.8	159	23.3 EM 76.7 CM	50.23±9.4	75	91 CM	6.9±2.7	4.8*	11.7*
Della Valle et al, 2020^Citation54	Italy	10	NA	40	45 EM 55 CM	45.2±7.4	75	52.5	NA	NA	NA
Barbanti et al 2020 (EARLY)^Citation46	Italy	3	28.2±12.4 EM, 30.7 ± 12.2 CM	372	103 EM, 269 CM	47.5±11.4 EM, 48.4±10.2 CM	71.8 EM, 78.1 CM	37.9 EM, 85.1 CM	3.4 ± 2 EM, 5.1 ± 2.7 CM	4.5 ± 4.1 EM, 9.3±9.1 CM	7 EM, 12 CM
Eghtesadi et al, 2021^Citation49	Canada	12	32.9 ± 11.4	18	33.3 EM 66.7 CM	48.7±7	83.3	58.3 CM	4.3±1.3	5.2±6.9	5.4±7.0
Cainazzo et al, 2021^Citation50	Italy	12	33.17 ± 11.57	81	100 CM	49.58±9.52	80.2	100	5.75±3.17	6*	6.8*
Storch et al, 2021^Citation51	Germany	6	NA	82	42.7 EM, 57.3 CM	51.1±10.5	83	53.9	4.49±1.33	5.24±5.64	NA
de Vries Lentsch, 2021^Citation52	Netherlands	6	NA	100	54 EM 46 CM	43±12	85	NA	5.0±1.0	3.8*	NA

Abbreviations: AMDs, monthly acute medication days; BoNTA, botulinum toxin A; CM, chronic migraine; EM, episodic migraine; IQR, interquartile range; MMDs, monthly migraine days; MHD, monthly headache days; NA, not available; SD, standard deviation; US, United States; asterisk marks data calculated.

Figure 3 Most common adverse events occurring during the use of erenumab. Created with BioRender.com.

Figure 4 Comparison between overall patients’ characteristics of randomized controlled trials and real-world studies.

Abbreviation: MMDs-monthly migraine days. Created with BioRender.com.

Table 3 Ongoing Phase 3 and 4 Randomized Controlled Studies

NCT	Country	Comparator	Aim	Primary Endpoint	Sample Size, N of Patients	Migraine Form	Age, Years
NCT03927144	US	Oral preventatives	Superiority of erenumab to oral preventatives	Treatment completion with a >50% response rate at month 12	621	EM	>18
NCT04252742 (EMBRACE)	US	Placebo	Treatment benefit on duration of moderate headache	Change in mean monthly hours of at least moderate headache pain intensity (11-point NRS scale)	576	High frequency EM	>18
NCT03867201 (DRAGON)	China	Placebo	Efficacy and safety of erenumab in Asian patients with chronic migraine	Changes in MMDs during the last 4 weeks of a 12-week treatment	557	CM	18–65
NCT03836040 NCT03832998	US	Placebo	Efficacy and safety of erenumab in children and adolescents	Changes in MMDs	456 EM 286 CM	EM CM	6–12 12–18
NCT04452929	Denmark	Placebo	Effect of erenumab in calcitonin-gene related peptide and cilostazol human experimental models of migraine	Incidence of migraine-like attacks	72	EM/CM	18–60
NCT03971071	US	Placebo	Efficacy and safety of erenumab in patients with chronic migraine and medication overuse	Number of participants with absence of Medication Overuse Headache at month 6	687	CM	>18

Abbreviations: CM, chronic migraine; EM, episodic migraine; MMDs, monthly migraine days; NRS, numerical rating scale; US, United States.

Table 4 Ongoing Open-Label Studies

NCT	Country	Aim	Primary Endpoint	Sample Size, N of Patients	Migraine Form	Age, Years
NCT03773562	US	Changes in brain function and structure under erenumab treatment	Changes in Pain-Induced Brain Activations and Brain Functional Connectivity (MRI)	50	EM	18–65
NCT04361721	Italy	Impact of erenumab treatment on neurophysiological, biomolecular and psychological aspects	Spinal sensitization measured as TST of the nociceptive withdrawal reflex	40	CM	18–65
NCT04592952	Denmark	Relationships between clinical response to erenumab and response to intravenous infusion of calcitonin CGRP	Headache diaries (migraine days, headache days, number of days with use of acute migraine medication, number of days with aura)	400	EM/CM	18–50
NCT04265755 INTERROGATE	Denmark, Iceland	Relationships between clinical response to erenumab and genetic biomarkers	>50% response rate in those with SNPs contributing to the migraine polygenic risk score	2000	EM/CM	>18
NCT04659226	Italy	Expression profiles of microRNAs before and after erenumab treatment	Changes in microRNA serum concentration	40	EM	25–50
NCT04084314	Germany	Long-term safety and tolerability (128 weeks) of erenumab treatment	Adverse events	699	EM/CM	18–60

Abbreviations: CM, chronic migraine; CGRP, Calcitonin gene-related peptide; EM, episodic migraine; MRI, magnetic resonance imaging; N, number of patients; SNP, single nucleotide polymorphism; TST, temporal summation threshold; US, United States.

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