Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension

Abstract

Background: Headache is the dominant factor for quality of life related disability in idiopathic intracranial hypertension (IIH) and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet clinical need.

Case series: We report a series of seven patients in whom headaches were the presenting feature of IIH and the headaches had migraine-like characteristics, as is typical in many IIH patients. Papilloedema settled (ocular remission) but headaches continued. These headaches responded markedly to erenumab, a monoclonal antibody targeted against the calcitonin gene related peptide (CGRP) receptor. Of note, there was a recurrence of raised ICP, as evidenced by a return of the papilloedema, however the headaches did not recur whilst treated with erenumab.

Conclusions: Those with prior IIH who have their headaches successfully treated with CGRP therapy, should remain under close ocular surveillance (particularly when weight gain is evident) as papilloedema can re-occur in the absence of headache. These cases may suggest that CGRP could be a mechanistic driver for headache in patients with active IIH.

Keywords: CGRP monoclonal antibody; Headache; Idiopathic intracranial hypertension; Papilloedema; Raised intracranial pressure.

Fig. 1

Headache days, BMI and optical coherence testing of patients. a Monthly moderate/severe headache days (MmsHD) at clinical assessment time-points. Each patient is represented by different colour. Relapse point is represented by empty circle or triangle large point for each patient. b Mean number of monthly moderate/severe headache days (MmsHD) and total monthly headache days (MHD) at − 12 months, erenumab initiation (0 months), 3 months and at relapse. Error bars represent standard error of the mean (SEM). T-test performed for changes compared to erenumab initiation for MmsHD and Wilcoxon signed ranks test performed for changes compared to erenumab initiation for MHD. ***P < 0.001 compared to erenumab initiation, ** P < 0.01 compared to Erenumab initiation, * P < 0.05 compared to Erenumab initiation. c Body mass index percentage change at time of relapse compared to erenumab initiation (substantial fluctuations in weight were possible in between formal clinical assessments, but were not measured). Each patient is represented by different colour. d Optical coherence tomography (OCT) global average peripapillary retinal nerve fibre layer (pRNFL) thickness at clinical assessment time-points (0 months represents erenumab initiation time-point). Each patient is represented by different colour. e Infrared image of the right eye at erenumab initiation (Heidelberg Engineering SPECTRALIS, Heidelberg, Germany) for Patient 2 (P2). This shows no papilloedema. f Infrared image of the right eye at 6 months Patient 2 (P2). This shows recurrence of papilloedema. g Graph of OCT cross-sectional pRNFL thickness derived from 12° ring scan centred on the optic disc (Heidelberg Engineering SPECTRALIS, Heidelberg, Germany) for Patient 2 (P2). Black line shows the cross-sectional pRNFL thickness of the six-month scan (relapse), with the grey line showing the same information for the erenumab initiation scan. The difference between these lines (red arrows) indicates the magnitude of increase in pRNFL thickness between these scans, demonstrating relapse of IIH and recurrence of active papilloedema. The shaded green area indicates the proprietary ‘normal’ range for pRNFL thickness. Abbreviations: MmsHD, Monthly moderate/severe headache days; MHD, Monthly headache days; OCT, Optical coherence testing; RNFL, retinal nerve fibre layer; TMP, Temporal; SUP, Superior; NAS, Nasal; INF, Inferior