A prospective real-world analysis of intravenous eptinezumab in migraine management: the first UK experience

Abstract

Background

Clinical trials have shown the safety and statistical superiority of intravenous eptinezumab to placebo in migraine prevention in adults. However, data in real-world settings is sparse.

Methods

This is a prospective open-label single centre real-world analysis aiming to establish the effectiveness of intravenous eptinezumab 100 mg in patients with migraine who were treated for up to six months as per the National Institute of Care and Health Excellence (NICE) guidelines in the United Kingdom (UK).

Results

Of 130 patients treated between February 2023 and February 2025, 119 patients with migraine (chronic migraine: 112, 94%), who had completed a three month follow up and submitted their headache diary following the first eptinezumab infusion were analysed. Patients failed to respond/tolerate an average of 10.2 ± 4.5 preventive treatments and 80 patients (67%) did not respond or tolerate one or two calcitonin gene related peptide (CGRP) targeting therapies prior to Eptinezumab. After one eptinezumab infusion, 61 (51%), 41 (35%) and 15 (13%) of patients achieved at least a 30%, 50% and 75% reduction in their mean monthly migraine days (MMDs), respectively. The average reduction in MMD was 5.4 days (P < 0.001). Out the 76 patients who had the six-month review after the second infusion, 48 (63%), 33 (43%) and 14 (18%) of patients achieved at least a 30%, 50% and 75% reduction, respectively, in their MMD, with an average reduction in MMD of 6.3 days (P < 0.001). There was an average reduction of the Headache Impact Test 6 (HIT-6) score of 5.3 and 6.3 respectively at months 3 and 6 post-infusions (P < 0.001). Patients who were naive to any other anti-CGRP monoclonal antibodies (mAb) treatment were more likely to be eptinezumab responders (30% reduction in MMD) than those who failed to respond to previous anti-CGRP mAbs both at 3 and 6 months (3 month responders: 74% vs. 40; 6 months responders: 56% vs. 33%, p = 0.001). After the first treatment, 24 patients (20%) reported 34 treatment-related adverse events. After the second treatment, nine patients reported ten adverse events. Six patients (5%) discontinued eptinezumab because of side effects.

Conclusion

In real world settings, intravenous eptinezumab may be an effective and well tolerated treatment option for patients with migraine who fail multiple treatments including other anti-CGRP mAbs.

Introduction

Migraine is a common neurological disorder and a leading cause of disability amongst all neurological diseases [1]. The most disabling subtype of migraine is chronic migraine (CM), clinically defined by the presence of ≥ 15 headache days/month for ≥ 3 months, with at least half of them fulfilling the criteria for migraine [2]. Compared to episodic migraine (EM), CM is associated with significantly greater disability, higher rates of comorbidity, and increased direct and indirect costs [3].

The calcitonin gene related peptide (CGRP) targeting therapies are now established as both acute and preventive migraine treatments [4, 5]. The most recent anti-CGRP monoclonal antibody (mAb) is eptinezumab (Lundbeck Seattle BioPharmaceuticals, Bothell, WA, USA), which is the only intravenous anti-CGRP mAb. This unique pharmacokinetic profile accounts for its rapid onset of action, as evidenced by the ability to shorten the time to headache and symptom resolution compared to placebo in moderate to severe migraine attacks [6, 7]. With a terminal half-life of 27 days and modest exposure metrics required to reach concentrations achieving 90% of the maximum change in effect (EC90), eptinezumab is suitable for quarterly administration at doses of both 100 mg and 300 mg.

The safety, efficacy and sustainability of the effect of eptinezumab has been demonstrated in phase 3 clinical trials in EM and CM (PROMISE 1 and 2 trials) and in the subpopulation of patients with documented previous preventive treatment failures (DELIVER trial) [8–10]. In March 2023 eptinezumab 100 mg was approved in the United Kingdom (UK) for the prevention of migraine in adults with at least four migraine days a month, who have failed at least three preventive treatments, following the National Institute of Care and Health Excellence (NICE) guidelines [11].

The present prospective single-centre analysis aims to investigate in a real life setting the effectiveness of IV eptinezumab in migraine patients.

Methods

This is a registered prospective clinical audit conducted at the Headache Service at Guy’s and St Thomas’ NHS Foundation Trust, London, UK, approved by the Guy’s and St Thomas’ NHS Foundation trust audit committee (Audit number: 16827). This project aims to evaluate the effectiveness, safety and tolerability of eptinezumab in adults with at least four migraine days per month. New patients who initiated eptinezumab between February 2023 and February 2025, were included in the audit.

Participants

Adult patients meeting the International Headache Society (IHS) criteria for EM or CM who failed at least three preventive treatments were included in the audit [2]. For patients who underwent a trial with botulinum toxin type A (BoNT/A), failure to obtain at least 30% reduction in headache days after two sets of injections was considered treatment failure as per (NICE) UK guidance [12]. For patients who underwent a trial with another anti-CGRP mAb, failure to obtain at least a 30% and 50% reduction in migraine days after at least three consecutive months of injections respectively for CM and EM, was considered treatment failure. As per our CGRP treatment pathway, patients who are switched from an anti-CGRP mAb to another, go through a wash out period of 4–6 weeks before starting the new treatment. This arbitrary period is the time when patients usually starts to experience a headache worsening (end of dose wearing off). Patients were allowed to continue oral preventive medications during treatment with eptinezumab, but they were asked not to change the dose until the effectiveness of eptinezumab was clearly established.

Audit under current national guidelines does not require research ethics committee review (http://www.hra-decisiontools.org.uk/research/).

Audit design

Figure 1 outlines the treatment audit profile. Eptinezumab 100 mg was infused intravenously, following dilution of the vial content in a 100 mL bag of 0.9% sodium chloride for injection, over 30 min, using an appropriate infusion set. Blood pressure (BP) and heart rate were measured in clinic at baseline and at every visit. Patients were kept within our inpatient waiting area for about 30 min following infusion to record potential immediate adverse events, before discharge.

Fig. 1.

Audit design and patients treatment pathway

Patients who met the 30% response rate [at least a 30% reduction in mean monthly migraine days (MMDs) after three consecutive months for the CM group] or the 50% response rate (at least 50% reduction in mean MMDs after three consecutive months for the EM group) were offered to continue the treatment with repeated 3-monthly (12 weekly-84 days) infusions. In selected cases with very difficult-to-treat migraine, a second treatment was offered despite patients not meeting the NICE criteria for treatment continuation.

Outcome measures

A migraine-specific diary and the Headache Impact Test-6 (HIT-6) score were used to capture efficacy and disability measures. Patients were required to produce a baseline headache diary and HIT-6 score for at least one month prior to treatment initiation and to continue filling the headache diary on a daily basis along with HIT-6 scores every month for the duration of the trial. Data was entered in an anonymised electronic macro database for analysis.

The main efficacy outcome was the 30% response and the 50% response rate for the three months following the treatment. We also evaluated changes from baseline in the mean MMD, mean monthly headache days (MHD) and mean monthly headache-free days. A “headache day” was defined as a day with headache lasting for ≥ 4 h and with a severity of ≥ 4/10 on a verbal rating scale (0, no head pain, 10 worst pain ever experienced). A “migraine day” was defined according to the IHS classification criteria [2]. A “mild headache day” was a day with headache lasting for < 4 h and with a severity of < 4/10 on a verbal rating scale. A “headache-free day” was defined as a day without any head pain. Changes in abortive treatment intake days was also evaluated. Patients were asked about the development of adverse events (AEs) immediately after each infusion and at every follow-up. Lack of efficacy was defined as < 30% or < 50% reduction in average MMD respectively for CM or EM patients as per NICE criteria.

Statistical analysis

All outcomes pre- and post-eptinezumab treatment were measured on a continuous scale. For all measures, data demonstrated a skewed distribution with a significant deviation from normal distribution (Kolmogorov-Smirnov test; P < 0.05). To express long term data as a linear graph, skewed data was reflected and transformed to make it normally distributed [13, 14]. ANOVA for repeated measures was used to compare the change in values over time. Paired t-test was used to compare any time point against baseline data. Independent t-test was used for independent group comparisons. A chi-square test of independence was conducted to examine the relationship between patients who were anti-CGRP mAb naïve and patients who had previous anti-CGRP mAb failure and likelihood of 30% reduction in mean MMDs. The null hypothesis was that response to eptinezumab and anti-CGRP/rec mAbs exposure are independent. Observed frequencies were recorded in a 2 × 2 contingency table. The chi-square statistic was calculated using SPSS 29.0.1, with 1 degree of freedom. All data are provided as mean (± standard error), unless stated otherwise.

Results

Demographic and baseline headache characteristics

A total of 130 patients received at least one intravenous infusion of eptinezumab during the audit period (Fig. 1). Of these, eight patients had other headache or facial pain conditions refractory to medical management but displayed some associated symptoms often described in migraine, namely photo-phonophobia, motion sensitivity and/or had a migraine biology (personal and/or family history of migraine). Completed headache diaries and HIT-6 at baseline were obtained from 121 patients [102 female; mean age, 44.7 Standard Deviation (SD) ± 13.5 years]. At the time of analysis for this report, 119 patients had their diary submitted to the clinic as part of their three-month follow up. Eighty-two patients received at least two eptinezumab treatments of which 76 had a six-month follow-up.

Demographic and clinical characteristics of the patients’ group included in the analysis at baseline are summarised in Table 1. All patients were medically refractory or resistant according to the European Headache Federation (EHF) consensus [15]. Eighty patients (67%) displayed a suboptimal response to one or more different anti-CGRP pathway mAb. Half of the patients reported a daily headache pattern at baseline. Of the 119 patients, 32 (27%) were classified as patients with medication overuse. At the time of the first infusion 72 (60%) of patients were taking concomitant preventive treatments; three-patients were on three-monthly onabotulinum toxin A injections when they initiated eptinezumab. Eighty-seven patients (73%) reported at least one comorbidity.

Table 1.

Demographic and clinical characteristics at baseline of 119 migraine patients treated with Eptinezumab

	Total number
Sex, Male/Female	20/99
Age (years), mean ± SD	45 ± 13
Migraine duration (years), mean ± SD	17 ± 14
Aura, N (%)	28 (24%)
Medication overuse, N (%)	32 (27%)
Chronic migraine/Episodic migraine	112/7
Chronic daily headache	59 (50%)
Number of preventive treatments failures	10.2 ± 4.5
Failed at least one CGRP targeting therapy	80 (67%)
Failed 2 CGRP targeting therapies	26 (22%)
Comorbidities:	87 (73%)
Chronic non-headache pain	37 (31%)
Psychiatric conditions	47 (40%)
Chronic fatigue	7 (6%)
Sleep disorders	19 (16%)
Cardiac dysautonomia	15 (13%)
Asthma	15 (13%)
Gastro-intestinal conditions	23 (19%)
≥ 1 comorbidities	87 (73%)
≥2 comorbidities	27 (23%)
≥3 comorbidities	15 (13%)

	Mean ± St. Er.
Migraine days	17.9± 0.8
Headache days	26.7 ± 0.5
Headache free days	3.8 ± 0.5
Abortive treatment intake day	11.9 ± 0.9
HIT-6 score	69.4 ± 0.6

CGRP calcitonin gene related peptide, HIT-6 headache impact test-6, N number, St. Er. standard error

Efficacy outcomes after first eptinezumab infusion – 3 months follow-up

Overall, during the entire 3-month observation period post-treatment initiation, MMD days and MHD were significantly reduced compared to baseline (MMDs: F_{3.6, 252.6} = 10.4, P < 0.00; MHDs: F_{2.6, 194.8} = 55.6, P < 0.001), as well as the number of abortive treatment intake days (F_{5.2, 343.2} = 2.5, P = 0.03). Additionally, the HIT-6 score was significantly reduced across the entire observational period (F_{6.0, 102} = 2.3, P = 0.04) (Fig. 2).

Fig. 2.

Three-month outcomes on all patients treated with eptinezumab. P values are indicated in the graphs; *, P < 0.001

Compared to baseline, the mean reduction in MMD over the three-month period was 5.4 days (from 17.9 ± 0.8 to 12.5 ± 0.5; t₁₀₉ = −4.4, P < 0.001). The mean reduction in MHD was 2.7 days (from 26.7 ± 0.5 to 24.2 ± 0.4; t₁₀₉ = −2.2, P = 0.03). Treatment with eptinezumab also increased the number of headache-free days per month by 2.8 ± 0.5 days (P = 0.006). The mean number of abortive treatment days was reduced across the three-month period (from 11.9 ± 0.9 to 8.9 ± 0.5; t₉₉ = −2.7, P = 0.009). Compared to baseline, the reduction of mean HIT-6 score was 5.3 points at month 3 (from 69.4 ± 0.6 to 64.0 ± 0.4; t₉₃ = −5.3, P < 0.001).

At month 1, 2 and 3, 50% (N = 59), 53% (N = 63) and 53% (N = 63) of patients obtained at least a 30% reduction in MMD, respectively. The percentage of patients who achieved at least a 50% reduction in MMD at months 1, 2 and 3 were 36% (N = 43), 39% (N = 46) and 37% (N = 44), respectively (Fig. 3). Considering the average reduction in MMDs across the three months for the 119 patients, 61 (51%), 41 (35%) and 15 (13%) of patients achieved at least a 30%, 50% and 75% reduction in their mean migraine days, respectively. Thirty-six patients (30%) discontinued the treatment due to lack of efficacy (N = 30) or side effects (N = 6). One patient continued treatment at a local clinic and was discharge from our service.

Fig. 3.

Six-month outcomes on all patients treated with eptinezumab. P values are indicated in the graphs; *, P < 0.001

Twenty-one patients who achieved less than 30% reduction in MMD across the 3-month period but had some benefit either in migraine associated symptoms or in their HIT-6 scores were offered a second infusion.

Efficacy outcomes after second eptinezumab infusion – 6 months follow-up

A total of 82 patients received a second eptinezumab infusion. Of those, at the time of the analysis, 76 patients had their 6-month follow up review. Overall, during the entire 3-month observation period post-second eptinezumab infusion initiation, MMD, MHD and abortive intake days were significantly reduced compared to baseline. Additionally, the HIT-6 score was significantly reduced across the entire observational period (Fig. 3).

Compared to their baseline, the mean reduction in MMD over the three-month period following the second infusion of eptinezumab was 6.3 days (from 15.5 ± 1.0 at baseline to 9.2 ± 0.5; t₈₁= −6.7, P < 0.001). The mean reduction in MHD was 5.3 days (from 26.0 ± 0.8 at baseline to 20.8 ± 0.6; t₈₁= −3.1, P = 0.003). There was an increment of the number of headache-free days by 5.3 days (P < 0.001). The mean reduction in abortive treatment days was significant across the three-month period (from 12.8 ± 1.2 at baseline to 8.0 ± 0.6; t₈₁= −3.7, P < 0.001). Compared to baseline, the reduction of mean HIT-6 score at month 6 was 6.3 points from 68.9 ± 1.3 to 62.6 ± 0.7; t₇₃= −5.0, P < 0.001).

At month 4, 5 and 6, 66% (N = 50), 65% (N = 49) and 62% (N = 47) of patients obtained at least a 30% reduction in MMD, respectively. The percentage of patients who achieved at least a 50% reduction in MMD at months 4, 5 and 6 were 51% (N = 39), 50% (N = 38) and 41% (N = 31), respectively (Fig. 3). Considering the average reduction in MMD across the three months for the 76 patients, 48 (63%), 33 (43%) and 14 (18%) of patients achieved at least a 30%, 50% and 75% reduction, respectively, in their mean monthly migraine days.

Of the 21 patients who achieved less than 30% reduction in mean MMD across the 3-month period, and continued to have a second eptinezumab infusion, ten patients (48%) achieved at least a 30% reduction in mean MMD across the 3-month following the second eptinezumab treatment.

After the second infusion, 15 (20%) patients discontinued the treatment due to inefficacy, as there was no reduction in MMD across the three months (from 17.8 ± 0.5 at baseline to 16.7 ± 0.5 MMD across three months). Of these, 11 belong to the group who did not respond to the first infusion and continued to have the second one, hence four patients (5%) who responded to the first infusion, did not benefit from the second infusion.

The percentage of 30%, 50% and 75% responders across the six months of treatments, and the overall responder rates per 3-monthly periods and across all patients is shown in Fig. 4.

Fig. 4.

Percentage of 30%−50%−75% responders across the six months of treatments, and the overall responder rates across all patients

Effectiveness of IV eptinezumab in patients previously treated with one or more anti-CGRP pathway mAbs

Thirthy-two out of 80 patients who did not respond to at least one anti-CGRP pathway mAb (40%; 1 CGRP mAb failure: N = 21/80, 2 CGRP mAb failures: N = 11/80) achieved at least a 30% reduction in their mean MMD after the first eptinezumab infusion, and 26 (33%; 1 CGRP mAb failure: N = 18/80, 2 CGRP mAb failures: N = 8/80) of them continued to respond to eptinezumab after the second infusion. Of the CGRP mAbs naïve patients (N = 39/119), 29 patients (74%, all CM patients) achieved at least a 30% reduction in their mean MMD after the first eptinezumab infusion, and 22 patients (56%) continued to respond to eptinezumab after the second infusion. A chi-square test of independence was performed to examine the relation between CGRP naïve/prior CGRP failure and the 30% responder rate. The relation between these variables was significant, X² (1, N = 119) = 12.30, p = 0.0001. CGRP-naïve patients were more likely to achieve at least a 30% reduction of MMD than those who failed to respond to previous CGRP mAbs.

Effectiveness of IV eptinezumab in patients with chronic daily headache

Of the patients (50%) who reported a chronic daily headache pattern at baseline (Baseline MD: 19.9 ± 1.1; baseline HD: 30.0 ± 0.03), 24 (41%) and 18 (31%) achieved at least a 30% and 50% reduction in their mean MMD, correspondingly, after the first infusion of eptinezumab. Of the patients who did not have a daily headache pattern at baseline (baseline MD: 17.0 ± 1.0; baseline HD: 24.5 ± 0.5), 37 (62%) and 23 (38%) achieved at least a 30% and 50% reduction in their mean MMD, correspondingly, after the first infusion of eptinezumab. At six months, 22 (37%) and 17 (28%) of the CDH patients continue to have at least a 30% and 50% reduction in their mean MMD. Of the patients who did not have a daily headache pattern at baseline, 26 (43%) and 16 (26%) achieved at least a 30% and 50% reduction in their mean MMD, correspondingly, after the second infusion of eptinezumab. No association was found between the baseline headache pattern (daily/non-daily) and responders rate following the first or second eptinezumab infusion (p ≥ 0.18).

Safety and tolerability

After one infusion of Eptinezumab, 24 patients (20%) reported at least one adverse event. A total of 34 adverse events were reported by the patients after the first infusion. Nine patient reported at least one adverse events after the second infusion (Table 2). Adverse events were transient, lasting up to two weeks post-injection and described as mild or moderate. However, six patients (5%) discontinued the treatment because of side effects (cold/flu symptoms, raised blood pressure, which was found subsequently to be due to previously undiagnosed hypertension, atypical chest pain, headache worsening). The raised blood pressure was the only adverse event that occurred immediately after the eptinezumab infusion.

Table 2.

Percentage of adverse events after first and second eptinezumab infusions

	1 st infusion (N = 119) N (%)	2nd infusion (N = 76) N (%)
Flu/cold like symptoms	6 (5%)	5 (7%)
Dizziness	8 (7%)	1 (1%)
Fatigue/tiredness	5 (4%)	4 (5%)
Constipation	5 (4%)	0 (0%)
Migraine worsening	3 (3%)	0 (0%)
Widespread itchiness	2 (2%)	0 (0%)
Nausea	1 (1%)	0 (0%)
Cannula site reactions	1 (1%)	0 (0%)
Raised blood pressure	1 (1%)	0 (0%)
Atypical chest pain	1 (1%)	0 (0%)
Alopecia	1 (1%)	0 (0%)

N number

Discussion

This is a prospective 6-month single centre real-world analysis to evaluate the effectiveness of IV eptinezumab in a difficult-to-treat migraine population. The patients included in this analysis reflect the complex patients often seen in tertiary headache services. Almost half of the patients had a daily headache at baseline; patients were resistant to treatments having failed numerous preventive treatments including BoNTA. Furthermore, over 2/3 of the patients had failed at least one CGRP targeting therapies. It is well-known that sub-optimal response/lack of tolerability to available preventive medications, presence of multiple co-morbidities especially psychiatric, sleep-related, non-cephalic chronic pain, chronic fatigue and GI issues and the presence of a CDH pattern are factors that may impact negatively migraine treatment effectiveness [1, 16].

Treatment with Eptinezumab led to a meaningful benefit about half of our patients for the first three months. About 1/3 of patients were 50% responders and about 1/7 of patients were 75% responders. The treatment also led to a significant reduction in MHD, days with abortive treatment intake and HIT-6 and to an increment of headache-free days compared to baseline. After the second infusion at month 6, the percentage of patients who were 30% responders increased to about 2/3 of responders. The percentage of patients with 50% and 75% responders increased too, suggesting a sustained beneficial effect over six month of this therapy in both migraine symptoms and in migraine-related disability, as shown by the further reduction in the mean HIT-6 score at month 6. Our findings are less impressive than a recently published retrospective study, where almost 60% of the 100 patients enrolled obtained a 75% reduction in MMD [17]. It is likely that methodological differences coupled with the less treatment-resistant patient group included in that study, may explain the outcome differences compared to our results. A multicentre real-world prospective study conducted in 22 headache centres included a similar number of patients compared to our analysis (N = 74 patients) who were treated with eptinezumab for six months (EMBRACE II) [18]. Our efficacy outcomes were less favourable compared to this study. It is noteworthy that the diaries used in our audit discriminates between a MD, a HD and a background headache, whereas the diaries used in EMBRACE II only accounted for HD in the CM group. Furthermore, the patients included in our study and EMBRACE II have different degrees of complexities. Half of our patients had CDH at baseline and few patients only had EM. Additionally, the patients in our audit did not respond to an average of ten treatments at baseline compared to four treatments for the EMBRACE II study population; about 73% of our patients compared to 39% of the EMBRACE II study population had at least one of the commonest comorbidities present in migraine. Another interesting factor that may have played a role in the different treatment outcomes of our and the EMBRACE II studies maybe the use of 300 mg infusion in a subgroup of patients. Such a dose is not available in the UK at present. It is therefore plausible that the different headache diaries used and different patients included in the two studies may explain the different treatment outcomes. Overall the real-world data published so far including our experience, suggests that IV eptinezumab may have a treatment place in difficult-to-treat migraine, but also in treatment-resistant migraine patients with several comorbidities and chronic daily headache patterns.

In view of the extreme complexity of the migraine patients included in this audit, some patients with a borderline response (< 30% reduction in MMD) to the first infusion, were given the opportunity to continue the treatment with a second infusion. About half of these patients obtained a favourable response after the second infusion. This phenomenon was already observed in the real-world studies conducted with erenumab, where a percentage of non-responders to the first 3 months of treatments, became responders when the treatment was continued [19, 20]. It has also been shown that some patients treated with CGRP targeting therapies display a delay response at six months [21]. For these reasons, our data in this small subgroup indicates that in the complex migraine population, instead of switching eptinezumab to a different CGRP targeting therapy, it may be worth considering extending the treatment period by another three months.

Real-world evidence has suggested that patients with CDH may respond less meaningfully to anti-CGRP mAbs. A clinical study conducted on 32 patients with CDH treated with anti-CGRP mAbs for three months, showed a lower than expected 50% response rate (25%) [22]. Subsequently, a multicentre cohort study evaluating the efficacy of galcanezumab and fremanezumab in a difficult to treat cohort of migraine patients, showed that a statistically significant smaller percentage of CDH patients responded to the treatments compared to the non-CDH migraine group (43% vs. 64%) [23]. Similarly, our 30% and 50% response rates were lower in the CDH cohort compared to the non-CDH cohort, however the differences were not statistically significant. Methodologically robust studies are needed to clarify this clinical issue. In clinical practice, we often end up offering a prolonged trial of a CGRP targeting therapies (6 months) in these patients as well as combinations of a CGRP targeting therapy with either an oral prophylactic agent or an injectable one (Bonta or greater occipital nerve blocks).

There is paucity of evidence helping clinicians in treatment decision making when patients do not respond to the first and second anti-CGRP mAbs. Switching from a mAb targeting the CGRP receptor to an anti-CGRP mAb targeting the ligand has shown to be effective in about 30–40% of patients [24, 25]. There is some initial retrospective data showing that eptinezumab may be effective in a small percentage of migraine patients who had a suboptimal response to both erenumab and either galcanezumab and fremanezumab [26]. The majority of our patients failed one or two CGRP targeting therapy by the time they tried IV eptinezumab. Despite this, 40% of patients at 3 months and 33% at 6 months responded to eptinezumab as per NICE criteria, suggesting that eptinezumab may offer high chances to improvement if tried as the first CGRP targeting therapy (responders: 74%), but it may also be a reasonable treatment option in patients who did not respond to one or two CGRP targeting therapies.

IV eptinezumab was well tolerated in our experience. However, the number of our patients experiencing adverse events was much higher compared to those reported in recent real-world studies, where only a few patients, even at the dose of 300 mg quarterly, experienced side effects [17, 18]. It is noteworthy that our patients had several comorbidities and perhaps this may have played a role in developing side effects compared to other patient groups [16].

The main limitation of real-world studies is the open label design. However, our cohort of patients had a long history of CM with or without a CDH pattern and they were treatment-refractory, hence it is unlikely that the improvement in responders was due to placebo alone. It is noteworthy that the anti-CGRP mAbs clinical trials body of evidence has highlighted an inverse correlation between the number of treatment failed by patients and the size of placebo, further supporting a biological effect of eptinezumab in our responders rather than a placebo effect [27, 28].

In conclusion, eptinezumab seems to be an effective and well tolerated treatment in otherwise treatment-refractory migraine patients with or without a chronic daily headache pattern and with multiple co-morbidities. Responders report a sustained improvement to two infusions with a proportion of patients experiencing a beneficial accumulative effect. Delayed responders may benefit from a second infusion before the eptinezumab is discontinued. Eptinezumab could be offered as a treatment option in refractory patients who had a suboptimal response to one or two anti-CGRP pathway mAbs, though our data suggest to consider this treatment earlier on in the naïve to CGRP targeting treatments population, in view of the significantly higher percentage of responders in the latter group.

Authors’ contributions

AA conceived the study and supervised the project. She performed the statistical analysis, analysed the data, drafted the initial manuscript.RAR collected the data, helped with data analysis.BH, MM and IS managed the intravenous eptinezumab service, collected the audit tools outcome (headache diaries and HIT-6 scores) analysed some of the results and drafted the initial manuscript.GL, JB and RK treated all the patients included. JB and RK also interpreted the results and drafted the initial manuscript.GL conceived the study and supervised the project. He interpreted the results. He also drafted the manuscript.All authors reviewed the manuscript for content, and approved the final version of the manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

APA received speakers’ honoraria by Abbvie, Pfizer, Teva; research support to institution by Brain Research UK; Medical Research Council; Abbvie; Pfizer; advisory board of Neuresta INC; relationship with scientific journals: Editorial Board Cephalalgia; ToxinsSociety Leadership/Board position: Trustee of the International Headache Society; Chair Headache SIG of British Pain Society; Lead of the National Audit for Headache Disorders/National Audit of Migraine, UK.BH: received speakers/advisory board’s honoraria from TEVA, Organon, Lundbeck, Pfizer, Abbvie, eNeura.RAR, MM, IS have nothing to declare.JB: received speaker/advisory board’s honoraria from TEVA and PfizerRK: received speaker’s honoraria from Abbvie and Pfizer and personal fees from TEVA GL : he is the Co-Chair of the Medical Advisory Board of the Trigeminal Neuralgia and facial Pain Charity (TNA) UK; he received speaker’s honoraria from Pfizer, Teva, Eli Lilly, Lundbeck, Dr Reddy’s laboratories; he served on the advisory boards of Pfizer, Teva, Eli Lilly, Lundbeck, Dr Reddy’s laboratories’; he participated in clinical trials as principal investigator for Novartis, Eli Lilly, Teva, Noema.