Selection of enrolled patients, baseline characteristics, and prevention with Galcanezumab therapy
Fifty patients with CH who received at least 1 dose of 240 mg (2 prefilled syringe of 120 mg) of galcanezumab were enrolled during our study period. Two patients with chronic CH and one patient during his first cluster episode were excluded from the analysis for the GT efficacy in episodic cluster headache (ECH) (Fig. 1).
The mean age of the 47 patients with ECH was 40.4 (range 25–61) years and they had experienced 2–28 bouts before the current bout. The 47 patients were comprised of 39 males (83.0%) and 8 females. Thirteen patients (27.7%) had a previous history of migraines.
Regarding the timing of GT for current cluster bout: 36 patients added the GT on their conventional preventive therapy (CPT) and 11 patients started GT as their initial preventive therapy. In the initial GT group, mean onset age of CH was about 5 years younger and disease duration of cluster headache was somewhat longer than GT with CPT group. However, there was no significant difference of baseline characteristics between the two groups (Table 1).
Table 1
Baseline characteristics of the patients with episodic cluster headache according to the timing of 240 mg of galcanezumab therapy (GT)
|
GT adds on CPT
(n=36)
|
Initial GT
(n=11)a
|
P-value
|
Age, years
|
40.1 ± 8.7
|
41.5 ± 9.4
|
0.68
|
Male sex, n (%)
|
29 (80.6)
|
10 (90.9)
|
0.73
|
Onset age, years
|
29.5 (22.0, 35.3)
|
24 (20.0, 29.5)
|
0.20
|
Duration of CH disease, years
|
8.5 (5.0, 12.5)
|
10 (8.0, 21.5)
|
0.07
|
Average duration of cluster period, weeks
|
6 (5.0, 8.0)
|
8 (4.5, 10.0)
|
0.67
|
time to GT from the onset of cluster bout, days
|
19 (13.2, 28.2)
|
9.0 (8.5, 23.5)
|
0.23
|
BMI, kg/m2
|
24.3 ± 4.3
|
23.5 ± 1.9
|
0.41
|
Ever-smoker
|
22 (61.1)
|
7 (63.6)
|
1.00
|
Current alcohol drinking
|
19 (52.7)
|
7 (63.9)
|
1.00
|
Comorbid migraine, n (%)
|
11 (30.4)
|
2 (18.2)
|
0.68
|
Abortive treatment
|
|
|
|
Oxygen, n (%)
|
10 (27.8)
|
3 (27.2)
|
1.00
|
Triptan, n (%)
|
29 (80.6)
|
4 (36.4)
|
0.26
|
CPT
|
|
|
|
Verapamil, n (%)
|
27 (75.0)
|
-
|
|
Lithium, n (%)
|
6 (16.7)
|
-
|
|
Prednisolone, n (%)
|
26 (72.2)
|
-
|
|
Occipital nerve block, n (%)
|
23 (63.9)
|
-
|
|
Topiramate, n (%)
|
14 (38.9)
|
-
|
|
Data is present as mean (standard deviation) or median (quartile) according to normality of variable. GT galcanezumab therapy, CPT conventional preventive therapy, CH cluster headache, BMI body mass index. a. Five patients added other conventional preventive therapies after the start of GT. |
Galcanezumab of 240 mg was injected an average of 18 days after the onset of current bout (range 1–62 days). Among the 12 patients who had ongoing attacks 1 month after GT, 4 patients received the second galcanezumab dose of 120 or 240 mg an average of 31 days after initial GT.
Occurrence of 100% and 50% reduction in CH attacks and days with acute medications after 240 mg of GT among ECH
Median time to the first occurrence of 100% reduction from baseline in CH attacks per week after the first GT was 17 days (25–75% quartile range: 5.0 ~ 29.5) in 47 patients with ECH. 100% reduction in CH attacks per week were achieved within 1 week in 13 patients (27.7%), within 2 weeks in additional 10 patients (21.3%), within 3 weeks in 6 more patients (12.8%). Finally, 35 patients got remission 1 month after GT.
Regarding the timing of GT, median time to first occurrence of 100% reduction from baseline in CH attacks per week was 15.5 days (3.8 ~ 22.1) in 36 patients with GT adding on CPT, 21.0 days (12.0 ~ 31.5) in 11 patients with initial GT, and 12.5 days (12.0 ~ 19.8) in 6 patients with GT as sole prevention. No recurrence was observed within 3 months after the occurrence of 100% reduction from baseline in CH attacks.
The efficacy of GT were analyzed about 50% reduction at week 3 from baseline of the numbers of CH attacks per week and the days with acute medications per week in 33 patients with headache diary data. The median number of weekly CH attacks and the median days with acute weekly medication significantly decreased from the baseline approximately three weeks after GT (Table 2). The proportion of patients with a 50% baseline reduction in weekly CH attacks at week 3 was 78.8% and the proportion in those taking acute weekly medication was 79.3%. The mean numbers of CH attacks were decreased from 8.6 attacks (SD 4.8) in baseline to 1.8 attacks (SD 2.4) in week 3.
Table 2
Efficacy of 240 mg of galcanezumab therapy at week 3 compared to baseline in patients with episodic cluster headache based on the headache diary (n = 33)
|
Baseline
|
Week 3
|
Patients with 50% response, n (%)
|
Patients with 100% response, n (%)
|
Number of attacks per week
|
7.0 (6.0, 10.0)
|
0 (0, 1.2) b
|
26 (78.8)
|
18 (54.5)
|
Days with acute medications per weeka
|
7.0 (3.0, 7.0)
|
0 (0, 1.2) b
|
23 (79.3)
|
18 (62.1)
|
Pain intensity during attacks [0–10]
|
8.0 (7.0, 9.0)
|
0 (0, 5.0) b
|
NA
|
NA
|
Data is present as mean (standard deviation) or median (quartile) according to normality of variable. a. 4 patients did not take any oral abortive medications during baseline. b. P-value of comparison from baseline to week 3; <0.001
Patient global impression of improvement and adverse response after galcanezumab therapy
Among 47 patients with ECH, PGI-I were reported as feeling “very much better” in 26 patients, “much better” in 12 patients, “a little better” in 7 patients, and “no change” in 2 patients. No patients reported feeling of any worse. The proportion of “very much better” or “much better” was 80.9% in 47 patients with ECH, 86.1% in 36 patients who received GT adding on CPT, 63.6% in 11 patients who received initial GT, and 66.7% in six patients who received GT as sole preventive therapy.
No serious AE occurred during the study period. More than half of the patients in both groups did not report any AE during GT (58.5% vs 72.7%, Table 3). There were no differences in the frequency of AE according to the timing of GT.
Table 3
Adverse events of 240 mg of galcanezumab therapy (GT) in patients with episodic cluster headache
|
GT adds on CPT
(n = 36)
|
Initial GT
(n = 11)a
|
None
|
21 (58.3)
|
8 (72.7)
|
Constipation
|
11 (29.5)
|
2 (16.7)
|
Hiccup
|
1 (2.7)
|
0
|
Myalgia
|
0
|
1 (8.3)
|
Neck pain
|
1 (2.7)
|
0
|
Injection-site swelling
|
2 (5.4)
|
0
|
Nocturia
|
1 (2.7)
|
0
|
GT galcanezumab therapy, CPT conventional preventive therapy. There was no significant difference between two groups, including the comparison about constipation (P = 0.48). a. Five patients added other conventional preventive therapies after the start of GT. |
Experience of galcanezumab therapy in 2 patients with chronic CH and 1 patient with first cluster bout
A 24-year-old male patient with primary chronic CH, enrolled 6 years after the onset of cluster bout and remitted after 2 months of consecutive GT. A 19-year-old male with secondary chronic CH enrolled 7 months after the onset of the cluster period and remitted 3 months after consecutive GT. A 29-year-old male in the first episode of cluster bout enrolled 2 months after the onset of cluster headache and remitted 24 days after GT. The patients had several conventional preventive therapies added onto the GT and none of them had a history of migraine. PGI-I were reported as feeling “very much better” in a patient primary secondary chronic CH and “much better” in a patient secondary chronic CH and a patient with the first episode of cluster bout.
Safety of GT with/without conventional preventive therapy in patients with CH
There were no deaths nor any serious AE during the study period. Nineteen patients reported diverse AEs. Constipation was the most common AEs (14 persons) among the patients in the GT group with/without conventional prevention therapy. Nocturia, myalgia, neck pain, diarrhea, hiccup, skin rash, skin excoriation, and heating sense were the other AEs reported during the study.