All 3156 participants from the EVOLVE-1, EVOLVE-2 and REGAIN studies were included in this post hoc analysis (placebo, n=1451; galcanezumab 120 mg, n=840; galcanezumab 240 mg, n=865). In this integrated analysis set of EVOLVE-1, EVOLVE-2 and REGAIN studies, participants were predominantly women (placebo, 1237/1451 [85.3%]; galcanezumab 120 mg, 599/705 [85.0%]; galcanezumab 240 mg, 609/730 [83.4%]), with a mean age of ~41 years (Table 1). On an average, participants were diagnosed as having migraine ~20 years prior to study enrolment. Baseline demographics of race, region and comorbid conditions were similar across treatment groups. The most common comorbid conditions (occurring in >10% of all participants), included seasonal allergy, drug hypersensitivity, insomnia, anxiety, depression, and back pain.
In Study CGAJ, participants were predominantly women (galcanezumab 120 mg, 110/135 [81.5%]; galcanezumab 240 mg 113/135 [83.7%]), with a mean age of ~42 years (mean [SD]: galcanezumab 120 mg, 40.2 [11.7]; galcanezumab 240 mg, 43.7 [11.0]) and a diagnosis of migraine of ~20 years prior to study enrolment (mean [SD]: galcanezumab 120 mg, 20.2 [12.4]; galcanezumab 240 mg, 21.3 [12.5]). The detailed demographics are published elsewhere .
Injection-site reactions during double-blind phase of EVOLVE-1, EVOLVE-2 and REGAIN studies
During the DB treatment phase of EVOLVE-1, EVOLVE-2 and REGAIN studies, 477 (477/2886, 16.5%) participants reported at least one injection-site reaction (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]). The injection-site reactions were significantly higher (P ≤ 0.001) with galcanezumab 240 mg or 120 mg compared with placebo (Table 2). The most commonly (≥2%) observed injection-site reactions were injection-site pain, unspecified injection site reaction, injection-site erythema, and injection-site pruritus. These were reported by higher proportion of participants in galcanezumab 240 mg and 120 mg groups compared with placebo (Table 2).
Of the 67 galcanezumab-treated participants who reported an unspecified injection site reaction (galcanezumab 120 mg, 22/705 [3.1%]; galcanezumab 240 mg, 45/730 [6.2%]), all participants completed at least one follow-up form which was used to further characterise the reported unspecified injection site reaction. Of these 67 participants, 59.1% (13/22) participants on galcanezumab 120 mg reported itching, rash or redness, and injection-site hardening. Itching, rash or redness, and injection-site hardening were reported by 60.0% (27/45), 84.4% (38/45), and 44.4% (20/45) participants on galcanezumab 240 mg, respectively.
Among patients who reported injection-site reactions, most reported injection-site reactions of mild-to-moderate severity. (Table 3). No injection-site reactions were reported as SAEs. Overall seven participants discontinued due to injection-site reactions (galcanezumab 120 mg, n=2; galcanezumab 240 mg, n=5). Among these participants, four participants discontinued due to moderate unspecified injection-site reaction (galcanezumab 120 mg, 1/705 [0.1%]; galcanezumab 240 mg, 3/730 [0.4%]). The remaining three patients discontinued due to moderate injection-site pain (galcanezumab 240 mg, 1/1451 [0.1%]), severe injection-site erythema (galcanezumab 120 mg, 1/705 [0.1%]), and moderate injection-site swelling (galcanezumab 240 mg, 1/730 [0.1%]) Table 3.
Injection-site pain was the most common immediate injection-site reaction reported within 60 minutes of injection) and was observed in approximately 86% of participants reporting injection-site pain (Table 4). Majority of unspecified-injection-site reaction (placebo, 100.0%; galcanezumab, 88.0%), injection-site erythema (placebo, 95.0%; galcanezumab, 79.0%) and injection-site pruritus (placebo, 100%; galcanezumab. 74.4%) occurred on the day of injection (Table 4). Only two participants on galcanezumab (galcanezumab 120 mg, 1 [1.4%] and galcanezumab 240 mg, 1 [1.2%]) had a reaction after 14 days. Majority of the injection-site reactions occurred on the day of injection and were resolved, either on the same day or a few days afterwards (mean [SD] duration in days, injection-site pain: placebo, 1.6 [8.35]; galcanezumab 120 mg, 1.2 [1.01]; galcanezumab 240 mg, 1.5 [2.68] and injection-site reaction excluding pain: placebo, 2.0 [8.76]; galcanezumab 120 mg, 2.8 [5.46]; galcanezumab 240 mg, 2.7 [4.17]).
Injection-site reactions during long-term treatment with galcanezumab in REGAIN and Study CGAJ
During the long-term exposure of galcanezumab, 289 (289/1326, 21.8%) participants reported AEs related to injection-sites. The most frequently reported injection-site reactions were injection-site pain (galcanezumab pooled, 108/1326 [8.1%]), unspecified injection-site reaction (galcanezumab pooled, 103/1326 [7.8%]), injection-site erythema (galcanezumab pooled, 62/1326 [4.7%]), and injection-site pruritus (galcanezumab pooled, 30/1326 [2.3%]; Table 5). Overall nine patients discontinued the treatment due to injection-site reactions (Study CGAJ, n=5; REGAIN, n=4). All discontinuations were observed following multiple doses of galcanezumab (fourth, n=1; fifth injection, n=1; sixth injection, n=1; seventh injection, n=3; ninth injection, n=1; 10th injection, n=2).
To evaluate if galcanezumab-treated patients reported multiple injection-site reactions (excluding pain) over consecutive monthly injections, the number of TEAEs related to injection-sites (excluding pain) by total number of doses is provided in Table 6. In summary 81% of patients received 9 doses or more of galcanezumab and most patients reported 1 to 3 events with monthly injections over 9 to 12 months suggesting that the reporting of injection-site reactions (excluding pain) did not increase with multiple dose administrations.