Baseline characteristics of the enrolled patients with episodic cluster headache

During the study period, out of the fifty-two patients with episodic CH who were administered 240 mg of galcanezumab, twenty-seven experienced a relapse. And twenty-one patients who received 240 mg of galcanezumab again were included in the study. After excluding five patients according to criteria, sixteen patients with episodic CH, who received at least one dose of 240 mg galcanezumab, experienced recurrent cluster bout and were enrolled in this study. Of these, fourteen patients (87.5%) received at least one dose of 240 mg galcanezumab (two prefilled syringes each containing 120 mg) in consecutive episodes of cluster bouts, and the remaining two patients received a second treatment with galcanezumab during the pre-cluster period.

In the 14 patients who received galcanezumab treatment in two consecutive cluster bouts, the mean age was 38.1 ± 10.2 years. The mean onset age of CH was 26.4 ± 12.9 years and the median duration of CH disease before the 1st galcanezumab treatment was 3.1 (interquartile range, IQR 0.6,8.9) years (Table 1). Three patients (21%) were current smokers and five (36%) had a previous history of migraines. The average scores of PHQ-9 and GAD-7 were 12 and 10, respectively. Aspects of quality of life, the median EQ-5D scores was 0.9 (IQR, 0.7, 0.9), and no patient attempted suicide.

Table 1 Baseline characteristics of the 14 patients with episodic CH who received GT in different cluster boutsThe timing and kinds of preventive treatments in two consecutive episodes of cluster bouts

The median duration between 1st and 2nd galcanezumab treatments was 10.0 (IQR, 6.5, 17.5) months. The median duration of cluster bout period was 38.0 days in the first episode and 37.5 days in the second episode, respectively (Table 2). Galcanezumab was injected median 24.0 (IQR, 14.3, 34.3) days after the onset of the first episode of cluster bout and 11.0 (IQR, 5.0, 26.5) days in second episode (95% confidence interval [CI] -0.8 to 15.8, p = 0.071).

Table 2 The timing and kinds of preventive treatments in two consecutive episodes of cluster bouts (N = 14)

The numbers of patients who received galcanezumab treatment as the only preventives were 5 patients in the first episode and 4 patients in the second episode (p = 0.336). Regarding total preventives used during each episode of cluster bout, there were no differences in transitional therapy (50% in each episode) or conventional preventives (36% in each episode). Two patients during the first episode of cluster bout and 5 patients during the second episode of cluster bout received the follow-up galcanezumab treatment of 120 or 240 mg during the second month of cluster bout.

Regarding preventives before galcanezumab treatment, four patients received transitional therapy in the first episode and none of the patients received transitional therapy in the second episode of cluster bout (29% vs. 0%, p = 0.049). There were no differences in the proportion of each preventive therapy before the two episodes of cluster bout (36% vs.14%, p = 0.272). Regarding additional preventives treated after galcanezumab treatment, there were no differences in the proportions of patients receiving transitional (29% vs.50%, p = 0.272) and conventional (57% vs.71%, p = 0.336) preventives during each of the two episodes of cluster bout.

The proportions of patients with 50% or more reduction in daily headache frequency at week 3 from baseline were 86% and 64% during the first and second episodes of cluster bout (p = 0.192). Treatment responses, PGI-I, and adverse drug reaction were generally similar between the two episodes of cluster bout (Table 3). In the 1st episode of galcanezumab treatment, a decrease of five headache days in week 3 after galcanezumab treatment was noticed compared to that one week before treatment. In the 2nd episode of galcanezumab treatment, a decrease of three headache days at week 3 after galcanezumab treatment was observed during the same period (p = 0.004). No significant differences in the changes of daily headache frequency (-1.0 vs. -0.9, p = 0.965), total number of headaches (-7.0 vs.-6.0, p = 0.975), and VAS scores (-7.5 vs. -5.0, p = 0.251) were observed between the two galcanezumab treatment episodes. The improvement of PGI of galcanezumab treatment was reported as feeling “very much better” or “much better” in 86% and 64% patients in the first and second episodes, respectively. No serious adverse reactions or statistically significant differences in the frequency of adverse events according to the episodes of cluster bout were noticed.

Table 3 The clinical characteristics according to episode of cluster bout treated GT (N = 14)Two cases receiving galcanezumab treatment during the pre-cluster period

Two patients received the 2nd galcanezumab treatment during the pre-cluster period and did not experience cluster bout thereafter, and duration of the pre-cluster period was 60 days in case 1 and 10 days in case 2.

In case 1 (a 48-year-old, male), before the 1st galcanezumab treatment, the duration of cluster bout was usually 12 weeks. During the 1st galcanezumab treatment period, duration of the first cluster bout episode was 60 days after five days of the pre-cluster period, with a feeling of the upcoming cluster bout. After 11 months, the patient experienced the same pre-cluster symptoms for 14 days and received the 2nd galcanezumab treatment. The pre-cluster symptoms ended without typical CH 47 days after the 2nd galcanezumab treatment.

In case 2 (a 32-year-old, female), the usual duration of cluster bout was 11 weeks before the 1st galcanezumab treatment. She received 1st galcanezumab treatment 29 days after the onset of cluster bout, which ended 46 days after the 1st galcanezumab treatment. After 10 months, the patient experienced pre-cluster symptoms with a feeling of the upcoming cluster bout of very mild pain for eight days. She received the 2nd galcanezumab treatment, and her pre-cluster symptoms disappeared two days after the 2nd galcanezumab treatment without cluster bout.