Figures and data in Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target – an fMRI study

4 figures, 4 tables and 2 additional files

Figures

Figure 1

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Figure 4

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Table 1

Patient characteristics	Galcanezumab	Erenumab
Number	26	27
Female, % (n)	96 (25)	81 (22)
Age, mean ± SD (range), in years	37.81±12.11 (21–60)	39.1±12.2 (22–60)
Disease duration, mean ± SD (range), in years	19.77±12.43 (2–50)	21.7±11.2 (6–43)
Headache frequency, mean ± SD (range), days/month EM: mean ± SD (range), days/month CM: mean ± SD (range), days/month	16.71±8.92 (4–30) 10.28±2.94 (4–14) 25.48±6.32 (16–30)	20.3±8.3 (8–30) 12.08±2.07 (8-14) 26.8±4.71(20–30)
Migraine with and without aura, n	7	9
Migraine without aura, n	19	18
Chronic migraine (ICHD-3), % (n)	42 (11)	56 (15)
Episodic migraine (ICHD-3), % (n)	58 (15)	44 (12)
Same headache state – episodic, % (n)	40 (6)	29 (5)
– chronic, % (n)	60 (9)	71 (12)

Abbreviation: ICHD-3=International Classification of Headache Disorders, 3rd edition, EM: episodic migraine, CM: chronic migraine.

Table 2

Anatomical region	Cluster size(voxels), n	T value	MNI coordinates(x,y,z)
*(A) Visit 1>visit 2, all participants (n=26, contrast* *[ammonia-air puffs]_visit1 > [ammonia-air puffs]_visit2,threshold: p<0.001 [uncorrected], T>3.45, minimum cluster extent 25 voxels, df = 25)*
R hypothalamus	49	4.99	8, –14, –7
R cerebellum	48	5.0	20, –40, –25
R cerebell. vermis	52	4.09	3, –67, –34
(B) Responder (n=8)>non-responder (n=7) with same headache state on both days *(contrast [ammonia-air puffs]_visit1 > [ammonia-air puffs]_visit2, threshold p<0.001 [uncorrected], T>3.85, minimum cluster extent 10 voxels, df = 14)*
R inf. parietal lobule	91	9.17	58, –44, 21
L precentral gyrus	26	5.99	−48, –11, 11
L parahippocampal gyrus	12	5.06	−18, –11, –19
L superior temporal gyrus	13	4.76	–36, 15,–26
L inf. parietal lobule	17	4.7	46, –42, 22
R lentiform nucleus	16	4.67	24, –2, 4
R parahippocampal gyrus	27	4.63	27, –28, –12
L insula	26	4.56	−45, –27, 19
L hypothalamus	13	4.47	−6, –17, –6

(A) Main findings of trigeminal pain processing alterations after administration of the CGRP-ligand monoclonal antibody galcanezumab. The contrast shows more neuronal activity on visit 1 than on visit 2, therefore decrease driven by galcanezumab and was tested with a one-way paired t-test. (B) Subgroup analysis of patients having the same migraine/headache state on both visits (ictal and ictal or interictal and interictal). Main findings specific for being responder (responder showing a higher decrease after galcanezumab than non-responder) tested with a one-way independent sample t-test. Note that left-right activation patterns in near proximity twin structures such as the hypothalamus are not necessarily side-locked (a left activation excludes a right activation) but may be due to statistical thresholding.

Table 3

Anatomical region	Cluster size(voxels), n	T value	MNI coordinates(x,y,z)
(A) Erenumab >Galcanezumab (Visit 1>visit 2, migraine-phase equal subgroup [n=15 vs. n=17], contrast [ammonia-air puffs]_visit1 > [ammonia-air puffs]_visit2,threshold: p<0.001 [uncorrected], T>3.39, minimum cluster extent 10 voxels, df = 30)
L operculum	416	5.61	−60, –5, 8
L cerebellum	122	5.59	−16, –65, –22
R cerebellum	207	5.23	42, –51, –32
R supramarginal gyrus	37	5.11	64, –45, 23
R thalamus	67	5.0	6, –15, 11
R hippocampus	74	4.88	21, –32, –10
L thalamus	53	4.71	−9, –7, 11
L temporal pole/insula	202	4.5	–54, 17, –1
L superior temporal gyrus	55	4.42	−55, –33, 16
Locus coeruleus	30	4.41	4, –37, –9
R insula	82	4.37	47, 14, –7
R operculum	19	4.15	62, –2, 7
R middle temporal gyrus	21	4.07	55, –6, –22
R lingual gyrus	11	3.9	16, –49, 0

(B) Galcanezumab >Erenumab (Visit 1>visit 2, migraine-phase equal subgroup [n=15 vs. n=17], contrast [ammonia-air puffs]_visit1 > [ammonia-air puffs]_visit2,threshold: p<0.001 [uncorrected], T>3.39, minimum cluster extent 10 voxels, df = 30)
Pons	40	4.09	−1, –18, –38
R substantia nigra	13	4.01	9, –14, –10
L thalamus	13	3.93	−18, –15, 0
R hypothalamus	12	3.89	4, –19, 0

Main findings of trigeminal pain processing alterations driven by the administration of the CGRP receptor monoclonal antibody erenumab in contrast to the CGRP ligand monoclonal antibody galcanezumab in the migraine-phase equal subgroup. (A) Erenumab-specific decrease in neuronal activity/BOLD across the two visits. (B) Galcanezumab-specific decrease in neuronal activity/BOLD across the two visits. Both results stem from one-sided independent t-tests.

Table 4

Anatomical region	Cluster size(voxels), n	T value	MNI coordinates(x,y,z)
(A) Covariation of monthly headache day reduction (in % reduction) in the contrast (ammonia-air puffs) _visit1, all participants (n=26) threshold: p<0.001 [uncorrected], T>3.48, minimum cluster extent 25 voxels, df = 25
R middle temporal gyrus	110	4.9	49, –8, –14
STN	83	4.65	4, –42, –53
(B) PPI analysis of STN (region of interest 4, −42,–53), all participants (n=26) in the contrast (ammonia-air puffs) _visit1> [ammonia-air puffs]_visit2, threshold: p<0.001 [uncorrected], T>3.45, minimum cluster extent 25 voxels, df = 25
L superior temporal gyrus	62	5.57	−52, –47, 18
R hyopthalamus	52	4.24	10, 5, –12

(A) Main findings of the covariation of the response to galcanezumab by the activation pattern of neuronal activity at visit 1 (before administration of galcanezumab). This result was gained by introducing the covariate of reduction in headache days into a one-sided, one-sample t-test. (B) Results from the psychophysiological interaction analysis of the above-mentioned STN activation.