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

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.