Emgality® (Galcanezumab)

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Galcanezumab: Injection-Site Reactions

Injection-site-related AEs were the most frequently reported AEs in the phase 3 studies. Most events were mild to moderate and did not lead to discontinuation.

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Additional Information

The information contained in this letter may not completely match the current local labeling for GALCANEZUMAB. Please see local labeling approved in your country. 

Galcanezumab has been studied in migraine prevention and cluster headache.1-8 Injection-site-related AEs for each population are summarized separately below.

Description of Migraine Analysis Set

Injection-site-related AEs were evaluated in phase 3 galcanezumab studies including

  • 2 randomized, double-blind, placebo-controlled, 6-month episodic migraine prevention studies (EVOLVE-1 and EVOLVE-2)1,2
  • 1 randomized, double-blind, placebo-controlled, 3-month chronic migraine prevention study with an optional 9-month open-label extension phase (REGAIN)3
  • 1 randomized, double-blind, placebo-controlled, 3-month migraine prevention study with an optional 3-month open-label extension phase in patients with episodic or chronic migraine who had not benefited from multiple previous migraine preventive treatments (CONQUER), and7,9
  • a 12-month, open-label safety study in patients with episodic or chronic migraine (CGAJ).6

In addition, injection-site-related AEs from a phase 2, double-blind, placebo-controlled, 6-month study in Japanese patients with episodic migraine (study CGAN) are also summarized.8

The long-term analysis set discussed below includes galcanezumab-treated patients from the

  • double-blind and open-label extension phase of REGAIN (month 0-12), and
  • 12-month open-label safety study, CGAJ.10

There were differences in the device and who administered the injections between EVOLVE-1, EVOLVE-2, REGAIN, CONQUER, study CGAJ, and study CGAN as shown in Device and Injection Administration in Galcanezumab Migraine Prevention Studies.

Device and Injection Administration in Galcanezumab Migraine Prevention Studies

In study...

Patients received...

SQ injectionsa were administered...

With a volume of...

By...

Using the following device...

EVOLVE-1, EVOLVE-2, REGAIN1-3,11

2 SQ injectionsb

monthly

1 mLc

investigative site personnel

prefilled syringe

CGAJ6,12

1 or 2 SQ injectionsd

monthly

1 mLc

self-administratione

prefilled syringe or autoinjectorf

CONQUER3,7

1 or 2 SQ injectionsg

monthly

1 mLc

investigative site personnel

prefilled syringe

CGAN8,11

1 or 2 SQ injectionsb

monthly

1 mLc

investigative site personnel

prefilled syringe

Abbreviation: SQ = subcutaneous.

aPossible injection-sites included the abdomen, thigh, upper arm, or buttocks.

bEVOLVE-1, EVOLVE-2, REGAIN, and CGAN: patients received 2 injections of 1 mL each via SQ injection at each visit. Patients received either galcanezumab 120 mg (2 injections of galcanezumab 120 mg as loading dose at first dosing visit, followed by 1 injection each of galcanezumab 120 mg and placebo at all subsequent dosing visits), galcanezumab 240 mg (2 injections of galcanezumab 120 mg), or placebo (2 placebo injections).

cEach injection was 1 mL.

dCGAJ: Patients randomized to the galcanezumab 120-mg dose received an initial loading dose of 240 mg (2 SQ injections of 120 mg each; 1 mL each) and 1 injection of 120 mg at each subsequent dosing visit. Patients randomized to the galcanezumab 240-mg dose received 2 SQ injections of 120 mg at each dosing visit.

eInvestigative site personnel administered the first injection. Self/caregiver administration started at the second injection visit after the loading dose administration by site staff and review of instructions for use for self-administration.

fPatients were switched from the prefilled syringe device to the autoinjector device. The device switch started after all patients had completed at least month 9 of the study, and 179 patients in study CGAJ received ≥1 galcanezumab dose using the autoinjector. Patients had up to 3-months exposure with the autoinjector.

gCONQUER: At the beginning of double-blind treatment, patients received either galcanezumab 120 mg (2 injections of galcanezumab 120 mg as loading dose at first dosing visit, followed by 1 injection of galcanezumab 120 mg at all subsequent dosing visits), or placebo (2 placebo injections at the first dosing visit, followed by 1 injection of placebo at subsequent dosing visits). At the beginning of open-label treatment, all patients received 2 injections to allow for blinded 240-mg loading dose of galcanezumab at month 3. Specifically, patients randomized to placebo during double-blind treatment received a loading dose of galcanezumab 240 mg, and patients randomized to galcanezumab during double-blind treatment received 1 injection of galcanezumab 120 mg and 1 injection of placebo.

Migraine Prevention: Injection-Site-Related Adverse Events

Migraine Prevention: Incidence of Injection-Site-Related Adverse Events

Injection-site-related AEs occurred in significantly more galcanezumab-treated patients than placebo in

In the CONQUER study, injection-site-related AEs occurred more frequently in placebo-treated patients (10%) than galcanezumab-treated patients (6.9%) during the double-blind treatment phase (Summary of Injection-Site-Related AEs: CONQUER Study).7

Injection-site-related AEs were reported by 21.8% of galcanezumab-treated patients in the long-term analysis set (REGAIN and CGAJ).10

Most Commonly Reported Injection-Site-Related Adverse Events

The most commonly reported injection-site-related AE was

  • injection-site pain in EVOLVE-1, EVOLVE-2, and REGAIN (10.9% galcanezumab pooled, 9.5% placebo), and the long-term analysis set (8.1% galcanezumab pooled),10 and
  • injection-site erythema in CONQUER (3.5% galcanezumab 120 mg, 2.6% placebo) and CGAN (21.0% galcanezumab pooled, 2.2% placebo).11

Migraine Prevention: Serious Adverse Events and Discontinuations

No SAEs related to injection-sites were reported in any of the studies (EVOLVE-1, EVOLVE-2, REGAIN, CONQUER, CGAJ, or CGAN).6,10,11,13,14 

Discontinuation due to an injection-site-related AE during double-blind, placebo-controlled treatment occurred at an incidence of <0.5% in the EVOLVE-1, EVOLVE-2, and REGAIN studies, and only in galcanezumab-treated patients,10,13 and <1% in the long-term analysis.10

In the EVOLVE-1, EVOLVE-2, and REGAIN studies, injection-site-related AEs resulting in study discontinuation were

  • moderate unspecified injection-site reaction (n=4)
  • moderate injection-site pain (n=1)
  • severe injection-site erythema (n=1), and
  • moderate injection-site swelling (n=1).10

All discontinuations due to injection-site-related AEs resolved without sequelae.11

During the CONQUER study, there were no discontinuations due to an injection-site-related AE during double-blind treatment and 1 patient discontinued due to injection-site erythema during open-label treatment.11,14

In the long-term analysis set, 9 patients discontinued due to injection-site-related AEs during open-label treatment. All discontinuations were observed following multiple doses of galcanezumab.10

In the CGAN study, 2 galcanezumab-treated patients (240 mg) reported severe injection-site reactions, but only 1 patient discontinued as a result. These were

  • injection-site erythema and injection-site pruritus (discontinued due to the injection-site erythema), and
  • injection-site pruritus, injection-site erythema, and injection-site induration (did not discontinue).8

Migraine Prevention: Characterization of Injection-Site-Related Adverse Events

The majority of patients reporting injection-site-related AEs (excluding pain) had events that

  • were mild to moderate in severity
  • occurred on the day of treatment administration, and
  • resolved, either on the same day or a few days afterward.6,8,10,11,13,14

In EVOLVE-1, EVOLVE-2, and REGAIN, all the 67 galcanezumab-treated patients who reported a nonspecified AE of injection-site reaction had at least 1 follow-up form completed to further characterize the unspecified injection-site reaction: Characterization of Nonspecific Injection-Site Reactions Reported by Galcanezumab-Treated Patients During Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN.10

Characterization of Nonspecific Injection-Site Reactionsa Reported by Galcanezumab-Treated Patients During Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN10,11

GMB 120 mg
n=22

GMB 240 mg
n=45

Pain

81%

71%

Itching

59%

60%

Rash or redness

59%

84%

Hardening of the injection site

59%

44%

Abbreviation: GMB = galcanezumab.

aA nonspecified adverse event of injection-site reaction: some sites recorded the adverse event of “injection site reaction” without further qualification while others were more specific in recording the symptom the patient reported at the site of the injection.

In CONQUER, each injection-site reaction was characterized based on a series of follow-up questions. Overall, 12.5% of galcanezumab-treated patients reported an injection-site reaction which was assessed using the injection-site reaction follow-up form: Characterization of Injection-Site Reactions Reported by Galcanezumab-Treated Patients in the CONQUER Study.14 More details were collected on the follow-up questions in the CONQUER study compared to the EVOLVE-1, EVOLVE-2, and REGAIN studies.

Characterization of Injection-Site Reactions Reported by Galcanezumab-Treated Patients in the CONQUER Study14

Injection-Site Reaction

GMB-Treated Timea
N=457
n (%)

Patients with >1 record of ISR follow-up form

57 (12.47)

Pain

Mild

27 (5.9)

Moderate

8 (1.8)

Severe

2 (0.4)

Erythema

Very mild

20 (4.4)

Clearly red

17 (3.7)

Bright red

3 (0.7)

Pruritus

Mild

15 (3.3)

Moderate

3 (0.7)

Severe

1 (0.2)

Induration

Barely noticeable

10 (2.2)

Slight

3 (0.7)

Moderate

5 (1.1)

Severe

3 (0.7)

Edema

Mild

7 (1.5)

Moderate

5 (1.1)

Severe

5 (1.1)

Abbreviation: GMB = galcanezumab; ISR = injection-site reaction.

aPatients were treated for up to 6 months with GMB (3 months double-blind/3 months open-label) or up to 3 months GMB (3 months placebo in double-blind/3 months GMB in open-label).

In the CONQUER study, most patients received either 3 or 6 monthly injections over the course of 6 months, and the reporting of injection-site reactions did not increase with the number of doses.14

In the long-term analysis set, the reporting of injection-site reactions (excluding pain) by galcanezumab-treated patients did not increase with multiple dose administrations. Overall, 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.10

An animation of the top 4 injection-site reactions and severity reported by galcanezumab-treated patients in study CGAJ, the 12-month open-label safety study, over time is available here.11 Please note that this animation depicts injection-site reactions over time from study CGAJ and is not representative of injection-site reaction rates in all galcanezumab migraine prevention studies.

Migraine Prevention: Injection-Site Reactions by Antidrug Antibody Status

A post hoc analysis of EVOLVE-1, EVOLVE-2, REGAIN, and CGAJ studies reported no evidence that injection-site-related AEs were mediated by TE ADA in galcanezumab-treated patients. No specific injection-site-related AEs were reported exclusively in TE ADA+ patients.10,15

In TE ADA+ patients who reported injection-site-related AEs (Injection-Site-Related AEs and ADA in Galcanezumab-Treated Patients: Cases That Met Flagging for Further Review in Phase 3 Migraine Prevention Studies)

  • 1 patient reported injection-site inflammation before the development of TE ADA which did not recur after the detection of titer increase of antibodies, and
  • 2 patients had already detectable TE ADA before reporting injection-site rash.15
Injection-Site-Related AEs and ADA in Galcanezumab-Treated Patients: Cases That Met Flagging for Further Reviewa in Phase 3 Migraine Prevention Studies15

Preferred Term

TE ADA Status

N

n (%)

Injection site rash

Yes

92

2 (2.2%)

No

1562

10 (0.6%)

Injection site inflammation

Yes

92

1 (1.1%)

No

1562

1 (0.1%)

Abbreviations: ADA = antidrug antibodies; AE = adverse event; N = number of patients in the analysis population; n = number of patients within each specific category; TE ADA = treatment-emergent anti-drug antibody.

aCriteria for case level review were based on odds ratio and p value from the Cochran-Mantel-Haenszel test that compared the proportions of patients with ≥1 preferred term related to injection-sites between TE ADA+ and TE ADA- patients, stratified by study. Events with an odds ratio >2.0 or p≤.05 met flagging criteria for further review.

Description of Cluster Headache Analysis Set

Injection-site-related AEs were evaluated in phase 3 randomized, double-blind, placebo-controlled galcanezumab studies including a

  • 2-month episodic cluster headache study (CGAL),4 and
  • 3-month chronic cluster headache study with an optional 12-month open-label extension for completers of the double-blind period (CGAM).5

The CGAM study in chronic cluster headache did not meet its primary endpoint.5 However, safety results from the 2 placebo-controlled cluster headache trials were integrated and are the primary analysis set used for evaluation of galcanezumab safety in cluster headache.11

A summary of dosing and administration in the phase 3 cluster headache studies is summarized below: Device and Injection Administration in Phase 3 Galcanezumab Cluster Headache Studies.

Device and Injection Administration in Phase 3 Galcanezumab Cluster Headache Studies

In study...

Patients received...

SQ injectionsa were administered...

With a volume of...

By...

Using the following device...

CGAL, CGAM4,5,11

3 SQ injectionsb

monthly

1 mLc

investigative site personnel

syringed

Abbreviation: SQ = subcutaneous.

aPossible injection-sites included the abdomen, thigh, upper arm, or buttocks.

bPatients received either galcanezumab 300 mg (3 injections of galcanezumab 100 mg) or placebo (3 placebo injections).

cEach injection was 1 mL.

dDuring the open-label portion of study CGAM, a prefilled syringe with a solution formulation was made available.

Cluster Headache: Injection-Site-Related Adverse Events

Cluster Headache: Incidence of Injection-Site-Related Adverse Events

Injection-site-related AEs occurred in significantly more galcanezumab-treated patients than placebo: Summary of Injection-Site-Related AEs During Phase 3 Double-Blind Treatment: Cluster Headache.11

Summary of Injection-Site-Related AEs During Phase 3 Double-Blind Treatment: Cluster Headache4,5,11
Eventab
PBO
N=177
n (%)
GMB 300 mg
N=166
n (%)

Patients with ≥1 TEAE

14 (7.9)

36 (21.7)c

Patients with ≥1 TEAE, excluding injection site pain

5 (2.8)

23 (13.9)c

Injection site pain

11 (6.2)

17 (10.2)

Injection site erythema

1 (0.6)

9 (5.4)d

Injection site pruritus

2 (1.1)

5 (3.0)

Injection site swelling

1 (0.6)

3 (1.8)

Injection site bruising

0 (0.0)

2 (1.2)

Injection site induration

0 (0.0)

2 (1.2)

Injection site discoloration

1 (0.6)

1 (0.6)

Injection site hypersensitivity

0 (0.0)

1 (0.6)

Injection site edema

0 (0.0)

1 (0.6)

Injection site rash

0 (0.0)

1 (0.6)

Injection site reaction

0 (0.0)

1 (0.6)

Injection site urticaria

0 (0.0)

1 (0.6)

Injection site hematoma

1 (0.6)

0 (0.0)

Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TEAE = treatment-emergent adverse event.

aPreferred term.

bAll AEs listed in the MedDRA version 20.1 high-level term of "injection site reactions" were analyzed.

cp<.001 vs PBO.

dp=.009 vs PBO.

Cluster Headache: Serious Adverse Events and Discontinuations

There were no injection-site-related SAEs or discontinuations due to injection-site-related AEs in the phase 3 cluster headache double-blind studies.4,5,11

Cluster Headache: Characterization of Injection-Site-Related Adverse Events

In the phase 3 studies the majority of patients reporting injection-site-related AEs had events that

  • were generally mild to moderate in severity
  • occurred on the day of treatment administration, and
  • resolved, on average, in less than 5 days.11

Adverse event follow-up forms were used to characterize the reported nonspecified event of injection-site reaction (meaning that the AE of "injection site reaction" was recorded by the clinical trial site without further qualification). Only 1 patient in the galcanezumab treatment group reported 2 events of injection-site reaction that had a follow-up form for each event. Both events of injection-site reaction reported by this patient

  • occurred within 60 minutes of administration
  • occurred in the arm, and
  • were associated with hardening (including lump or knot) of ≥1 cm.11

Cluster Headache: Summary

The injection-site-related AEs in the phase 3 placebo-controlled trials were consistent with the known safety profile of galcanezumab and showed that longer treatment duration did not result in increased frequency of injection-site-related TEAEs.11

Postmarketing Spontaneous Reports

Through March 27, 2020, MedDRA terms related to injection-site reactions that have been reported in the Eli Lilly and Company spontaneous AE database are provided in Galcanezumab Postmarketing Reporting Rates of Injection-Site Reactions Through 27 March 2020.11

Galcanezumab Postmarketing Reporting Rates of Injection-Site Reactionsa Through 27 March 202011

Uncommonly Reported (≥0.1% and <1%)

Rarely Reported (≥0.01% and <0.1%)

Very Rarely Reported (<0.01%)

injection site erythema, injection site pain, injection site pruritus, injection site reaction, injection site swelling

injection site bruising, injection site discomfort, injection site hemorrhage, injection site hypersensitivity, injection site induration, injection site injury, injection site irritation, injection site mass, injection site rash, injection site urticaria, injection site warmth

injection site cellulitis, injection site coldness, injection site discoloration, injection site dryness, injection site exfoliation, injection site extravasation, injection site hematoma, injection site hyperesthesia, injection site hypoesthesia, injection site infection, injection site joint erythema, injection site inflammation, injection site laceration, injection site macule, injection site nodule, injection site edema, injection site pallor, injection site papule, injection site paresthesia, injection site plaque, injection site pustule, injection site scab, injection site scar, injection site vesicles

Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities.

aMedDRA preferred terms.

Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an event.16

Spontaneous reporting has limited use due to

  • lack of control population
  • under-reporting or reporting bias, and
  • missing or incomplete information regarding medical history or concomitant medications.16

Prevention and Management of Injection-Site-Related Adverse Events

Safe practices for administering SQ injections include

  • leaving the medication to sit at room temperature for 30 minutes prior to injection
  • washing hands
  • cleaning and drying the site prior to injection
  • rotation of injection-sites
  • not injecting into areas where the skin is tender, bruised, red, or hard, and 
  • not massaging or rubbing the site after injection.11,17,18

Comfort Measures

In the CONQUER study, staff were encouraged to administer comfort measures, such as cold compress, ice pack, or topical anesthetic cream, to the injection-site prior to or after the injection at their clinical discretion as needed.14  

The percentage of patients who used comfort measures around the time of injection was low and similar between treatment groups during double-blind treatment: Comfort Measures Used at Injection-Sites During Double-Blind Treatment: CONQUER. The most frequently used comfort measure was application of an ice pack.11

Comfort Measures Used at Injection-Sites During Double-Blind Treatment: CONQUER11,14

 

PBO
M=916
n (%)

GMB 120 mg
M=918
n (%)

Comfort measures used before injection

12 (1.3)

15 (1.6)

Ice pack

10 (1.1)

15 (1.6)

Cold compress

2 (0.2)

0 (0.0)

Topical anesthetic or analgesic cream

0 (0.0)

0 (0.0)

Comfort measures used after injection

23 (2.5)

29 (3.2)

Ice pack

19 (2.1)

27 (2.9)

Cold compress

4 (0.4)

2 (0.2)

Topical anesthetic or analgesic cream

0 (0.0)

0 (0.0)

Abbreviations: GMB = galcanezumab; M = number of injections used for the analysis population; PBO = placebo.

Although management of injection-site-related AEs was not outlined in the phase 3 study protocols (EVOLVE-1, EVOLVE-2, REGAIN, CGAJ for migraine prevention or CGAL and CGAM for cluster headache), premedication was not prohibited.11

Concomitant medications including acetaminophen (paracetamol) and NSAIDs were permitted. Other concomitant medications such as topical steroids and topical or oral antihistamines were not prohibited. The use of oral steroids was prohibited.11

Management of injection-site-related AEs in the EVOLVE-1, EVOLVE-2, REGAIN, CGAJ, CGAL, and CGAM studies was at the discretion of the study investigators.11 The decision whether to premedicate a patient prior to galcanezumab injection should be made at the discretion of the prescribing physician.

Factors for Injection-Site Pain and Adverse Events

Injection-site pain and AEs following SQ injection might vary depending on patient-related factors, properties of the compound, and the cellular dynamics at the site of injection.10,19 Examples include

  • injection speed (injection-site pain with fast injections)
  • patient differences in pain tolerance
  • formulation temperature (should ideally be close to body temperature)
  • type of injectable device (prefilled syringe or autoinjector)
  • injection volume (ideally should be ≤3 mL)
  • physiologic pH, and
  • excipients.10

As noted in Summary of Injection-Site-Related AEs During Phase 3 Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN, a similar incidence of injection-site pain was observed during short-term exposure between placebo- and galcanezumab-treated patients. This may explain the possibility that formulation-based factors could have resulted in injection-site pain, including

  • a nonphysiological pH of less than 7 (galcanezumab pH is 5.3-6.3), and
  • the presence of polysorbate 80.10

Other inactive excipients in the galcanezumab formulation include L-histidine, histidine hydrochloride monohydrate, and sodium chloride.10

Referencias

1Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543

2Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212

3Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640

4Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381(2):132-141. http://dx.doi.org/10.1056/NEJMoa1813440

5Dodick DW, Goadsby PJ, Lucas C, et al. Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: results from 3-month double-blind treatment. Cephalalgia. 2020;40(9):935-948. http://dx.doi.org/10.1177/0333102420905321

6Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

7Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. http://dx.doi.org/10.1016/S1474-4422(20)30279-9

8Sakai F, Ozeki A, Skljarevski V. Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: a phase 2 randomized controlled clinical trial. Cephalalgia Rep. 2020;3:251581632093257. http://dx.doi.org/10.1177/2515816320932573

9Detke HC, Reuter U, Lucas C, et al. Galcanezumab in patients with treatment-resistant migraine: results from the open-label phase of the CONQUER phase 3 trial. Poster presented at: 14th European Headache Federation (EHF Virtual); June 29-July 2, 2020.

10Stauffer VL, Wang S, Bonner J, et al. Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of phase 3 studies in participants with migraine. BMC Neurol. 2020;20(1):194. https://doi.org/10.1186/s12883-020-01775-4

11Data on file, Eli Lilly and Company and/or one of its subsidiaries.

12Stauffer VL, Sides R, Lanteri-Minet M, et al. Comparison between prefilled syringe and autoinjector devices on patient-reported experiences and pharmacokinetics in galcanezumab studies. Patient Prefer Adherence. 2018;12:1785-1795. http://dx.doi.org/10.2147/ppa.s170636

13Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020;20(1):25. https://doi.org/10.1186/s12883-020-1609-7

14Stauffer VL, Lanteri-Minet M, García-Azorín D, et al. Characterization of injection-site reactions from the CONQUER study of galcanezumab in patients with treatment-resistant migraine. Cephalalgia. 2020;40(suppl 1):18-110. Migraine Trust Virtual 2020 - Digital Symposium abstract MTV20-DP-053. https://doi.org/10.1177/0333102420962305

15Martinez JM, Hindiyeh N, Anglin G, et al. Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine. Cephalalgia. 2020;40(9):978-989. https://doi.org/10.1177/0333102420920642

16Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-C44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6

17Ogston-Tuck S. Subcutaneous injection technique: an evidence-based approach. Nurs Stand. 2014;29(3):53-58. http://dx.doi.org/10.7748/ns.29.3.53.e9183

18Emgality [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.

19Workman B. Safe injection techniques. Nurs Stand. 1999;13(39):47-53. https://doi.org/10.7748/ns1999.06.13.39.47.c2623

Glossary

AE = adverse event

MedDRA = Medical Dictionary for Regulatory Activities

NSAID = nonsteroidal anti-inflammatory drug

SAE = serious adverse event

SQ = subcutaneous

TE ADA = treatment-emergent anti-drug antibodies

TEAE = treatment-emergent adverse event

Appendix

Migraine Prevention: Summary of Injection-Site-Related Adverse Events

Summary of Injection-Site-Related AEs During Phase 3 Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAINa10,11

Eventbc

PBO
N=1451
n (%)

GMB 120 mg
N=705
n (%)

GMB 240 mg
N=730
n (%)

GMB Pooled
N=1435
n (%)

Patients with ≥1 TEAE

183 (12.6)

128 (18.2)d

166 (22.7)de

294 (20.5)d

Patients with ≥1 TEAE, excluding injection site painf

60 (4.1)

70 (9.9)d

106 (14.5)dg

176 (12.3)d

Injection site pain

138 (9.5)

71 (10.1)

85 (11.6)

156 (10.9)

Unspecified injection site reaction

14 (1.0)

22 (3.1)d

45 (6.2)dh

67 (4.7)d

Injection site erythema

20 (1.4)

20 (2.8)i

29 (4.0)d

49 (3.4)d

Injection site pruritus

2 (0.1)

15 (2.1)d

24 (3.3)d

39 (2.7)d

Injection site bruising

9 (0.6)

4 (0.6)

10 (1.4)

14 (1.0)

Injection site swelling

1 (0.1)

8 (1.1)d

4 (0.6)j

12 (0.8)k

Injection site rash

2 (0.1)

6 (0.9)l

4 (0.6)

10 (0.7)m

Injection site induration

1 (0.1)

3 (0.4)

3 (0.4)

6 (0.4)

Injection site discomfort

3 (0.2)

3 (0.4)

2 (0.3)

5 (0.4)

Injection site hematoma

7 (0.5)

1 (0.1)

3 (0.4)

4 (0.3)

Injection site hypersensitivity

0 (0.0)

1 (0.1)

3 (0.4)n

4 (0.3)o

Injection site mass

0 (0.0)

3 (0.4)p

0 (0.0)

3 (0.2)

Injection site hemorrhage

2 (0.1)

1 (0.1)

1 (0.1)

2 (0.1)

Injection site inflammation

0 (0.0)

1 (0.1)

1 (0.1)

2 (0.1)

Injection site irritation

3 (0.2)

1 (0.1)

1 (0.1)

2 (0.1)

Injection site urticaria

1 (0.1)

1 (0.1)

1 (0.1)

2 (0.1)

Injection site discoloration

0 (0.0)

0 (0.0)

1 (0.1)

1 (0.1)

Injection site edema

1 (0.1)

1 (0.1)

0 (0.0)

1 (0.1)

Injection site papule

0 (0.0)

1 (0.1)

0 (0.0)

1 (0.1)

Injection site vesicles

0 (0.0)

0 (0.0)

1 (0.1)

1 (0.1)

Injection site warmth

1 (0.1)

0 (0.0)

0 (0.0)

0 (0.0)

Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TEAE = treatment-emergent adverse event.

aPrefilled syringe was used in these trials.

bPreferred term.

cAll AEs listed in the MedDRA version 19.1 high-level term of "injection site reactions" were analyzed.

dp<.001 vs PBO.

ep=.033 vs GMB 120 mg.

fMost frequently reported terms (not less than 1.5% of all preferred terms which included: injection site reaction, injection site erythema, and injection site pruritus).

gp=.008 vs GMB 120 mg.

hp=.006 vs GMB 120 mg.

ip=.017 vs PBO.

jp=.028 vs PBO.

kp=.002 vs PBO.

lp=.011 vs PBO.

mp=.02 vs PBO.

np=.015 vs PBO.

op=.044 vs PBO.

pp=.012 vs PBO.

Summary of Injection-Site-Related AEs: CONQUER Studya7,9,11

 

PBO
N=230
n (%)

GMB 120 mg
N=232
n (%)

GMB 120 mg
N=457
n (%)

Eventbc

Double-Blind Treatment Phase

Open-Label Treatment Phased

Patients with ≥1 TEAE

23.0 (10.0)

16 (6.9)

50 (10.9)

Injection site erythema

6 (2.6)

8 (3.5)

19 (4.2)

Injection site pain

13 (5.7)

5 (2.2)

20 (4.4)

Injection site pruritus

0 (0.0)

3 (1.3)

9 (2.0)

Injection site edema

0 (0.0)

2 (0.9)

3 (0.7)

Injection site discoloration

1 (0.4)

1 (0.4)

3 (0.7)

Injection site hypersensitivity

0 (0.0)

1 (0.4)

1 (0.2)

Injection site induration

4 (1.7)

1 (0.4)

5 (1.1)

Injection site paresthesia

3 (1.3)

1 (0.4)

3 (0.7)

Injection site swelling

0 (0.0)

1 (0.4)

2 (0.4)

Injection site bruising

4 (1.7)

0 (0.0)

2 (0.4)

Injection site hematoma

1 (0.4)

0 (0.0)

1 (0.2)

Injection site reaction

6 (2.6)e

0 (0.0)

8 (1.8)

Injection site inflammation

NR

NR

1 (0.2)

Injection site irritation

NR

NR

1 (0.2)

Injection site rash

NR

NR

1 (0.2)

Injection site vesicles

NR

NR

1 (0.2)

Injection site warmth

NR

NR

1 (0.2)

Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; NR = not reported; PBO = placebo; TEAE = treatment-emergent adverse event.

aPrefilled syringe was used in this study.

bPreferred term.

cAdverse events related to injection-sites were defined using terms from the MedDRA version 22.0 high level-term of "Injection site reactions".

dGalcanezumab-treated population: patients who received up to 6 months of GMB treatment in addition to patients on PBO in the double-blind treatment phase who received GMB during open-label treatment.

ep=.015 vs GMB 120 mg.

Summary of Injection-Site-Related AEs: Phase 2 Studya in Japanese Patients With Episodic Migraine8,11

Eventbc

PBO
N=230
n (%)

GMB 120 mg
N=115
n (%)

GMB 240 mg
N=114
n (%)

GMB Pooled
N=229
n (%)

Patients with ≥1 TEAE

13 (5.7)

30 (26.1)d

45 (39.5)de

75 (32.8)d

Patients with ≥1 TEAE, excluding injection site pain

12 (5.2)

27 (23.5)d

43 (37.7)df

70 (30.6)d

Injection site erythema

5 (2.2)

17 (14.8)d

31 (27.2)dg

48 (21.0)d

Injection site pruritus

0 (0.0)

10 (8.7)d

23 (20.2)dh

33 (14.4)d

Injection site swelling

3 (1.3)

12 (10.4)d

12 (10.5)d

24 (10.5)d

Injection site pain

3 (1.3)

7 (6.1)i

8 (7.0)j

15 (6.6)k

Injection site induration

1 (0.4)

3 (2.6)

3 (2.6)

6 (2.6)

Injection site inflammation

0 (0.0)

3 (2.6)l

0 (0.0)

3 (1.3)

Injection site rash

2 (0.9)

0 (0.0)

3 (2.6)

3 (1.3)

Injection site warmth

0 (0.0)

2 (1.7)

1 (0.9)

3 (1.3)

Injection site bruising

4 (1.7)

2 (1.7)

0 (0.0)

2 (0.9)

Injection site mass

0 (0.0)

1 (0.9)

1 (0.9)

2 (0.9)

Injection site urticaria

0 (0.0)

1 (0.9)

1 (0.9)

2 (0.9)

Injection site dermatitis

0 (0.0)

0 (0.0)

1 (0.9)

1 (0.4)

Injection site eczema

0 (0.0)

0 (0.0)

1 (0.9)

1 (0.4)

Injection site hemorrhage

1 (0.4)

1 (0.9)

0 (0.0)

1 (0.4)

Injection site discoloration

1 (0.4)

0 (0.0)

0 (0.0)

0 (0.0)

Injection site discomfort

1 (0.4)

0 (0.0)

0 (0.0)

0 (0.0)

Injection site reaction

1 (0.4)

0 (0.0)

0 (0.0)

0 (0.0)

Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TEAE = treatment-emergent adverse event.

aPrefilled syringe was used in this study.

bPreferred term.

cAdverse events related to injection-sites were defined using terms from the MedDRA version 21.1 high-level term of "Injection site reactions".

dp<.001 vs PBO.

ep=.035 vs GMB 120 mg.

fp=.022 vs GMB 120 mg.

gp=.024 vs GMB 120 mg.

hp=.015 vs GMB 120 mg.

ip=.018 vs PBO.

jp=.008 vs PBO.

kp=.004 vs PBO.

lp=.036 vs PBO.

Fecha de la última revisión: 2020 M11 12


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