Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Påverkan på funktion

En större minskning av den totala smärtbördan sågs hos patienter med episodisk eller kronisk migrän som behandlades med galcanezumab 120 mg en gång i månaden, jämfört med placebo.

Overview of Migraine Prevention Phase 3 Program

Galcanezumab has been studied in phase 3, randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

  • episodic migraine (EVOLVE-1 and EVOLVE-2)1,2

  • chronic migraine (REGAIN),3 and

  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).4

Patients were randomized to either placebo or treatment in a

  • 2:1:1 ratio in the EVOLVE-1, EVOLVE-2, REGAIN studies,1-3 and

  • 1:1 ratio in the CONQUER study.4

The galcanezumab doses studied in 

  • EVOLVE-1, EVOLVE-2, and REGAIN were 120 mg monthly (with a 240-mg loading dose) or 240 mg monthly,1-3 and

  • CONQUER was 120 mg monthly (with a loading dose of 240 mg).4

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.5 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Measures of Functioning and Disability

In the phase-3 migraine prevention studies

  • functioning was measured using the MSQ version 2.1, and

  • disability was measured using the MIDAS test.6-8

The MSQ Role Function-Restrictive domain was considered the most relevant to measure treatment benefit related to the degree that performance of day-to-day activities is limited by migraine.9 The methods applied to the MSQ Role Function-Restrictive domain align with evidence requirements for an FDA label claim. 

For additional details about the instruments used, see  

Function and Disability at Baseline

Baseline monthly migraine headache days experienced by patients were

  • 9.1 days in the EVOLVE studies10

  • 19.4 days in the REGAIN study,3 and

  • 13.2 days in the CONQUER study.4

The baseline monthly migraine headache days were comparable between treatment groups in these studies.1-4

Baseline function and disability are summarized in Table 1.

In these studies, the mean baseline scores on the

  • MSQ Role Function-Restrictive domain represent considerable functional impairment, and

  • MIDAS represent severe disability in the EVOLVE studies, and very severe disability in the REGAIN and CONQUER studies.6-8,11

Table 1. Baseline Function and Disability Measures

Variable, Mean (SD)

EVOLVE-16
N=858

EVOLVE-26
N=915

REGAIN7
N=1113

CONQUER4,8
N=262

MSQ Role Function-Restrictive score

PBO

n=431
52.9 (15.4)

n=456
51.4 (15.7)

n=546
38.4 (17.2)

n=230
44.0 (18.5)

GMB 120 mg

n=212
51.4 (16.2)

n=231
52.5 (14.8)

n=272
39.3 (17.3)

n=232
45.8 (16.0)

GMB 240 mg

n=208
48.8 (16.8)a

n=222
51.7 (16.3)

n=272
38.9 (17.3)

NAb

MIDAS total score

PBO

n=431
31.8 (27.3)

n=456
34.3 (31.0)

n=546
68.7 (57.4)

n=230
51.0 (45.5)

GMB 120 mg

n=212
32.9 (28.2)

n=231
30.9 (27.9)

n=272
62.5 (49.5)

n=232
50.9 (46.0)

GMB 240 mg

n=208
36.1 (27.8)

n=222
32.8 (28.8)

n=272
69.2 (64.1)

NAb

Abbreviations: GMB = galcanezumab; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; NA = not applicable; PBO = placebo.

a p<.05 vs PBO.

b The CONQUER study did not have a GMB 240-mg treatment arm.

Effect on Function and Disability

In all studies, compared with placebo, patients treated with galcanezumab experienced less

  • functional impairment (measured by MSQ Role Function-Restrictive), and

  • disability (measured by MIDAS).4,6-8

With the exception of the galcanezumab 240-mg dose in the REGAIN study on the MIDAS, all doses of galcanezumab showed statistically significant differences compared with placebo on these measures.4,6-8

Changes on measures of function and disability are summarized in Table 2.

Responder analyses were conducted based on the MSQ Role Function-Restrictive domain and MIDAS in the EVOLVE-1, EVOLVE-2, and REGAIN studies. Responders were defined as

  • an increase score of +10.9 on the MSQ Role Function-Restrictive domain, or

  • at least 50% improvement from baseline in the MIDAS total score.6,7

There were statistically significantly more patients meeting response thresholds for both doses of galcanezumab compared with placebo (all p<.05) across all 3 studies on the

  • MSQ Role Function-Restrictive domain (88%-91% in the EVOLVE studies, and 75%-78% in the REGAIN study), and

  • MIDAS total score (73%-80% in the EVOLVE studies, and 45%-49% in the REGAIN study).6,7

Table 2. Changes in Patient Functioning and Disability Scores During Treatment

 

EVOLVE-16

EVOLVE-26

REGAIN7

CONQUER4,8

MSQ Role Function-Restrictive score, LSM change (SE) from baselinea

PBO

n=425
24.7 (1.1)

n=450
19.7 (0.9)

n=494
16.8 (1.2)b

n=230
10.7 (1.3)

GMB 120 mg 

n=210
32.4 (1.3)bc

n=226
28.5 (1.2)bc

n=252
21.8 (1.4)bc

n=232
23.2 (1.4)d

GMB 240 mg 

n=208
32.1 (1.3)bc

n=220
27.0 (1.2)bc

n=253
23.1 (1.6)bc

NAe

MIDAS total score, LSM change (SE) from baselinef

PBO

n=425
-14.9 (1.4)b

n=450
-12.0 (1.3)b

n=504
-11.5 (3.4)

n=230
-3.3 (3.3)

GMB 120 mg

n=210
-21.2 (1.7)bc

n=226
-21.2 (1.6)bc

n=254
-20.3 (4.1)g

n=232
-21.1 (3.3)d

GMB 240 mg

n=208
-20.1 (1.7)bg

n=220
-20.2 (1.6)bc

n=258
-17.0 (4.1)

NAe

Abbreviations: GMB = galcanezumab; LSM = least squares mean; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; NA = not applicable; PBO = placebo.

a For the EVOLVE-1 and EVOLVE-2 studies, reflects the change averaged over months 4-6. For the REGAIN and CONQUER studies, reflects the change at month 3.

b p<.001 vs baseline.

c p<.001 vs PBO.

d p<.0001 vs PBO.

e The CONQUER study did not have a GMB 240 mg treatment arm.

f For the EVOLVE-1 and EVOLVE-2 studies, reflects change at month 6. For the REGAIN and CONQUER studies, reflects the change at month 3.

g p<.05 vs PBO.

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.5

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.5

References

1. 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

2. 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

3. 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

4. Mulleners 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

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

6. Ford JH, Ayer DW, Zhang Q, et al. Two randomized migraine studies of galcanezumab: effects on patient functioning and disability. Neurology. 2019;93(5):e508-e517. http://dx.doi.org/10.1212/wnl.0000000000007856

7. Ford J, Tassorelli C, Leroux E, et al. Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN). Qual Life Res. Published online September 15, 2020. http://dx.doi.org/10.1007/s11136-020-02623-1

8. Tepper SJ, Ailani J, Ford JH, et al. Effects of galcanezumab on health-related quality of life in patients with treatment-resistant migraine: results from CONQUER study. Eur J Neurol. 2020;27(S1):445. 6th Congress of the European Academy of Neurology, Virtual 2020 abstract EPR3051. http://dx.doi.org/10.1111/ene.14307

9. Jhingran P, Osterhaus JT, Miller DW, et al. Development and validation of the Migraine‐Specific Quality of Life Questionnaire. Headache. 1998;38(4):295-302. https://doi.org/10.1046/j.1526-4610.1998.3804295.x

10. Detke HC, Millen BA, Zhang Q, et al. Rapid onset of effect of galcanezumab for the prevention of episodic migraine: analysis of the EVOLVE studies. Headache. 2020;60(2):348-359. http://dx.doi.org/10.1111/head.13691

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

12. Stewart WF, Lipton RB, Kolodner K, et al. Reliability of the Migraine Disability Assessment score in a population-based sample of headache sufferers. Cephalalgia. 1999;19(2):107-114. https://doi.org/10.1046/j.1468-2982.1999.019002107.x

13. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56(suppl 1):S20-S28. http://dx.doi.org/10.1212/WNL.56.suppl_1.S20

14. Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS). Cephalalgia. 2011;31(3):301-315. http://dx.doi.org/10.1177/0333102410381145

Glossary

FDA = Food and Drug Administration

MIDAS = Migraine Disability Assessment

MSQ = Migraine-Specific Quality of Life Questionnaire

Appendix

MSQ

The MSQ instrument includes a 14-item questionnaire that measures 3 independent domains including

  • Role Function-Restrictive

  • Role Function-Preventive, and

  • Emotional Function.9

The MSQ measures the impact of migraine on

  • work or daily activities

  • relationships with family and friends

  • leisure time

  • productivity

  • concentration

  • energy

  • tiredness, and

  • emotional well-being.9

Scoring on each domain ranges from 0 to 100, with higher scores indicating better functioning.9 In other words, patients with higher scores on the MSQ experience fewer restrictions on the performance of day-to-day activities.

MIDAS

The MIDAS is a patient-rated scale that was designed to quantify migraine-related disability associated with missed or reduced productivity at work or home and social events.12,13

A higher value is indicative of more disability.12,13

Migraine-related disability categories derived from the total MIDAS score are

  • minimal or infrequent disability” for scores 0 to 5

  • mild or infrequent disability” for scores 6 to 10

  • moderate disability” for scores 11 to 20

  • severe disability” for scores 21 to 40, and

  • very severe disability” for scores 41 to 270.13,14

Datum fӧr senaste ӧversyn 2020 M11 04


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