Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry.

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42-58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3-5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8-12; 60.9%, 48.8% and 24.6% between weeks 20-24; and 59.7%, 48.3% and 24.6% between weeks 44-48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469-0.817) and patient's age (OR: 1.016; 95%CI: 1.005-1.026) were associated with 50% response at weeks 20-24. The variables that were associated with a higher reduction of headache days between weeks 20-24 were patient's age (0.068; 95% CI: 0.018-0.119) and headache days per month at baseline (0.451; 95% CI: 0.319-0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626-0.538) and daily headache at baseline (-2.718; 95% CI: -4.58-0.869) were associated with fewer reduction in the number of headache days between weeks 20-24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

[Arterial pathology in migraine: endothelial dysfunction and structural changes in the brain and systemic vasculature]. / Patologia arterial en la migraña: disfuncion endotelial y cambios estructurales en la vasculatura cerebral y sistemica.

INTRODUCTION: The pathophysiology underlying the association between migraine and other non-atherosclerotic vascular diseases is largely unknown. Endothelial dysfunction has been proposed as a common link. Besides, endothelial dysfunction is considered as a predictor of structural changes in the arterial walls. AIM: To review the current knowledge about the functional (endothelial dysfunction) and structural (arterial stiffness and atherosclerotic diseases) arterial properties associated with migraine. DEVELOPMENT: Studies of biological markers of endothelial dysfunction in peripheral blood, systemic and cerebral vasoreactivity, arterial stiffness indexes and direct visualization of macroscopic changes in the arterial wall have shown differences between patients with and without migraine, as well as between the different migraine subtypes. CONCLUSIONS: Endothelial dysfunction, as a predictor of structural changes in arteries, has been proposed as an early marker for vascular pathology associated with migraine. In migraine patients there is an increase of biomarkers of endothelial dysfunction, but the correlation with vasoreactivity studies does not allow definite conclusions. Available data do not allow to conclude that migraine is associated with macroscopic alterations outside the cerebral arterial bed.

TITLE: Patologia arterial en la migraña: disfuncion endotelial y cambios estructurales en la vasculatura cerebral y sistemica.Introduccion. La fisiopatologia subyacente a la asociacion entre migraña y otras enfermedades vasculares sistemicas no aterotromboticas no se conoce con certeza. La disfuncion endotelial se ha propuesto como nexo comun. A su vez, la disfuncion endotelial se considera como precursora de cambios estructurales en las paredes arteriales. Objetivo. Revisar el conocimiento actual acerca de las alteraciones funcionales (disfuncion endotelial) y estructurales (rigidez arterial y cambios ateroescleroticos) del lecho arterial asociadas a la migraña. Desarrollo. Estudios de marcadores biologicos de disfuncion endotelial en sangre periferica, vasorreactividad sistemica y cerebral, calculo de indices de rigidez arterial y visualizacion directa de cambios macroscopicos en la pared arterial han mostrado diferencias entre pacientes con y sin migraña, asi como entre los distintos subtipos de migraña. Conclusiones. La disfuncion endotelial, como precursora de cambios estructurales a nivel arterial, se postula como sustrato de la patologia vascular asociada a la migraña. La alteracion de marcadores biologicos es sugestiva de disfuncion endotelial en los pacientes con migraña; sin embargo, la correlacion con estudios de vasorreactividad no permite establecer conclusiones definitivas. Los datos disponibles no permiten concluir que la migraña se asocie con alteraciones macroscopicas fuera del lecho arterial cerebral.

[Is there overuse of neuroimaging procedures in patients with chronic migraine? An study in a Health Area in Asturias, Spain]. / ¿Se abusa de las técnicas de neuroimagen en pacientes con migraña crónica? Estudio en un área de salud del Principado de Asturias.

INTRODUCTION: There is a general perception of neuroimaging procedures overuse, mainly of CT scan, in patients with headache in Spain. AIM: To analyze the use of neuroimaging techniques, mainly CT scan as it is of free access in our region, in routine clinical practice in patients with chronic migraine (CM). PATIENTS AND METHODS: We reviewed the medical records of a consecutive series of women diagnosed as CM in our headache clinic. The data on consumption of neuroimaging procedures were collected at all levels (emergency department, inpatient ward and neurologic outpatient consultation). RESULTS: We included 139 women with CM. A total of 106 patients (76%) had at least one CT brain scan. Twenty-eight patients (20%) had 2 or more CT scans. In 6 of these patients (21%) there was a clinical reason for repeating the studies, while there was no reason in the remaining 22 (79%). MRI had been carried out in our headache clinic in 59 patients (42%). In 43 (73%) MRI was normal, in 9 (15%) the MRI showed nonspecific lesions in the white matter and in 7 patients (11%) MRI studies were abnormal. There was no direct relationship between MRI lesion and CM. There were 15 patients with CM (11%) without any neuroimaging study. CONCLUSIONS: We could not find a real overuse of neuroimaging techniques in patients with CM in our health area.

TITLE: Se abusa de las tecnicas de neuroimagen en pacientes con migraña cronica? Estudio en un area de salud del Principado de Asturias.Introduccion. Existe la creencia del abuso de las tecnicas de neuroimagen en pacientes con cefalea en nuestro medio. Objetivo. Analizar el consumo de tecnicas de neuroimagen, y fundamentalmente de la tomografia computarizada (TC), ya que es de acceso libre en nuestra area, en la practica clinica habitual en pacientes con migraña cronica (MC). Pacientes y metodos. Se revisan las historias clinicas de una serie de mujeres consecutivas diagnosticadas en nuestra consulta de cefaleas de MC. Se recogieron datos acerca de la realizacion de tecnicas de neuroimagen a todos niveles (urgencias, consultas y pacientes ingresados). Resultados. Se incluyeron 139 mujeres con MC. Un total de 106 pacientes (76%) tenia al menos una TC de craneo y 28 (20%) dos o mas estudios de TC de craneo. En seis de estas pacientes (21%) existia justificacion clinica para la repeticion del estudio, pero no en las 22 (79%) restantes. Ya en nuestro servicio se solicito resonancia magnetica (RM) a 59 pacientes (42%). En 43 (73%), la RM fue normal; en nueve (15%) puso de manifiesto lesiones inespecificas en la sustancia blanca; y en siete (11%) fue patologica, si bien en ninguno de estos casos habia relacion directa entre la lesion de la RM y la clinica de MC. En 15 pacientes con MC (11%) no se habia solicitado ningun estudio de neuroimagen. Conclusiones. En contra de nuestra hipotesis inicial, no encontramos un abuso de las tecnicas de neuroimagen en pacientes con MC en nuestra area de salud.

[Rizatriptan: experience after 15 years of clinical use]. / Rizatriptan: experiencia tras 15 años de uso clinico.

We review the development of rizatriptan, one of the seven 5-HT1B/1D agonists available for the symptomatic treatment of migraine, emphasizing the most relevant contributions carried out from our country. Rizatriptan has shown the quickest onset of action, both in controlled studies and in the different metaanalyses, which translates in high efficacy levels at two hours. Its tolerability and safety profile is similar to that of the other compounds in this pharmacological group. Postlaunching studies have shown that its high efficacy leads to pharmacoeconomic savings and to a robust preference and satisfaction by the patient for this triptan. Its efficacy is improved with an early use within migraine attacks and recent data have shown also efficacy in adolescents. This global profile places rizatriptan as a triptan of first choice for any kind of migraine attacks.

TITLE: Rizatriptan: experiencia tras 15 años de uso clinico.En este trabajo se pasa revista al desarrollo del rizatriptan, uno de los siete agonistas 5-HT1B/1D disponibles para el tratamiento sintomatico de la migraña, prestando especial atencion a las aportaciones mas relevantes llevadas a cabo desde España. El rizatriptan ha demostrado ser el triptan con inicio de accion mas rapido, tanto en estudios comparativos controlados como en diversos metaanalisis, lo que se ha traducido en elevados niveles de eficacia a las dos horas. El perfil de seguridad y tolerabilidad de este triptan es similar al del resto de los compuestos de este grupo farmacologico. Los estudios poscomercializacion han evidenciado que su eficacia se traduce en ahorro farmacoeconomico y preferencia y satisfaccion del paciente con este triptan. Su eficacia mejora con su uso precoz dentro de la crisis de migraña, y datos recientes indican que el rizatriptan es util tambien en preadolescentes. Este perfil global posiciona al rizatriptan como un triptan de eleccion para cualquier tipo de crisis de migraña.