RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

[Zonisamide in the preventive treatment of refractory migraine]. / Zonisamida en el tratamiento preventivo de la migraña refractaria.

INTRODUCTION: Chronic migraine refractory to preventive treatment is a common clinical situation in general neurology clinics. The aim is to analyse our experience with zonisamide in the preventive treatment of patients with frequent refractory migraine. PATIENTS AND METHODS: Those patients with no response or intolerance to topiramate and at least one more preventative received zonisamide. This drug was increased 25 mg per week up to 200 mg/day. The efficacy of zonisamide was evaluated in terms of 'response' (reduction in attack frequency below 50%) at the third month of treatment. RESULTS: Our series comprises a total of 172 patients, with ages ranging from 22 to 69 years. 85% were women. The final dosage of zonisamide was 50-200 mg/day, with the 100 mg/day being the most frequently administered dose. Zonisamide was efficacious (response) in 76 (44%) patients; response being excellent in 22 (13%). MIDAS score was reduced by 43.2%. Zonisamide was not tolerated by 27% of the patients, mainly due to subjective mental slowness or digestive symptoms. CONCLUSIONS: These results, obtained in a big sample of patients refractory or intolerant to topiramate and other preventatives, indicate that, at least in conditions of daily clinical practice, zonisamide, at relatively low dosages, is an option to be considered for the preventive treatment of patients with frequent migraine.

Zonisamida en el tratamiento preventivo de la migraña refractaria / Zonisamide in the preventive treatment of refractory migraine

Introducción. La migraña crónica refractaria al tratamiento preventivo habitual es una situación frecuente en consultas de neurología. Se pretende analizar la experiencia con zonisamida en el tratamiento de pacientes con migraña frecuente refractaria. Pacientes y métodos. Aquellos pacientes sin respuesta o con intolerancia a topiramato y al menos otro fármaco preventivo para la migraña recibieron zonisamida. El fármaco se incrementó a razón de 25 mg/semana, hasta un máximo de 200 mg/día. La eficacia de la zonisamida se evaluó en términos de ‘respuesta’ (disminución en la frecuencia de las crisis al menos del 50%) al tercer mes del tratamiento. Resultados. Nuestra serie comprende 172 pacientes de entre 22 y 69 años. El 81% eran mujeres. Las dosis de zonisamida oscilaron entre 50 y 200 mg/día, y la dosis más frecuentemente administrada fue de 100 mg/día. La zonisamida mostró eficacia (respuesta) en 76 (44%) de los pacientes; la respuesta fue excelente en 22 (13%). La puntuación en el test de MIDAS se redujo en un 43,2%. Un 27% de los pacientes no toleró el fármaco, fundamentalmente por bradipsiquia subjetiva o clínica digestiva. Conclusiones. Estos resultados, obtenidos en un número amplio de pacientes refractarios o intolerantes a topiramato y otros fármacos, indican que, al menos en condiciones de práctica clínica, la zonisamida, en dosis relativamente bajas, es una opción que se debe considerar en el tratamiento preventivo del paciente con migraña frecuente

Introduction. Chronic migraine refractory to preventive treatment is a common clinical situation in general neurology clinics. The aim is to analyse our experience with zonisamide in the preventive treatment of patients with frequent refractory migraine. Patients and methods. Those patients with no response or intolerance to topiramate and at least one more preventative received zonisamide. This drug was increased 25 mg per week up to 200 mg/day. The efficacy of zonisamide was evaluated in terms of ‘response’ (reduction in attack frequency below 50%) at the third month of treatment. Results. Our series comprises a total of 172 patients, with ages ranging from 22 to 69 years. 85% were women. The final dosage of zonisamide was 50-200 mg/day, with the 100 mg/day being the most frequently administered dose. Zonisamide was efficacious (response) in 76 (44%) patients; response being excellent in 22 (13%). MIDAS score was reduced by 43.2%. Zonisamide was not tolerated by 27% of the patients, mainly due to subjective mental slowness or digestive symptoms. Conclusions. These results, obtained in a big sample of patients refractory or intolerant to topiramate and other preventatives, indicate that, at least in conditions of daily clinical practice, zonisamide, at relatively low dosages, is an option to be considered for the preventive treatment of patients with frequent migrainev