Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Smärta vid injektionsstället

Injektionsplatsrelaterade biverkningar var de vanligaste rapporterade biverkningarna i fas 3-studierna. De flesta händelser var milda till måttliga och ledde inte till avbrott

Information On Injection Site Related Events

Injection site pain and Injection site reactions are very common adverse reactions of galcanezumab.

  • Injection site pain was reported by 10.1 % and 11.6 % of patients with 120 mg and 240 mg galcanezumab, respectively.

  • Injection site reactions were reported by 9.9 % and 14.5 % of patients  with 120 mg and 240 mg galcanezumab, respectively.1

  • The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

With regard to Injection site reactions, the most frequently reported terms (≥ 1 %) were:

  • Injection site reaction

  • Injection site erythema

  • Injection site pruritus

  • Injection site bruising

  • Injection site swelling.1

The majority of events related to the injection site were mild to moderate and less than 0.5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction.1

The majority of injection site reactions were reported within 1 day and on average resolved within 5 days. In 86 % of the patients reporting injection site pain, the event occurred within 1 hour of injection and resolved on average in 1 day.1

One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.1

Description of 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)2,3

  • 1 randomized, double-blind, placebo-controlled, 3-month chronic migraine prevention study with an optional 9-month open-label extension phase (REGAIN),4 and

  • a 12-month, open-label safety study in patients with episodic or chronic migraine (CGAJ).5

The results below are focused primarily on the findings from EVOLVE-1, EVOLVE-2, and REGAIN.6

There were differences in the device and who administered the injections between EVOLVE-1, EVOLVE-2, REGAIN, and study CGAJ as shown inTable 1 .

Table 1. Device and Injection Administration in Phase 3 Galcanezumab Studies

In study...

Patients received...

SQ injectionsa were administered...

With a volume of...

By...

Using the following device...

EVOLVE-1, EVOLVE-2, REGAIN4,7-10

2 SQ injectionsb

monthly

1 mL

investigative site personnel

prefilled syringe

CGAJ5,11

1 or 2 SQ injectionsc

monthly

1 mL

self-administrationd

prefilled syringe or autoinjectore

Abbreviation: SQ = subcutaneous.

a Possible injection sites included the abdomen, thigh, arm, or buttocks.

b EVOLVE-1, EVOLVE-2, and REGAIN: 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).

c CGAJ: 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.

d Investigative 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.

e Patients 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.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .1 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Migraine Prevention: Treatment-emergent Reports of Injection Site Pain

Injection site pain was the most frequently reported TEAE in phase 3 migraine prevention clinical trials, with a similar incidence between patients treated with galcanezumab (10.9%) or placebo (9.5%).6 

The incidence of overall injection site-related AEs is summarized in: Table 2.

Table 2. Summary of Injection Site-related AEs During Phase 3 Double-blind Treatment: Migraine Prevention10

Eventab

PBO
N=1451
n (%)

GMB 120 mg
N=705
n (%)

GMB 240mg
N=730
n (%)

GMB Pooled
N=1435
n (%)

Patients with ≥1 TEAE

183 (12.6)

128 (8.2)c

166 (22.7)cd

294 (20.5)c

Patients with ≥1 TEAE, excluding injection site paine

60 (4.1)

70 (9.9)c

106 (14.5)cf

176 (12.3)c

Injection site pain

138 (9.5)

71 (10.1)

85 (11.6)

156 (10.9)

Abbreviations: AE = adverse event; GMB = galcanezumab; PBO = placebo; TEAE = treatment-emergent adverse event.

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

b Preferred term.

c p<.001 vs placebo.

d p=.033 vs GMB 120 mg.

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

f p=.008 vs GMB 120 mg.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .1 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Migraine Prevention: SAEs and Discontinuations

In the phase 3 double-blind studies, no events of injection site pain were reported as an SAE and 1 galcanezumab-treated patient discontinued due to injection site pain.10

Migraine Prevention: Characterization of Injection Site Pain

Reports of injection site pain in the phase 3 double-blind studies 

  • were reported as "injection site burning" in 50% of events

  • were mostly mild to moderate in severity

  • had an onset within 60 minutes of injection, and

  • resolved in 1.4 days on average.10

The percentage of patients reporting severe pain was comparable among all galcanezumab- and placebo-treated patients (1.1% and 1.2%, respectively). Note that the injection site pain severity assessment was subjective and did not include additional descriptors other than mild, moderate, and severe for severity.10

Migraine Prevention: Open-label Safety Study CGAJ

In the long-term safety study, CGAJ,

  • the frequency of injection site pain in galcanezumab-treated patients was 18.52% (120 mg, 17.1%; 240 mg, 19.9%)5, and

  • no patients discontinued due to injection site pain.9

Migraine Prevention: Exposure Adjusted Incidence Rate

EAIRs are a measure of whether TEAEs occur at an increased frequency with increased treatment duration.9

The injection site pain EAIR for the galcanezumab pooled group was lower for the long-term, open-label safety study CGAJ compared with EVOLVE-1, EVOLVE-2, and REGAIN (25.54 vs 32.50, respectively).9 EAIR is equal to 100 times the number of patients experiencing the event divided by event-specific total patient-year-at-risk.

Prevention and Management of Injection Site Pain

Although management of injection site-related AEs was not outlined in the phase 3 migraine prevention study protocols, premedication was not prohibited.9

Concomitant medications including acetaminophen (paracetamol) and NSAIDs were permitted. Other concomitant medications such a topical steroids and topical or oral antihistamines were not prohibited. The use of oral steroids was excluded.9

Management of injection site-related AEs in the studies was at the discretion of the study investigators.9 The decision whether to pre-medicate a patient prior to galcanezumab injection should be made at the discretion of the prescribing physician.

Injection site pain and AEs following SQ injection might vary depending on the properties of the compound and the cellular dynamics at the site of injection.12 Safe practices for administering SQ injections include

  • leaving the medication 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.13,14

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.1

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1

References

1. Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Stauffer 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

3. Skljarevski 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

4. Detke 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

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

6. Stauffer VL, Wang S, Bangs M, et al. Phase 3 safety data from studies comparing galcanezumab and placebo in patients with episodic and chronic migraine. Poster presented at: European Academy of Neurology (EAN) – 4th Congress; June 16-19, 2018; Lisbon, Portugal.

7. Stauffer 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

8. Skljarevski 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

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

10. Stauffer VL, Wang S, Carter JN, et al. Evaluation of injection site related adverse events from the phase 3 placebo controlled trials of galcanezumab for migraine prevention. Poster presented at: Migraine Trust International Symposium (MTIS) – 17th Biennial Meeting; September 6-9, 2018; London, United Kingdom.

11. Stauffer VL, Sides R, Kielbasa W, Jin Y. Patient-reported experiences with self-injections using prefilled syringe and autoinjector devices in an open-label, long-term study of galcanezumab in patients with migraine. Poster presented at: American Headache Society (AHS) – 60th Annual Meeting; June 28 – July 1, 2018; San Francisco, CA.

12. Workman B. Safe injection techniques. Nurs Stand. 1999;13(39):47-53. http://www.ncbi.nlm.nih.gov/pubmed/10497490

13. Ogston-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

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

Glossary

AE = adverse event

EAIR = exposure-adjusted incidence rate

NSAID = nonsteroidal anti-inflammatory drug

SAE = serious adverse event

SQ = subcutaneous

TEAE = treatment-emergent adverse event

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2018 M09 04

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