Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation

Abstract

Objective: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved.

Background: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need.

Methods: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months.

Results: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients).

Conclusions: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.

Keywords: calcitonin gene-related peptide monoclonal antibody; headache; idiopathic intracranial hypertension; papilledema; raised intracranial pressure.

FIGURE 1

Flowchart of patient recruitment and follow‐up

FIGURE 2

Effect of erenumab on key end points. (A) Change in mean number of monthly moderate/severe headache days from baseline to 3, 6, 9, and 12 months. Error bars represent 95% Confidence intervals (CIs). (B) Percentage change in mean number of monthly moderate/severe headache days from baseline to 3, 6, 9, and 12 months. Error bars represent 95% CIs. (C) Percentage of patients with at least a 30%, 50%, and 75% reduction in their monthly moderate/severe headache days from baseline to 3, 6, 9, and 12 months (responder rates). Number above bars represents the percentage of patients. (D) Change in mean number of monthly total headache days from baseline to 3, 6, 9, and 12 months. Error bars represent 95% CIs. (E) Percentage change in mean number of monthly total headache days from baseline to 3, 6, 9, and 12 months. Error bars represent 95% CIs. (F) Percentage of patients with at least a 30%, 50%, and 75% reduction in their monthly total headache days from baseline to 3, 6, 9, and 12 months (headache responder rates). Number above bars represents the percentage of patients. (G) Mean number of absenteeism and presenteeism days as reported by patients at baseline and at 3, 6, 9, and 12 months. Error bars represent 95% CIs. (H) Mean number of analgesic days at baseline and at 3, 6, 9, and 12 months. Error bars represent 95% CIs. (I) Mean headache impact test‐6 (HIT‐6) score at baseline and at 3, 6, 9, and 12 months. Error bars represent 95% CIs. MHD, monthly total headache days; MICD, minimally important clinical difference; MmsHD, monthly moderate/severe headache days. ***p < 0.001 compared to baseline, **p < 0.01 compared to baseline, *p < 0.05 compared to baseline [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Effect of erenumab on headache in those with and without previous migraine and medication overuse headache. Change in mean number of monthly moderate/severe headache days from baseline to 3, 6, 9, and 12 months. Error bars represent 95% confidence intervals (CIs). (A) Patients with migraine diagnosis prior to IIH diagnosis. (B) Patients without migraine diagnosis prior to IIH diagnosis. (C) Patients with MOH at baseline. (D) Patients without MOH at baseline. IIH, idiopathic intracranial hypertension; MOH, medication overuse headache. ***p < 0.001 compared to baseline [Color figure can be viewed at wileyonlinelibrary.com]