Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(−receptor) antibodies

Abstract

Background Migraine preventive treatment with CGRP(−receptor) monoclonal antibodies (mAbs) has a positive effect on patients’ health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(−receptor) mAbs after 6–12 months. We aimed to evaluate headache-specific and generic HRQoL for three months after discontinuation of CGRP(−receptor) mAb treatment. Methods We conducted a prospective, longitudinal cohort study, including patients with migraine after 8–12 months of therapy with a CGRP(−R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-specific HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12). Questionnaires’ total scores were compared across the three observation points using nonparametric procedures. Results The study cohort consisted of n = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab and n = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was 59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients’ lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by − 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened significantly during treatment discontinuation: The PCS-12 total score decreased by − 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by − 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires’ scores but the MCS-12 were already significant in the first month of the drug holiday (V2). Conclusions Our results show a significant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(−R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(−R) mAbs.

Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

“…CGRP/(R)-AKs: Erenumab, Galcanezumab, Fremanezumab Eptinezumab Zusammenfassend zeigen die bisherigen Daten (10 Studien, 2171 Patienten), dass nach Absetzen einer erfolgreichen Migräneprophylaxe mit CGRP/(R)-AK bei der Mehrzahl der Patienten wieder eine schrittweise Zunahme der Migränefrequenz, der migränebedingten Alltagseinschränkungen und eine Zunahme des Bedarfs an Akutmedikation eintritt [30][31][32][33][34][35][36][37][38][39]. Die Studien variieren in der Methodik (retrospektiv versus prospektiv, kontrolliert versus "realworld"-Daten, Fallzahlen, Therapie-und Nachbeobachtungszeiträume, chronische versus episodische Migräne, mit versus ohne Medikamentenübergebrauch, untersuchte Wirkstoffe), was die Aussagekraft direkter Vergleiche einschränkt.…”

“…In 3 der 10 Publikationen wurde berichtet, dass auch nach 3 Monaten Therapiepause die mittleren MMDs zwar signifikant zum letzten Therapiemonat anstiegen, jedoch weiterhin geringer waren als zur Baseline [30,31,40]. Hier sind Studiendaten zur gesundheitsbezogenen Lebensqualität während der Therapiepause mit CGRP/(R)-AK zu beachten, die bereits in Woche 8-16 nach Therapieende eine signifikante Zunahme der kopfschmerzbedingten Einschränkung der Alltagsaktivitäten und der Lebensqualität zeigen [37]. Ist eine Fortsetzung der Therapie mit CGRP/(R)-AK nötig, so belegen die dazu bislang publizierten Studien, dass die Mehrzahl der Patienten nach Wiederbeginn der CGRP/(R)-AK-Therapie genauso gut wie in der initialen Behandlung ansprechen [30,32,35].…”

Migraine: from pathophysiology to treatment

“…These treatments have persistently confirmed their efficacy in phase 3 trials [162][163][164][165][166][167][168][169][170][171][172][173][174], with convenient dosing, faster onset of efficacy and mild to moderate adverse events [175,176]. Further, real-world studies have shown improvement with mABs and worsening of migraine frequency following discontinuation, with most patients resuming treatment as soon as possible following breaks due to regulatory restrictions [177][178][179][180]. The European Headache Federation currently recommends CGRP mABs as a first-line option for migraine prevention, with treatment to be continued as long as needed [181], although in most jurisdictions, this is not possible to operationalize easily.…”

Anticuerpos monoclonales anti-PRGC y modificación de la historia natural de la migraña

“…En segundo lugar, se han practicado varios estudios de vida real, en relación con las suspensiones obligatorias en algunos países europeos de los tratamientos con anticuerpos anti-PRGC tras 6-12 meses (Tabla 2). El empeoramiento de la migraña objetivado en estos estudios tras la retirada parece ser más severo de lo comunicado en los pacientes de los ensayos clínicos 38,39,40,41,44 . Se han reportado empeoramientos rápidos ya desde el primer mes tras la retirada 40 .…”

“…En algunos se objetiva una frecuencia de DMM equiparable a los registros basales de los pacientes a los tres meses sin tratamiento 39,45 y en otros a los cuatro meses 41 . Tras la retirada del tratamiento aumenta el consumo de medicación aguda y la insatisfacción del pacien-te 39 , empeoran las escalas de calidad de vida e impacto de la cefalea 38 , y una proporción creciente de pacientes vuelve a cumplir criterios de migraña crónica y de uso excesivo de medicación sintomática 39 . En un estudio de Raffaelli et al, además, se objetivó un empeoramiento más rápido de los pacientes con erenumab (ya el segundo mes tras la retirada) respecto a galcanezumab y fremanezumab (a partir del tercer mes), quizás por la vida media más corta del primero 41 .…”