Eptinezumab-jjmr (Vyepti)

Number: 0970

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses eptinezumab-jjmr (Vyepti) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of Vyepti is required of all Aetna participating providers and members in applicable plan designs. For precertification, call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies for eptinezumab-jjmr (Vyepti). For information on site of service, see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

1. Criteria for Initial Approval

   Aetna considers eptinezumab-jjmr (Vyepti) medically necessary for the preventive treatment of migraine in an adult member when either of the following criteria are met:

   1. The member experienced an inadequate treatment response with an 8-week trial of any of the following: Antiepileptic drugs (AEDs) (e.g., divalproex sodium, topiramate, valproate sodium), Beta-adrenergic blocking agents (e.g., metoprolol, propranolol, timolol, atenolol, nadolol), Antidepressants (e.g., amitriptyline, venlafaxine); or
   2. The member experienced an intolerance or has a contraindication that would prohibit an 8-week trial of any of the following: Antiepileptic drugs (AEDs) (e.g., divalproex sodium, topiramate, valproate sodium), Beta-adrenergic blocking agents (e.g., metoprolol, propranolol, timolol, atenolol, nadolol), Antidepressants (e.g., amitriptyline, venlafaxine);

   And when the following criterion is met:

   1. The requested drug will not be used concurrently with another calcitonin gene-related peptide (CGRP) receptor antagonist (e.g., Aimovig, Ajovy, Emgality).

   Aetna considers all other indications as experimental and investigational.

2. Continuation of Therapy

   Aetna considers continuation of eptinezumab-jjmr (Vyepti) therapy medically necessary in adult members requesting reauthorization for preventive treatment of migraine if the member received at least 3 months of treatment with the requested drug and had a reduction in migraine days per month from baseline, and the requested drug will not be used concurrently with another calcitonin gene-related peptide (CGRP) receptor antagonist (e.g., Aimovig, Ajovy, Emgality).

Dosage and Administration

Vyepti is supplied as 100 mg/mL solution in a single-dose vial for intravenous use.

The recommended dosage of Vyepti is 100 mg administered as an intravenous infusion over approximately 30 minutes every 3 months. Some individuals may benefit from a dosage of 300 mg administered by intravenous infusion every 3 months.

Source: Lundbeck Seattle BioPharmaceuticals, 2022

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
+96366	each additional hour (List separately in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J3032	Injection, eptinezumab-jjmr, 1 mg
Other HCPCS codes related to the CPB:
Aimovig, Emgality - no specific code
J3031	Injection, fremanezumab-vfrm, 1 mg
ICD-10 codes covered if selection criteria are met:
G43.001 - G43.919	Migraine

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Background

U.S. Food and Drug Administration (FDA)-Approved Indication

• Vyepti is a calcitonin gene-related peptide antagonist indicated for the preventive treatment of migraine in adults.

Eptinezumab-jjmr is available as Vyepti (Lundbeck Seattle BioPharmaceuticals, Inc.), which is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. 

Vyepti is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients. Vyepti carries warnings and precautions for hypersensitivity reactions. Reactions have included angioedema, urticaria, facial flushing, and rash. The most common adverse reactions (greater than or equal to 2% and 2% or greater than placebo) include nasopharyngitis and hypersensitivity (Lundbeck Seattle BioPharmaceuticals, 2022).

Calcitonin Gene-Related Peptide Antagonists for Migraine Prevention

Migraine is a chronic neurologic disease that affects approximately 12 percent of the general population and is more frequently seen in women. Migraine-related symptoms are addressed with acute treatments, preventive treatments, or both. According to the 2019 American Headache Society AHS Consensus Statement, the goals of migraine prevention are to:

• Reduce attack frequency, severity, duration, and disability
• Improve responsiveness to and avoid escalation in use of acute treatment
• Improve function and reduce disability
• Reduce reliance on poorly tolerated, ineffective, or unwanted acute treatments
• Reduce overall cost associated with migraine treatment
• Enable patients to manage their own disease to enhance a sense of personal control
• Improve health-related quality of life (HRQoL)
• Reduce headache-related distress and psychological symptoms.

Although none of the currently available oral preventive treatments were designed specifically for migraine, and many oral preventive treatments have limited to moderate efficacy, moderate to high rates of adverse events (AEs), contraindications, or interactions, the 2012 report of the Quality Standards Subcommittee of the American Academy of Neurology (AAN) and the American Headache Society (AHS) state that the following oral treatments have either established efficacy or probable efficacy and should be offered for migraine prevention: antiepileptic drugs (divalproex sodium, valproate sodium, topiramate); beta-blockers (metoprolol, propranolol, timolol, atenolol, nadolol); and onabotulinum toxin A (Botox) (Silberstein 2012).

More recently, a new class of injectable therapies have been approved for migraine prophylaxis in adults in the United States. These calcitonin gene-related peptides (CGRP) monoclonal antibodies include: erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab- (Vyepti). Emgality is also indicated for the treatment of episodic cluster headaches in adults. The first three are subcutaneous injectable therapies, whereas Vyepti is administered via intravenous administration. The benefits associated with the injectable route of administration compared with traditional oral prophylactic therapy options include the lack of need for slow dose escalation, the rapid onset of therapeutic benefits, and the favorable tolerability profiles (AHS 2019).

On May 17, 2018, the U.S. Food and Drug Administration approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. The treatment is given by once-monthly self-injections. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide, a molecule that is involved in migraine attacks. The effectiveness of Aimovig for the preventive treatment of migraine was evaluated in three clinical trials. The first study included 955 participants with a history of episodic migraine and compared Aimovig to placebo. Over the course of six months, Aimovig-treated patients experienced, on average, one to two fewer monthly migraine days than those on placebo. The second study included 577 patients with a history of episodic migraine and compared Aimovig to placebo. Over the course of three months, Aimovig-treated patients experienced, on average, one fewer migraine day per month than those on placebo. The third study evaluated 667 patients with a history of chronic migraine and compared Aimovig to placebo. In that study, over the course of three months, patients treated with Aimovig experienced, on average, 2 ½ fewer monthly migraine days than those receiving placebo. The most common side effects that patients in the clinical trials reported were injection site reactions and constipation (FDA 2018).

On September 14, 2018, the FDA approved fremanezumab (Ajovy) for the prevention of migraine in adults based on results from two clinical trials, Trial 1/NCT02629861 and Trial 2/NCT02621931, in a total of 1986 patients with chronic or episodic migraine headaches. Investigators observed that fremanezumab reduced monthly migraines by >50% in roughly 45% of patients with episodic migraine and in about 40% of patients with chronic migraine. Injection site reactions were among the most common adverse events (>5% and greater than placebo) recorded in the clinical trials. Other hypersensitivity reactions observed include pruritus, rash, and urticaria. Most hypersensitivity reactions were mild to moderate, but some led to discontinuation (FDA 2018).

On September 27, 2018 the U.S. Food and Drug Administration approved galcanezumab-gnlm (Emgality) based its approval of galcanezumab on the results of three phase 3 double-blind, randomized, placebo-controlled clinical trials that evaluated its safety and efficacy in a cohort of episodic migraine patients and chronic migraine patients. The first two six-month trials, EVOLVE-1 and EVOLVE-2, included more than 1,700 patients with episodic migraine, defined as four to 14 migraine headache days per month. In EVOLVE-1, the drug significantly reduced monthly migraine days: 4.7 days for 120 mg and 4.6 days for 240 mg versus 2.8 days for placebo (p<0.001.). Similarly, in EVOLVE-2, participants had a mean reduction of 4.3 days for 120 mg and 4.2 days for 240 mg versus 2.3 days for placebo (p<0.001). Th third trial, REGAIN, tested both doses of galcanezumab over three months in patients with chronic migraine, defined as at least 15 headache days per month, with eight migraine days per month. Participants experienced greater reductions in migraine days than with placebo: 4.8 days for 120 mg and 4.6 days for 240 mg versus 2.7 days for placebo (p<0.001). Adverse events reported in all three trials, included injection site pain, reactions, and erythema. Subsequently, on June 04, 2019, the U.S. Food and Drug Administration also approved Emgality (galcanezumab-gnlm) solution for injection for the treatment of episodic cluster headache in adults (NeurologyToday 2018; Stauffer 2018).

On February 21, 2020, the FDA approved the intravenous eptinezumab-jjmr (Vyepti) for migraine prophylaxis in adults. Approval was based on results from two clinical studies: PROMISE-1 (NCT02559895) in episodic migraine and PROMISE-2 ( NCT02974153) in chronic migraine. The PROMISE-1 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-1) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with episodic migraine were randomized to eptinezumab 30 mg, 100 mg, 300 mg, or placebo for up to four intravenous (IV) doses administered every 12 weeks. The primary endpoint was change from baseline in monthly migraine days (MMDs) over weeks 1–12. A total of 888 patients received treatment across 84 study sites. Mean MMDs at baseline was ∼8.6 across treatment groups. Eptinezumab 100 mg and 300 mg met the primary endpoint, significantly reducing MMDs across weeks 1-12 compared with placebo (30 mg, -4.0; 100 mg, -3.9, p= 0.0182; 300 mg, -4.3; placebo, -3.2, p= 0.0001). Treatment-emergent adverse events were reported by 58.4% (30 mg), 63.2% (100 mg), 57.6% (300 mg), and 59.5% (placebo) of patients. Treatment-emergent adverse events reported by ≥2% of eptinezumab-treated patients at an incidence greater than placebo included: upper respiratory tract infection (30 mg, 11.4%; 100 mg, 9.9%; 300 mg, 10.3%; placebo, 7.2%), and fatigue (30 mg, 2.3%; 100 mg, 3.6%; 300 mg, 3.6%; placebo, <1%). The authors concluded that eptinezumab (100 mg or 300 mg) significantly reduced migraine frequency, was well tolerated, and had an acceptable safety profile when used for the preventive treatment of migraine in adults with episodic migraine (Ashina 2020). 

The PROMISE-2 study included adults with a history of chronic migraine (15 to 26 headache days per month, of which at least 8 were migraine days). A total of 1072 patients were randomized and received placebo (N=366), 100 mg eptinezumab (N=356), or 300 mg eptinezumab  (N=350) every 3 months for 6 months. Patients were allowed to use and to continue an established stable regimen of acute migraine or headache preventive medication (except onabotulinumtoxinA). Patients with a dual diagnosis of chronic migraine and medication overuse headache attributable to acute medication overuse (triptans, ergotamine, or combination analgesics greater than 10 days per month) were included in the study population. Patients using opioids or butalbital-containing products greater than 4 days per month were not allowed. The study excluded patients with a history of cardiovascular disease (hypertension, ischemic heart disease), neurological disease, or cerebrovascular disease. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD) over Months 1–3. Secondary endpoints included the percentages of patients with 50% or greater and 75% or greater reductions from baseline in monthly migraine days over Months 1–3. Patients had a median age of 41 years (range: 18 to 65 years), 88% were female, and 91% were white. Forty-one percent of patients were taking concomitant preventive medication for migraine. The mean migraine frequency at baseline was approximately 16.1 migraine days per month and was similar across treatment groups. Eptinezumab  treatment demonstrated statistically significant improvements compared to placebo for the primary efficacy endpoint. In 100mg-treated patients, changes from baseline in MMDs were −7.7 (p<0.0001) and −8.1 (p<0.0001) over Months 1–3 and Months 4–6, respectively. The ≥75% migraine RRs were: 30.9% (Month 1; p<0.0001), 26.7% (Months 1–3; p=0.0001), and 38.5% (Months 4–6). The ≥50% migraine RRs were: 57.6% (Months 1–3; p<0.0001) and 60.7% (Months 4–6). In 300mg-treated patients, changes from baseline in MMDs were −8.2 (p<0.0001) and −8.8 (p<0.0001) over Months1–3 and Months 4–6, respectively. The ≥75% migraine RRs were: 36.9% (Month1; p<0.0001), 33.1% (Months 1–3; p<0.0001), and 42.3% (Months 4–6). The ≥50% migraine RRs were: 61.4% (Months 1–3; p<0.0001) and 63.4% (Months 4–6). In placebo-treated patients, changes from baseline in MMDs were −5.6 and −6.1 over Months 1–3 and Months 4–6, respectively. The ≥75% migraine RRs were: 15.6% (Month 1), 15.0% (Months 1–3), and 22.7% (Months 4–6). The ≥50% migraine RRs were: 39.3% (Months 1–3) and 44.5% (Months 4–6). Rates of treatment-emergent adverse event were similar between groups. The authors concluded that eptinezumab significantly reduced MMDs over 3 months, which was further improved through Month 6 following a second quarterly infusion. Migraine RRs were greater with eptinezumab vs placebo over 3 months and were sustained or increased through Month 6. The eptinezumab safety profile was consistent with previous trials (Kudrow 2019).

Calcitonin Gene-Related Peptide Antagonists for Acute Migraine

An UpToDate review on “Acute treatment of migraine in adults” (Smith, 2020) states that “Several oral calcitonin gene-related peptide (CGRP) antagonist medications are emerging as treatment options for acute migraine attacks. In randomized controlled trials evaluating a single migraine attack, the CGRP antagonists rimegepant and ubrogepant were beneficial compared with placebo; both led to greater rates of freedom from pain and/or absence of the most bothersome migraine symptom at two hours. Ubrogepant (Ubrelvy) received FDA approval for the treatment of acute migraine in adults in December 2019, and rimegepant (Nurtec) received similar FDA approval in February 2020. However, given the short-term, single-attack design of these trials, long-term data are needed to determine safety and tolerability. In addition, their efficacy compared with existing acute migraine therapies (eg, triptans) is not yet known.”

Cui and associates (2015) stated that calcitonin gene-related peptide (CGRP) receptor antagonists, such as telcagepant, have been under investigation as a treatment for acute migraine. In a meta-analysis, these researchers evaluated the effectiveness of telcagepant versus placebo and triptans (zolmitriptan or rizatriptan).  Randomized controlled trials were identified from databases using the following search terms: migraine; calcitonin gene-related peptide; calcitonin gene-related peptide receptor antagonists; efficacy; safety, and telcagepant.  The primary outcome measure was pain freedom 2 hours after first treatment.  The secondary outcome measure was pain relief 2 hours after first treatment.  A total of 8 trials were included in the meta-analysis (telcagepant = 4,011 participants).  The difference in pain freedom at 2 hours significantly favored telcagepant over placebo (odds ratio = 2.70, 95 % confidence interval = 2.27-3.21, p < 0.001) and triptans over telcagepant (odds ratio = 0.68, 95% confidence interval = 0.56-0.83, p < 0.001). The difference in pain relief at 2 hours significantly favored telcagepant over placebo (odds ratio = 2.48, 95% confidence interval = 2.18-2.81, p < 0.001). The difference in pain relief at 2 hours did not significantly favor telcagepant over triptans or vice versa (OR = 0.76, 95 % CI: 0.57 to 1.01, p = 0.061).  The authors concluded that these findings indicated that telcagepant can be effective for treating acute migraine; and CGRP receptor antagonists represent a potentially important alternative means of treating acute migraine.

In a meta-analysis, Hong and Liu (2017) evaluated the effectiveness of CGRP antagonisms in treating acute migraine attack. PubMed, Cochrane Library, Web of Science and OvidSP were systematically searched up to April 9, 2015 for RCTs that dealt with the effectiveness of CGRP antagonisms in treating acute migraine attack.  The bias and quality of RCTs were assessed with Cochrane collaboration's tool for assessing risk of bias.  Reviewer manager 5.2 was utilized for data analysis.  A total of 13 publications matched the inclusion criteria, including 10 independent RCTs and 6,803 patients.  Pooled analysis indicated that CGRP antagonisms had better outcomes in number of patients with pain free at 2 hours, 2 to 24 hours sustained pain free, phonophobia free at 2 hours, patients with photophobia free at 2 hours and nausea free at 2 hours post-dose, as compared with placebo.  However, CGRP antagonisms were no superior than 5-HT agonists in the afore-mentioned indices.  The authors concluded that CGRP antagonisms may be an effective and promising treatment for acute migraine attack.

Huang et al (2019) evaluated the response rate of migraines by using anti-calcitonin gene-related peptide (anti-CGRP) for patients with migraines by searching three main medical databases up to 29 March 2019. No restriction on language and publication time were applied. Eligible trials included randomized clinical trials investigating a 50%, 75%, and 100% response rate of migraine patients after anti-CGRP intervention. The collected data were dichotomous, and risk ratios (RRs) with a 95% confidence interval (CI) were used to present the quantitative synthesis results. The systematic review identified 16 eligible randomized clinical trials (RCTs) with 9439 patients. Eight of the 16 trials with 2516 patients reported a 50% response rate, and the pooled results showed a significant benefit from anti-CGRP. However, the effects seem to gradually reduce from the first month (RR 1.99, 95% CI 1.59 to 2.49) to the third month (RR 1.48, 95% CI 1.26 to 1.75) of treatment. The magnitude of effect was influenced by the type of anti-CGRP, according to the test for differences between subgroups (I-square = 53%). The funnel plots and Egger's tests did not show serious small study effects in the results. In conclusion, the current evidences confirmed that anti-CGRP treatment can reduce migraine pain in the short term (within three months), but the long-term effect should be investigated in the future. Moreover, its effects may be influenced by the type and dose of anti-CGRP. Therefore, future studies should make direct comparisons among anti-CGRP medications.

Winner et al (2021) stated that IV eptinezumab is approved for migraine prevention in adults.  It has established onset of preventive effectiveness on day 1 after infusion.  In a randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase-III clinical trial, these researchers examined the effectiveness of and AEs related to eptinezumab when initiated during a migraine attack.  This study was carried out from November 4, 2019, to July 8, 2020, at 47 sites in the U.S. and the country of Georgia.  Subjects (aged 18 to 75 years) with a greater than 1-year history of migraine and migraine on 4 to 15 days per month in the 3 months before screening were treated during a moderate-to-severe migraine attack.  Subjects received eptinezumab, 100 mg (n = 238), or placebo (n = 242), administered intravenously within 1 to 6 hours of onset of a qualifying moderate-to-severe migraine.  Co-primary efficacy endpoints were time to headache pain freedom and time to absence of most bothersome symptom (nausea, photophobia, or phonophobia).  Key secondary endpoints were headache pain freedom and absence of most bothersome symptom at 2 hours after start of infusion.  Additional secondary endpoints were headache pain freedom and absence of most bothersome symptom at 4 hours and use of rescue medication within 24 hours.  Of 480 randomized and treated patients (mean age of 44 years; 84 % women), 476 completed the study.  Patients treated with eptinezumab versus placebo, respectively, achieved statistically significantly faster headache pain freedom (median of 4 hours versus 9 hours; hazard ratio [HR], 1.54 [p < 0.001]) and absence of most bothersome symptom (median of 2 hours versus 3 hours; HR, 1.75 [p < 0.001]).  At 2 hours after infusion, in the respective eptinezumab and placebo groups, headache pain freedom was achieved by 23.5 % and 12.0 % (between-group difference, 11.6 % [95 % CI: 4.78 % to 18.31 %]; odds ratio [OR], 2.27 [95 % CI: 1.39 to 3.72]; p < 0.001) and absence of most bothersome symptom by 55.5 % and 35.8 % (between-group difference, 19.6 % [95 % CI: 10.87 % to 28.39 %]; OR, 2.25 [95 % CI: 1.55 to 3.25]; p < 0.001).  Results remained statistically significant at 4 hours after infusion.  Statistically significantly fewer eptinezumab-treated patients used rescue medication within 24 hours than did placebo patients (31.5 % versus 59.9 %, respectively; between-group difference, -28.4 % [95 % CI: -36.95 % to -19.86 %]; OR, 0.31 [95 % CI: 0.21 to 0.45]; p < 0.001).  Treatment-emergent AEs occurred in 10.9 % of the eptinezumab group and 10.3 % of the placebo group; the most common was hypersensitivity (eptinezumab, 2.1 %; placebo, 0 %).  No treatment-emergent serious AEs occurred.  The authors concluded that among patients eligible for preventive migraine therapy experiencing a moderate-to-severe migraine attack, treatment with IV eptinezumab versus placebo shortened time to headache and symptom resolution.  Moreover, these researchers stated that feasibility of administering eptinezumab treatment during a migraine attack and comparison with alternative treatments remain to be established.

The authors stated that this study had several drawbacks.  First, this study did not include a run-in period to define the preceding migraine frequency but paralleled clinical practice in measuring migraine days based on a history of 4 to 15 migraine days per month in the 3 months before screening.  This requirement ensured the enrollment of patients who could be considered candidates for preventive treatment in line with current guidance; but was less stringent than controlled daily diaries to establish migraine frequency.  Second, this inclusion criterion (4 to 15 migraine days per month) also diverged from current guidance for studies of acute migraine treatment -- which excluded patients with chronic migraine (limiting the population to 2 to 8 migraine days per month) -- resulting in a population with more frequent and severe migraine than those who were included in acute migraine trials and underscoring that the methodology of this study was intended instead to show that eptinezumab could be used to treat and prevent migraine in the population of patients eligible for preventive treatment.  Third, the generalizability of these study results may be limited due to the high proportions of women, White, and non-Hispanic or non-Latino patients enrolled.  Fourth, this study did not include an active control, precluding direct comparisons between eptinezumab and other migraine treatments administered under these conditions.  Fifth, the practical challenges of delivering eptinezumab during an acute migraine attack (e.g., access to an infusion center, insurance coverage issues) may be a limitation to the clinical usefulness of this study.

McAllister et al (2022) noted that demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management.  In a randomized, double-blind, placebo-controlled trial, these investigators examined the impact of eptinezumab on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.  This trial was carried out between 2019 and 2020 in adults with 1-year or more history of migraine and 4 to 15 migraine days per month in the 3 months before screening.  Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100-mg or placebo within 1 to 6 hours of a qualifying migraine attack onset.  The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4.  A post-hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 hours after infusion start.  Of 480 patients enrolled and treated, 476 completed the study and were included in this analysis.  Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8).  At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, - 8.7; placebo, - 4.5; mean [95 % CI] difference from placebo: - 4.2 [- 5.75, - 2.63], p < 0.0001), with greater reductions in each item score versus placebo (p < 0.001 all comparisons).  Change in HIT-6 total score in the subgroup with 2-hour headache pain freedom was - 13.8 for the eptinezumab group compared with - 4.9 for the placebo group.  mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95 % CI] difference: 0.9 [0.3, 1.5], p < 0.01).  More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3 % versus 25.9 %).  The authors concluded that preventive migraine treatment with eptinezumab initiated during a migraine attack provided clinically meaningful improvements in several patient-reported outcome measures (PROMs) as early as 4 weeks after infusion.  These benefits were especially noticeable in those patients who reported headache pain freedom at 2 hours, highlighting the significance of experiencing the early onset of effect with eptinezumab.  Furthermore, patients treated with eptinezumab relative to those receiving placebo reported greater effectiveness of their acute medication used after initiation during a migraine attack, findings that may raise the standards for preventive treatments and provide promising outcomes for patients suffering from migraine.

The authors stated that this study had several drawbacks.  First, the data for this trial were generated in the clinical trial setting; thus, subjects may differ from those in general practice, potentially limiting the overall generalizability of the results.  Second, patients reported a higher migraine severity and impact than previously reported in similar patient populations.  Third, because changes in MMDs -- a traditional outcome for migraine preventive treatments -- were not captured over longer term (e.g., over 12 weeks) using a daily electronic diary, changes in PROMs could not be compared to reductions in MMDs.  Fourth, while PROM assessment demonstrated a clinically meaningful benefit at week 4, no PROMs were captured after 12 weeks (the approved treatment interval for eptinezumab), limiting the long-term applicability of the results since it likely takes longer than 4 weeks for patients to adjust their expectations after initiation of preventive treatment.

Eptinezumab for the Treatment of Status Migrainosus

Ray et al (2022) noted that status migrainosus is a disabling complication of migraine that often leads to hospitalization.  For patients who fail to respond to simple analgesia, triptans and intravenous prochlorperazine or chlorpromazine, there are limited therapeutic options, and a paucity of high-quality evidence to guide clinical practice.  Eptinezumab, an IV monoclonal antibody specific for the CGRP ligand that achieves maximal plasma concentration immediately following administration and may improve migraines from day 1.  Moreover, IV lignocaine is an anesthetic medication used in the treatment of status migrainosus, often requiring prolonged admissions and with potential cardiac AEs.  The objective of this trial is to examine the safety and effectiveness of eptinezumab in the treatment of status migrainosus in comparison to IV lidocaine.  Status migrainosus inpatient treatment with eptinezumab (SMITE) is a randomized, controlled, single-center clinical trial that will be carried out in a parallel design with an active comparator performed in Melbourne, Australia.  This study will randomize 40 patients (1:1) to receive either eptinezumab or an infusion of IV lignocaine for up to 5 days.  It will examine the effect of eptinezumab compared with IV lignocaine in aborting status migrainosus, with the primary outcome of time from infusion until resolution of pain.  It will explore several secondary measures including change in health resource utilization, effect on patient reported outcomes of migraine disability and the safety and tolerability of each medication.  This study has been reviewed and approved by the Human Research Ethics Committee of Alfred Health, local reference number 443/21, and all participants will provide informed consent for participation in the trial and dissemination of results.  The results of this trial will be disseminated via peer-reviewed journals, conference presentations and social media.

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References