I-GRAINE, the Italian Registry for the treatment of migraines
Elena Bosani new president of Égalité onlus
13 May 2022
Harmful practices towards women. Consultation in the EU
21 May 2022
The I-GRAINE national register on patients suffering from migraine has been implemented in Italy, to remedy the lack of data on the conditions and development status of this disabling disease in the population.
In this way, it is possible to acquire precise information for each individual patient, necessary to evaluate the effectiveness of the treatments adopted and, at the same time, to optimize the resources of the National Health System to best treat the largest possible number of people.
Headaches and migraines
Headache is the scientific term with which headache is identified, made up of numerous categories and sub-categories that are difficult to manage in such a way as to lead to a complete eradication of the problem.
They are distinguished in primary and secondary headaches and migraine (part of the first category) it is divided in turn into migraine without aura and migraine with aura. (1)
The causes of migraine
A study recently published has finally demonstrated the cause of migraine pain, due to Schwann cells (a sheath that surrounds the nerves) solicited by the calcitonin gene-related peptide (CGRP), which induces hypersensitivity (allodynia) and stimulation of nociceptors.
The use of CGRP antagonists (e.g. monoclonal antibodies) in nanoencapsulated form appears to be more promising in reducing headache pain. (2)
Consult with experts
On the occasion of the 9th National Headache Day (15-XNUMX May), the Italian Society for the Study of Headaches (SISC) organized an initiative called 'Let's face it'.
All they had the opportunity to make a short video to which the experts of the SISC and the Italian Society of Neurology (SIN) replied on their respective channels social (available at any time). (3)
I-GRAINE register
The I-GRAINE register (Italian miGRAINe rEgistry) was organized and developed by the San Raffaele University of Rome, with the aim of systematically collecting data on migraine patients through the various participating headache centers and clinics in Italy (about 40).
The register it will be "accompanied" by the trial of Rimegepant, an anti-CGRP approved by EMA with double effect (prophylaxis and acute phase) for children and adults with at least four attacks per month. (4)
A five-year study
It has been implemented as a prospective, non-interventional observational study lasting 5 years, based on the data collected by the IRON project.
Through sub-studies retrospective, prospective and longitudinal, there is the intention to analyze in detail the clinical history of patients, before and during the first two years from the start of treatment at the headache center / clinic. (5)
The IRON project
The IRON project (Italian chROnic migraine) was the first registry developed for the monitoring of chronic migraines, launched on 1 May 2018 by 28 Italian headache centers.
Patients have been subjected to screening methods through individual interviews, using a online database which included 6 domains which included: (6)
- lifestyle, behavioral and socio-demographic factors,
- characteristics of migraine before becoming chronic,
- characteristics and comorbidities of chronic migraine,
- resources used for treatment and socio-economic benefits derived,
- MIDAS questionnaire (Migraine Disability Assessment Score Questionnaire),
- HIT-6 questionnaire.
The effectiveness of IRON and the results achieved led to the development of its heir I-GRAINE.
RICe register
The Italian Register of Headaches RICe carried out by the SISC has also started from 1 April 2019 to define the clinical characteristics and the diagnostic and therapeutic path of patients suffering from headaches, who come to the Italian Headache Centers, as well as identify the prevalence of primary and secondary headaches, in the form of prospective observational study without an established specific duration. (7)
The effect Migraine Intensity Quarantine was assessed through this registry, using information on migraine characteristics, lifestyles, emotions, professional status infectious and perception of COVID-19 in the 2 months before quarantine and after its onset.
The impact of Covid-19 on migraines
In the 433 subjects There was an improvement related to the number of days they stayed at home, with the exception of those who had adverse feelings about the situation, which was matched by an increase in migraine intensity. (8)
A later study was traced back starting from the same subjects, reduced to 304, comparing the pre-pandemic, the first and the second pandemic. In the latter case, the frequency and intensity of migraines, and medication intake has worsened, showing how the prolongation of the pandemic has led to a negative emotional perception, which has affected the professional status of migraine in Italians. (9)
Migraine 2022 Project
The 2022 Migraine Project, edited by Motor Health, has placed great emphasis on the therapies currently available and on the benefits of the latest innovations, such as monoclonal anti-CGRP antibodies, whose main limit is due to the availability and costs for the NHS, which led to the establishment of the prescriptive limits by AIFA, namely: (10)
- > 8 migraine days / month,
- > 3 failures of prophylaxis,
- marked disability (MIDAS> 11),
- effectiveness check after 3 months (limiting for those who have positive responses in later times).
New drugs
Other new drugs in the home straight are:
Ditani: drugs able to interrupt the migraine attack without vasoconstriction and usable by patients with cardiovascular attacks, without limits for over 65
gepanti: action similar to monoclonal antibodies, taken orally and with therapeutic as well as preventive action.
They were also introduced the results of the Survey 'Access to Care III' conducted by European Migraine & Headache Alliance (EHMA), which collaborated on Progetto Micrania 2022, to understand the state of access to care in Europe.
The main conclusions reported for Italy are:
- 58% reported suffering from chronic migraine, of severe intensity and for very long periods, with severe influence on daily activities,
- the General Practitioner is the main specialist, followed by the neurologist, but 22% declared that they are not followed by any professional figure,
- the main treatments are triptans (74%) and botulinum (5%), with long times between diagnosis and treatment,
- Botox and anti-CGRP monoclonal antibodies are the most difficult to access treatments, because they are not covered by private insurance or the NHS, and also due to the limited quantities available.
Migraine, a gender disease
Migraine it is a disease that mainly affects women, so much so that out of 6 million people who suffer from it, 4 are women (2/3). The consequences are much more deleterious for work and social and private life, as women are affected in the most fertile phase and many symptoms (e.g. pain, discomfort with light and noise, nausea) are significantly more linked to migraines. than men.
At the expense of men on the other hand, the higher costs for management and treatment for migraines and higher productivity losses at work were identified. (11)
'United against migraine'
The Onda Foundation, active in the protection of women's health and gender, has promoted an awareness campaign.
Through his' Manifesto: United against migraine 'wanted to underline the importance of promoting awareness of women and people affected by migraines and increasing interventions and collaborations between professionals in the sector, to improve the effectiveness of treatments, which should have simplified access. (12)
Social invalidity, the first in Europe
Law 81/2020 decreed a chronic primary headache, ascertained for at least one year in the patient following a diagnosis by a specialist as disabling, as a social disease. Headaches are as follows (13):
- chronic and high frequency migraine,
- chronic daily headache with or without excessive use of analgesic drugs,
- chronic cluster headache,
- chronic paroxysmal migraine,
- unilateral neuralgiform headache of short duration with ocular redness and tearing,
- continuous migraine.
An unenforced law
Immediate complications, however, seem to intervene in the correct application of the law, which within 180 days of its entry into force should have identified projects aimed at experimenting innovative methods of taking care of people with headaches and the criteria and methods of implementation of the projects by the Regions, considered instead already implemented according to a question to the Chamber by the Hon. Fabiola Bologna to Undersecretary Andrea Costa. (14)
Waiting for clarification on the implementation of the law, the TELL-Migraine project proposes to devise a support system for patients along the patient journey, to support them in the help they need and avoid potentially harmful do-it-yourself therapies and increase headache culture among patients, the general public and healthcare institutions. (15)
Provisional conclusions
Headaches and migraines in particular they are incapacitating and underestimated diseases, which lead the affected subjects to abandon possible attempts at treatment. The implementation of the I-GRAINE register and other initiatives are a novelty that lead to the presupposition of important changes in this paradigm.
The implementation of laws dedicated is a first step, which however must continue along a path that leads to interventions and concrete actions to encourage care and services for subjects suffering from migraines and other forms of headache. At present, there are several associations that patients can refer to, as suggested by the Italian Neurological Association for Headache Research (ANIRCEF). (16)
Dario Dongo and Andrea Adelmo Della Penna
Note
(1) Andrea Adelmo Della Penna. Monoclonal antibodies for the treatment of migraine, conference by the Turin Academy of Medicine. Egalite, 8.5.21, https://www.egalite.org/anticorpi-monoclonali-per-il-trattamento-dellemicrania-convegno-dallaccademia-di-medicina-di-torino/
(2) DeLogu et al. (2022). Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice. Nature Communications 13: 646, https://doi.org/10.1038/s41467-022-28204-z
(3) Italian Society for the Study of Headaches. XIV National Headache Day. https://www.sisc.it/ita/giornata-nazionale-del-mal-di-testa-covid_8/mal-di-testa-cefalee-emicrania-mettiamoci-la-faccia_14.html (site visited on 15.5.22)
(4) IRCCS San Raffaele. IRCCS San Raffaele / Prof. Barbanti: "From peptide to monoclonals through the migraine register up to Rimegepant, today the war against headaches can be won". 09.05.22,https://www.sanraffaele.it/comunicazione/news/12603/irccs-san-raffaele-prof-barbanti-dal-peptide-ai-monoclonali-passando-per-il-registro-dell-emicrania-sino-ad-arrivare-al-rimegepant-oggi-la-guerra-al-mal-di-testa-si-puo-vincere (site visited on 16.5.22)
(5) See http://www.i-graine.it/
(5) Barbanti et al. (2018). The Italian chROnic migraiNe (IRON) Registry: first report from 28 headache centres. In: 12th European Headache Federation Congress jointly with 32nd National Congress of the Italian Society for the Study of Headaches. The Journal of Headache and Pain 19 (Suppl 1): 80, https://doi.org/10.1186/s10194-018-0900-0
(6) Italian Society for the Study of Headaches. Italian Register of Headaches (RICe Study) - Synopsis. https://www.sisc.it/upload/19.02.03_V1_RICe_Sinossi-1562049786323-18471.pdf
(7) Delussi et al. (2020). Investigating the Effects of COVID-19 Quarantine in Migraine: An Observational Cross-Sectional Study From the Italian National Headache Registry (RICe). Front. Neurol. 11: 597881, https://doi.org/10.3389/fneur.2020.597881
(8) Gentile et al. (2021). Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort. Brain Sciences 11: 482, https://doi.org/10.3390/brainsci11040482
(9) Healthcare Engine. Migraine 2022 Project. https://www.motoresanita.it/wordpress/wp-content/uploads/2022/04/DOCUMENTO-DI-SINTESI-Progetto-Emicrania-2022-16-marzo-2022.pdf
(10) National Institute of Health (2018). Migraine: A Gender Disease - Socio-economic Impact in Italy. ISBN 978-88-0632-2
(11) Onda Foundation (2022). Migraine: A Gender Pathology - Manifesto for Collective Commitment. https://ondaosservatorio.it/ondauploads/2022/03/Emicrania-una-patologia-di-genere-1.pdf
(12) President of the Republic. Law 14 July 2020, n. 81 - Provisions for the recognition of chronic primary headache as a social disease. GU General Series n. 188 of 28-07-2020, https://www.gazzettaufficiale.it/eli/id/2020/07/28/20G00100/sg
(13) Chamber Act. Question for immediate answer in the Commission 5/07755. https://aic.camera.it/aic/scheda.html?core=aic&numero=5/07755&ramo=CAMERA&leg=18 (site visited on 15.5.22)
(14) Luigi Vanvitelli University of Campania. TELL-Migraine research project. https://www.pubblicazioni.unicampania.it/data/2022/_dipartimento_scienze_mediche_chirurgiche_avanzate/DSMC_13307_all.2_progetto_tell_migraine_protocollato.pdf
(15) ANIRCEF. Patient associations. https://www.anircef.it/2019/01/27/associazioni-per-pazienti/ (site visited on 15.5.22)
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in Food Technology and Biotechnology, licensed food technologist, he follows the research and development area of Wiise Srl, a benefit company.
