Background
Clinical trials have shown the safety and clinical superiority of erenumab compared to placebo in chronic migraine (CM). The aim of this analysis is to evaluate the effectiveness and ...tolerability of erenumab in a real-world setting in patients with refractory CM.
Methods
This is a prospective single centre real-world audit conducted in patients with CM with and without medication overuse, refractory to established preventive medications, who received monthly erenumab for 6 months.
Results
Of 164 patients treated, 162 patients (female = 135, mean age 46 ± 14.3 years old) were included in the audit. Patients had failed a mean of 8.4 preventive treatments at baseline and 91% of patients failed Botulinum toxin type A at baseline. The mean reduction in monthly migraine days was 6.0 days at month 3 (
P
= 0.002) and 7.5 days at month 6 (
P
< 0.001) compared to baseline. The mean reduction in monthly headache days was 6.3 days (
P
< 0.001) at month 3 and 6.8 days (
P
< 0.001) at month 6. At month 3, 49%, 35% and 13% and at month 6, 60%, 38% and 22% of patients obtained at least a 30%, 50% and 75% reduction in migraine days, respectively. The percentage of patients with medication overuse was reduced from 54% at baseline to 20% at month 3 and to 25% at month 6. Compared to baseline, the mean reduction of Headache Impact Test-6 score was 7.7 points at month 3 (from 67.6 ± 0.4 to 59.9 ± 0.9) (
P
< 0.001) and of 7.5 points at month 6 (60.1 ± 1.3) (
P
= 0.01). The percentage of patients with severe headache-related disability (HIT-6: 60–78) was reduced from 96% at baseline to 68% after three monthly treatments and to 59% after six treatments. At least one side effect was reported by 48% of patients at month 1, 22% at month 3 and 15% at month 6. Constipation (20%) and cold/flu-like symptoms (15%) were the most frequent adverse events reported.
Conclusion
Erenumab may be an effective and well tolerated therapy for medically refractory CM patients with and without medication overuse.
Background
Health-related quality of life (HRQoL) is emerging as an important element of clinical research in primary headache disorders, allowing a measure of the impact of headache on patients’ ...well-being and daily life. A better understanding of this may contribute to improved resource allocations and treatment approaches.
Objective
The objective of this study is to review available data on HRQoL in primary headache disorders and identify any influencing factors.
Methods
Database searches including MEDLINE, PsycINFO and EMBASE were performed. Studies that investigated HRQoL in patients with primary headache disorders were included and reviewed. Trials that evaluated the efficacy of medications or interventions were excluded.
Results
A total of 80 articles were included in the review. Both physical and emotional/mental aspects of HRQoL were impaired across headache subtypes, although the extent varied depending on headache type. A number of factors influencing HRQoL were also identified.
Conclusion
This narrative review suggests that headache, particularly in its chronic form, has a great impact on HRQoL. Clinical practice should not solely focus on pain alleviation but rather adopt routine assessment of HRQoL. Furthermore, identification and management of associated psychological comorbidities, which can significantly influence HRQoL in headache sufferers, are essential for optimal clinical management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of ...the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.
Background
Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year ...sustained effectiveness of CGRP MABs in resistant chronic migraine (CM) is sparse.
Methods
This is a two-year real-world prospective analysis of an ongoing single centre audit conducted in patients with resistant CM. Patients received monthly erenumab for six months before assessing its effectiveness. Responders were considered those who achieved at least 30% reduction in monthly migraine days (MMD) by month 6, compared to baseline. Secondary outcomes were also analysed, including changes of the Headache Impact Test version 6 (HIT-6).
Results
One hundred sixty-four patients 135 (82.3%) females; mean age 46 SD 14) years were included in the audit and 160 patients analysed. Patients had failed a mean of 8.4 preventive treatments at baseline. At month 6, 76 patients (48%) were 30% responders to erenumab, 50 patients (31%) were 50% responders and 25 (15%) were 75% responders. The mean reduction in MMD at month 6 was 7.5 days compared to baseline (
P
< 0.001). At month 12 and month 18, 61 patients (38%) and 52 patients (33%) remained 30% responders respectively. At month 24, 36 patients (23%) remained 30% responders, 25 patients (16%) and 13 patients (8%) were respectively 50% and 75% responders. Compared to 95% of patients at baseline, at months 6, 12 and 24, 46%, 29% and 16% of responders respectively had severe disability. At least one adverse event at month 6, 12, 18 and 24 was reported by 49%, 19%, 11% and 3% of patients. By month 6, 13% of patients discontinued the treatment because of side effects, often constipation.
Conclusions
Long-term sustained effectiveness of erenumab was reported only by a minority of resistant CM patients. Although more research in resistant migraine is needed, Erenumab can provide long-term meaningful reduction in migraine load and migraine-related disability in some patients.
Background
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or with autonomic symptoms (SUNA) are grouped together within the trigeminal ...autonomic cephalalgias (TACs). However, the SUNCT and SUNA phenotype and management overlap with those of trigeminal neuralgia (TN). Additionally, a broad variety of cerebral pathologies are reportedly able to trigger either TN- or SUNCT-like pain, and emerging structural neuroimaging findings suggest the possible role of neurovascular conflict with the trigeminal nerve in SUNCT, further supporting aetiological and pathophysiological overlaps among SUNCT, SUNA and TN.
Case report
We present the first case of coexisting chronic SUNCT- and TN-like phenotypes caused by haemorrhagic infarct of the dorsolateral medulla.
Discussion
In light of our case, a perturbation of the dorsolateral medullary circuits may constitute an important pathophysiological component, supporting a unifying nosological hypothesis that considers SUNCT, SUNA and TN clinical variants of the same disorder.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Single-pulse transcranial magnetic stimulation (sTMS) of the occipital cortex is an effective migraine treatment. However, its mechanism of action and cortical effects of sTMS in migraine are yet to ...be elucidated. Using calcium imaging and GCaMP-expressing mice, sTMS did not depolarise neurons and had no effect on vascular tone. Pre-treatment with sTMS, however, significantly affected some characteristics of the cortical spreading depression (CSD) wave, the correlate of migraine aura. sTMS inhibited spontaneous neuronal firing in the visual cortex in a dose-dependent manner and attenuated
l
-glutamate-evoked firing, but not in the presence of GABA
A/B
antagonists. In the CSD model, sTMS increased the CSD electrical threshold, but not in the presence of GABA
A/B
antagonists. We first report here that sTMS at intensities similar to those used in the treatment of migraine, unlike traditional sTMS applied in other neurological fields, does not excite cortical neurons but it reduces spontaneous cortical neuronal activity and suppresses the migraine aura biological substrate, potentially by interacting with GABAergic circuits.
Background
The multinational phase 3b DELIVER trial was designed to evaluate the efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures across ...17 countries. In the placebo-controlled portion, eptinezumab relative to placebo demonstrated greater reductions in migraine and headache frequency, migraine and headache severity, and acute medication use. The objective of this report is to describe the effects of eptinezumab on self-reported work productivity in the placebo-controlled portion of DELIVER.
Methods
Adults 18–75 years of age with migraine and documented evidence of 2 to 4 prior preventive treatment failures in the past 10 years were randomized to receive eptinezumab 100 mg, 300 mg, or placebo intravenously (IV) every 12 weeks. The Work Productivity and Activity Impairment questionnaire specific to migraine (WPAI:M), which comprises 6 items (4 of which are completed by currently employed patients only), was administered every 4 weeks. Changes from baseline in subscores (absenteeism, presenteeism, work productivity loss, and activity impairment) were calculated based on item responses. A mixed model for repeated measures was used to analyze changes from baseline in WPAI:M subscores.
Results
A total of 890 adults (mean age, 43.8 years) were included in the full analysis set (eptinezumab 100 mg,
n
= 299; eptinezumab 300 mg,
n
= 293; placebo,
n
= 298). Mean WPAI:M subscores at baseline indicated a negative impact of migraine attacks on work productivity and ability to complete normal daily activities. Eptinezumab improved WPAI:M subscores more than placebo at all assessment points throughout the study. Mean changes from baseline in self-reported work productivity loss were −19.5, −24.0, and −9.7 at Week 12; and −22.6, −20.2, and −7.2 at Week 24 (all
P
< 0.001 vs placebo) for eptinezumab 100 mg, eptinezumab 300 mg, and placebo, respectively. Mean changes from baseline in activity impairment were −21.3, −23.8, and −11.2 at Week 12; and −24.7, −22.6, and −10.1 at Week 24 (all
P
< 0.0001 vs placebo). Similarly, mean improvements in absenteeism and presenteeism were greater in the eptinezumab groups than in the groups receiving placebo at all timepoints (
P
< 0.05).
Conclusion
In adults with migraine and prior preventive treatment failure, eptinezumab 100 mg and 300 mg IV every 12 weeks improved absenteeism, presenteeism, work productivity loss, and activity impairment more than placebo.
Trial registration
ClinicalTrials.gov
(Identifier:
NCT04418765
); EudraCT (Identifier: 2019–004497-25) (
https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004497-25/PL
).
Graphical Abstract
Eptinezumab improves self-reported work productivity in patients with migraine and prior preventive treatment failures.
With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for ...migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene–related peptide–targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain—binary toxin-AA (BiTox/AA)—cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.
The red ear syndrome Lambru, Giorgio; Miller, Sarah; Matharu, Manjit S
Journal of headache and pain,
10/2013, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Red Ear Syndrome (RES) is a very rare disorder, with approximately 100 published cases in the medical literature. Red ear (RE) episodes are characterised by unilateral or bilateral attacks of ...paroxysmal burning sensations and reddening of the external ear. The duration of these episodes ranges from a few seconds to several hours. The attacks occur with a frequency ranging from several a day to a few per year. Episodes can occur spontaneously or be triggered, most frequently by rubbing or touching the ear, heat or cold, chewing, brushing of the hair, neck movements or exertion. Early-onset idiopathic RES seems to be associated with migraine, whereas late-onset idiopathic forms have been reported in association with trigeminal autonomic cephalalgias (TACs). Secondary forms of RES occur with upper cervical spine disorders or temporo-mandibular joint dysfunction. RES is regarded refractory to medical treatments, although some migraine preventative treatments have shown moderate benefit mainly in patients with migraine-related attacks. The pathophysiology of RES is still unclear but several hypotheses involving peripheral or central nervous system mechanisms have been proposed.
Primary headache disorders that are more frequently encountered in the paediatric population include migraine and tension-type headaches. The trigeminal autonomic cephalalgias (TACs), which includes ...cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), are rarely reported in the paediatric population. The 1-year prevalence of CH seems to be 0.03 %. The clinical features of childhood and adolescence onset CH seem to be similar to those of adult onset. Cranial autonomic features and restlessness seem to less prominent in children than in adults. When restlessness is present, it often manifests as thrashing around in children and can distract attention from the headache, thereby contributing to a delay in diagnosis. The frequency of cluster periods seems to be lower in childhood. Similarly, the duration of the single cluster period seems to be shorter. The temporal pattern shows a trend towards a gradual increase of frequency and duration of symptoms in adult life. In terms of management of paediatric CH, oxygen has been used successfully in several paediatric CH patients, and given its good side-effect profile, it is considered the abortive agent of choice for paediatric CH. Verapamil is the preventative drug of choice in both episodic and chronic CH, though paediatric patients should be started on lower doses and titrated according to age. Paediatric-onset PH and SUNCT are very rarely reported. The clinical phenotype and response to treatment seem to resemble the adult-onset form. Paediatric-onset TACs are poorly recognized and there is often a delay of several months or years before the diagnosis is made. Awareness of typical clinical pictures of these excruciating headaches is essential to allow prompt initiation of the appropriate management.
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