Evaluate use of concomitant acute and preventive treatments with galcanezumab (GMB) in adults with chronic cluster headache (CH) as defined in ICHD-3 beta.

Chronic CH is a disabling neurological disorder. This phase 3 study evaluated GMB, a humanized monoclonal antibody that binds to calcitonin gene-related peptide, for prevention of CH attacks in adults with chronic CH.

Data are from phase-3, double-blind, placebo-controlled trial with a prospective baseline (BL), 12-week treatment-period, and 12-month open-label extension. Patients, randomized to monthly subcutaneous (SC) GMB-300mg (N=117) or placebo (PBO) (N=120). Certain acute treatments and up to 6 pre-specified preventives were allowed. While the primary endpoint was not met, subgroup analyses investigated potential influences of acute and preventive treatments.

Of 150 patients who used preventive treatment at BL, 72% used one preventive and 24% used two. Preventive use was stable during treatment with similar frequency between GMB and PBO-treatment groups. Verapamil was most common (50%), then lithium-(13%), topiramate-(9%), valproate-(6%), gabapentin-(3%), and melatonin-(3%). Pre-specified subgroup analysis for the primary efficacy measure showed no significant subgroup-by-treatment interaction by BL verapamil use (interaction p-value=0.64), as did a post-hoc subgroup analysis based on any preventive use.

Patients most commonly used SC sumatriptan (62.9%) and oxygen (59.1%) for acute treatment during BL and also in treatment phase (SC sumatriptan: GMB:67.5%; PBO:67.5% and oxygen: GMB:65.0%; PBO:53.3%). There were no statistically significant differences between treatment groups for any acute treatment. Post-hoc analysis showed greater mean reduction in weekly attack frequency for GMB versus PBO in patients with high-frequency (>7 weekly uses) BL SC sumatriptan use compared to low-frequency users (interaction p-value=0.033).

Overall, GMB-treated patients reported more treatment-emergent adverse events, including injection-site-erythema (GMB:7%;PBO:1%,p=.018).

Oxygen and SC sumatriptan were most common acute treatments. While up to 6
preventive-treatments were allowed, most patients used one preventive, and verapamil was by far the most common choice.