Emgality® ▼ (galcanezumab): Respons efter fortsatt behandling hos primära non-responders

Additional Information

The treatment benefit should be assessed within 3 months after initiation of treatment. Any further decision to continue treatment should be taken on an individual patient basis. Evaluation of the need to continue treatment is recommended regularly thereafter.¹

The decision to discontinue treatment with galcanezumab in a patient who is not responding well must be based on the clinical judgment of the prescribing healthcare practitioner. As discussed below, factors contributing to galcanezumab treatment response or nonresponse have yet to be elucidated. Reductions in MHD is only one measure of response and there may be other benefits to treatment, determined between a patient and their clinician, that justify ongoing treatment despite not reaching a threshold reduction in MHD.²

Phase 3 Randomized, Double-Blind, Placebo-Controlled Migraine Prevention Studies

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),^3,4 and

• chronic migraine (REGAIN).⁵

The studies had a duration of

• 6 months for prevention of episodic migraine,^3,4 and

• 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.⁵ 

Patients were randomized at the beginning of double-blind treatment in a 2:1:1 ratio to receive monthly subcutaneous injections of 

• placebo

• galcanezumab 120 mg with a loading dose of 240 mg, or

• galcanezumab 240 mg.^3-5 

• 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 included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

The primary endpoint was the overall mean change from baseline in the number of monthly MHDs over

• 6 months for episodic migraine, and

• 3 months for chronic migraine.^3-5

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine

A post hoc analysis examined response after continued galcanezumab treatment in patients who did not achieve "good" early improvement after 1 or 2 months of randomized, double-blind treatment.²

Good early improvement was defined as

• ≥50% reduction from baseline in MHD in the episodic migraine studies, and

• ≥30% reduction from baseline in MHD in the chronic migraine study.²

A ≥30% reduction from baseline in MHD for chronic migraine can be clinically meaningful and was adopted for this analysis.² 

This analysis included

• 879 galcanezumab-treated patients from EVOLVE-1 and EVOLVE-2 (pooled 120-mg and 240-mg doses), and

• 555 galcanezumab-treated patients from REGAIN (pooled 120-mg and 240-mg doses).²

Additional information about the design of this post hoc analysis is available in the publication.²

Early Improvement Categories

Responses of patients who did not achieve "good" early improvement were subcategorized based on the response a patient indicated within the first or second month of treatment (Table 1).²

The protocol-defined secondary response endpoint was defined as a reduction from baseline of

• ≥50% in monthly MHD for episodic migraine, and

• ≥30% in monthly MHD for chronic migraine.²

Table 1. Early Improvement Categories in Patients who did not Achieve Good Early Improvement²

Category	Episodic Migraine	Chronic Migraine
Modest early improvement	>30% to <50% fewer MHD	>10% to <30% fewer MHD
Limited early improvement	>10% to ≤30% fewer MHD	N/A
Minimal or no early improvement	≤10% fewer MHD to ≤10% more MHD	≤10% fewer MHD to ≤10% more MHD
Worsening	>10% more MHD	>10% more MHD

Abbreviations: MHD = migraine headache day; N/A = not applicable.

Outcomes With Continued Treatment in Patients who did not Achieve Good Response After Months 1 or 2

Outcome definitions after continued treatment with galcanezumab through the double-blind treatment period are included below (Table 2).²

Table 2. Continued Treatment Outcome Definitions²

Category	Episodic Migraine	Chronic Migraine
Better Response	≥75% fewer MHD	≥50% fewer MHD
Good Response	≥50% fewer MHD	≥30% fewer MHD
Little-to-no Response	≤10% fewer MHD	≤10% fewer MHD

Abbreviation: MHD = migraine headache day.

Results

In the episodic migraine studies, 48.7% and 67.0% of patients met protocol-defined response at months 1 and 2, respectively. In the chronic migraine study, 44.9% and 56.8% of patients met protocol-defined response at months 1 and 2, respectively. This analysis included only patients who did not meet protocol-defined response at month 1, and month 1 or month 2. The percentages of patients with episodic or chronic migraine by improvement after 1 and 2 months of galcanezumab treatment are provided below: Table 3.² 

Table 3. Percentage of Patients With Episodic or Chronic Migraine by Improvement After 1 Month and 2 Months of Galcanezumab Treatment² 

	EVOLVE-1 and EVOLVE-2 N=878a	REGAIN N=555
NR-1
Protocol-defined Responseb	48.7%	44.9%
Modest Improvement	17.7%	20.9%
Limited Improvement	12.3%	---
Minimal/no improvement	9.7%	24.0%
Worsening	11.6%	10.3%
NR-2
Protocol-defined Responseb	67.0%	56.8%
Modest Improvement	5.7%	12.8%
Limited Improvement	11.2%	---
Minimal/no improvement	7.6%	21.8%
Worsening	8.5%	8.6%

Abbreviations: MHD = migraine headache day; NR-1 = patients without response after month 1 of galcanezumab treatment; NR-2 = patients without response after month 1 or month 2 of galcanezumab treatment.

^a One patient in the episodic group was excluded because of missing month 1 monthly headache day values.

^b Defined as reduction from baseline in monthly MHD of ≥50% for episodic migraine studies, or ≥30% in the chronic migraine study. These patients were not subject to further post hoc analysis.

In the episodic migraine studies, of the NR-1 (patients without response after month 1 of galcanezumab treatment) patients having "modest" early improvement,

• 62% achieved “good”, and

• 20% achieved “better” responses with continued treatment: Figure 1.² 

A percentage of patients with “limited” (43%) or “minimal/no” (34%) early improvement, or “worsening” (20%) achieved a “good” response after continued treatment.²

In the chronic migraine study, of the NR-1 patients having "modest" early improvement,

• 38% achieved "good", and

• 13% achieved "better" responses with continued treatment: Figure 1.²

A good response was achieved for a percentage of patients with "minimal/no" early improvement (17%).

Similar patterns were observed for the NR-2 subset (patients without response after month 1 or month 2 of galcanezumab treatment) in episodic migraine and chronic migraine, however the percentages were lower: Figure 2.² 

Figure 1. Response Outcome in NR-1 Groups After Continued Galcanezumab Treatment*²

Abbreviations: MHD = migraine headache day; NR-1 = patients without response (with response defined as ≥30% reduction of MHD) after month 1 of galcanezumab treatment.
*Continued treatment: remaining months 2 through 6 (episodic); remaining months 2 through 3 (chronic).

Figure 2. Response Outcomes in NR-2 Groups After Continued Galcanezumab Treatment*²

Abbreviations: MHD = migraine headache day; NR-2 = patients without response (with response defined as ≥30% reduction of MHD) after month 1 or month 2 of galcanezumab treatment.
*Continued treatment: remaining months 2 through 6 (episodic); remaining months 2 through 3 (chronic).

It was concluded that galcanezumab-treated patients with episodic or chronic migraine who did not respond following 1 or 2 months of treatment

• appear to have a reasonable likelihood of continued improvement in months following initial treatment, and

• patients with greater early improvement were more likely to achieve improved responses with continued treatment.²

While a small percentage of patients with episodic or chronic migraine who experienced worsening MHD following initial treatment responded with continued dosing, most patients do not show substantial response with continued treatment.²

More information on the analysis and results are included in the open-access article.²

Therapeutic Indication

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

References

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

2. Nichols R, Doty E, Sacco S, et al. Analysis of initial nonresponders to galcanezumab in patients with episodic or chronic migraine: results from the EVOLVE-1, EVOLVE-2, and REGAIN randomized, double-blind, placebo-controlled studies. Headache. 2019;59(2):192-204. http://dx.doi.org/10.1111/head.13443

3. 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

4. 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

5. 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

Glossary

MHD = migraine headache day

▼ 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.