Los resultados del consenso para el tratamiento de la prevención de la migraña entre las especialidades de neurología y farmacia hospitalaria, indican un entorno general de sinergia entre neurólogos y farmacéuticos hospitalarios.

A nivel de práctica clínica, los resultados confirman como opción terapéutica para pacientes con migraña refractaria, el uso de fármacos con diferentes mecanismos de acción de forma simultánea, como ocurre en el uso de AMC con oros fármacos biológicos. Además, los resultados del consenso indican que se debe valorar la retirada temporal tras un año de tratamiento cuando el paciente alcanza una buena respuesta, haciendo seguimiento por si fuera necesario reinstaurarlo.

Referente a la relación médico-paciente, los resultados del consenso indican que una correcta educación sanitaria sobre el manejo y conservación del AMC, así como informar al paciente de los posibles efectos adversos y/o complicaciones, y estableciendo las visitas de seguimiento, mejoran la calidad de vida de los pacientes y la adherencia al tratamiento.

The low effectiveness and tolerability of current oral preventive treatments for migraine has prompted the search for new therapeutic strategies, leading to the development of monoclonal antibodies (MCAs) that specifically target the calcitonin gene-related peptide (CGRP)—which is of relevance in the pathophysiology of migraine—or its receptor (anti-CGRP MCAs)1.

Clinical trials and real-world studies have demonstrated the safety and effectiveness of anti-CGRP MCAs. They do not cross the blood–brain barrier, thus avoiding adverse events in the central nervous system, there is no risk of drug interactions compared to traditional preventive treatments as they are not metabolised in the liver, they initiate their response within a few weeks of starting treatment, and they have excellent tolerability. Their effectiveness has also been demonstrated in episodic and chronic migraine as measured using objective and subjective parameters2.

Although there are few reports on anaphylactic reactions, anti-CGRP MCAs are contraindicated in patients with hypersensitivity to the active ingredient; furthermore, their long-term safety remains unknown in patients with a history of cardiovascular disease or at cardiovascular risk, and in patients more than 65 years. As a precautionary measure, they should not be used in pregnant women3,4.

The following anti-CGRP MCAs have demonstrated effectiveness in chronic and episodic migraine: eptinezumab (not yet marketed in Spain), galcanezumab, fremanezumab, and erenumab5–8. These drugs are reimbursed by the Spanish public healthcare service for the preventive treatment of patients with high-frequency episodic migraine (8–14 migraine days/month) and in patients with chronic migraine after the failure of 3 preventive treatments (including botulinum toxin in patients with chronic migraine) used at the appropriate doses and for a minimum of 3 months.

Consensus among multidisciplinary teams on the treatment of migraine patients could facilitate progress in the management of these drugs and achieve the best health outcomes.

Thus, this consensus document had the following objectives: to determine the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP MCAs in the treatment of migraine; to identify remaining controversies; to propose consensus recommendations for the improvement of care; and to promote access by clinicians and patients to these new treatments for the prevention of migraine with biological drugs in order to improve patient care and follow-up.

Firstly, a scientific committee (SC) was set up comprising 4 hospital pharmacists and 4 neurologists with expertise in migraine. The SC reviewed the most recent literature on migraine treatment and proposed 88 statements grouped into 3 modules: clinical aspects in the management of biological treatments; strategies for patient education and improved adherence; and coordination to improve workflow.

The SC then selected an initial panel of 62 neurologists and hospital pharmacists with recognised experience in the management and follow-up of migraine patients; however, due to professional commitments on the part of 3 of the panellists, the second round included 59 participants.

Technical and methodological support was provided by the technical-scientific team of the Luzán 5 Health Consulting Research Unit.

The Delphi method was used to identify consensus or otherwise on the proposed statements. This method is a structured communication technique which, through the guidance and supervision of the coordinators and without the need for physical presence, allows a large group of experts to obtain a solution to a complex problem in clinical practice or one with little evidence9–11.

Based on this method, the panellists were sent a questionnaire on which they could show their degree of agreement with the statements on a single 9-point Likert-type ordinal scale structured into 3 groups according to the level of agreement-disagreement. A score of 1–3 represented no consensus, 4–6 represented inconclusive, and 7–9 represented consensus. Statements without sufficient consensus were subjected to a second round. The results were obtained over a period of 4 months and all communication was conducted via email and the Delphi platform.

Finally, the SC met to discuss and analyse the results. They defined each statement as follows: there was consensus when two-thirds or more (≥66.66%) scored within the ranges 1–3 or 7–9; no consensus when one-third or more (≥33.33%) scored within the 1–3 range and another third in the 7–9 range; and inconclusive when the median score was within the 4–6 range12.

As shown in Fig. 1, after two rounds of consultation, consensus of agreement was reached on 71 out of 88 statements (80.7%) and consensus of disagreement on one statement (1.1%); 16 statements (18.2%) remained inconclusive. Tables 1, 2, and 3 show the scores and degree of agreement by module.

Fig. 1.

Flowchart of the Delphi method used to reach consensus and results.

(0,29MB).

The Delphi technique is a consensus method enabling a panel of experts to make decisions in situations of uncertainty; their opinions can assist in generating ideas or guidelines, developing recommendations, or defining indicators or clinically significant interactions12–16.

Although expert consensus should be considered at the lower level in the evidence pyramid, its strength lies both in the inputs available to the experts (systematic reviews, experiments, personal experience, and qualitative studies) and in the methods used to reach consensus16. The high degree of consensus reached, which was over 80%, together with initiatives such as the publication of the White Paper on migraine in Spain, or the NEXOS Neurology multidisciplinary conference, show a general environment of synergy between neurologists and hospital pharmacists and represents a starting point for establishing a practical basis for their implementation in real practice, recording the real-world results of MCA treatment, or including pharmacists in headache units17,18.

During the above-mentioned conference, it became clear that the available oral preventive drugs are associated with an insufficient response, whereas anti-CGRP MCAs have high selectivity, that access to the new drugs and education in their administration should be facilitated, and that the creation of a working group between the two services for a better approach to migraine patients should be encouraged.

The Spanish Society of Neurology (SEN) Clinical Practice Manual on Headache recommends the simultaneous use of drugs with different mechanisms of action as a therapeutic option for patients with refractory migraine19; the results of our study are in line with this recommendation. Specifically, the concomitant use of MCAs with other biological drugs should be considered on a case-by-case basis, the discontinuation of preventive treatment before initiating MCA treatment is not needed when there is a partial response, a different MCA should be used when no response has been obtained with the first one given that up to 30% of initially non-responsive patients may benefit from a change in an MCA drug, and at least 3 months should elapse before assessing its effectiveness by evaluating the reduction in the number of days with migraine, but without taking into account its intensity, as some studies have done20.

The study by Briceño-Casado et al.21 compared the effectiveness and safety of three anti-CGRP MCAs. They found that the drugs could be considered equivalent therapeutic alternatives and that their use would facilitate the sustainability of healthcare systems through price competition.

Consensus was reached on temporary discontinuation after 1 year of treatment in patients with a good response, with follow-up in case another period of treatment is needed, and in patients without a reduction in migraine days in the range of 30%–50% after 12 weeks, thus following recommendations for rational drug use22.

Adherence is the basis of treatment success, which can be improved by making patients aware of the expected results, educating them in how to follow instructions for administration and the management of MCA storage, informing them possible adverse effects and/or complications, providing them with tools for identifying non-adherence, providing timely and specialised professional contact, and encouraging the use of a headache diary, since health education improves the quality of life of patients23. A study conducted in Spain found that around 30% of patients with migraine receiving prophylaxis maintained their treatment at 6 months and 12 months24. It is also essential to conduct follow-up visits, which include assessing effectiveness and safety using objective parameters, ensuring the correct mode of administration, and reviewing the occurrence of adverse events and their correct management. These aspects require tools for documenting pharmaceutical care, such as the Pharmacists' Care of Migraineurs Scale (PCMS), which was proposed by Skomo25,26.

The White Paper on Migraine in Spain identifies hospital pharmacy as an involved agent, especially in relation to the validation of the prescription and dispensing of anti-CGRP monoclonal antibodies17.

The role of the Pharmacy and Therapeutics Committee in the selection of MCAs included in the Pharmacotherapeutic Guidelines could affect the availability of all MCAs and the choice of treatment, and could have influenced the apparent disagreement over the responsibility of hospital pharmacists in the final choice of treatment.

The findings, comments, and conclusions of this work are those of the authors and are therefore the sole responsibility of the authors. This article may mention therapeutic options that refer to indications, dosages, and/or forms of administration of products that are not currently authorised in Spain. We emphasise that any drug mentioned must be used in accordance with the technical data sheet currently in force in Spain.

None declared.