Migréna je časté neurologické onemocnění, které postihuje značnou část celosvětové populace. Nedávným pokrokem v léčbě tohoto onemocnění v České republice se stalo schválení úhrady pro rimegepant v akutní léčbě migrény. Rimegepant, lék ze skupiny gepantů, působí jako antagonista CGRP receptoru. Vzhledem k rozdílnému mechanismu účinku může být účinným řešením pro pacienty, kteří nereagují na tradiční léčbu triptany nebo kteří triptany netolerují. Je prvním lékem, který má duální využití. Lze ho použít k terapii migrenózní ataky, zároveň je vhodný i pro preventivní léčbu, v této indikaci však úhradu stanovenu nemá. Rimegepant má příznivý bezpečnostní profil, během jeho užívání nebyla pozorována hepatotoxicita ani kardiotoxicita, nemá ani vazokonstrikční potenciál. Míra výskytu nežádoucích účinků je nízká a ve většině případů se jednalo o mírné nebo středně závažné nežádoucí účinky. Možnost širšího použití rimegepantu v klinické praxi díky jeho schválené úhradě posouvá standardy moderní péče o pacienty s migrénou.
Migraine is a common neurological disorder that affects a significant portion of the global population. The possibilities of its treatment in the Czech Republic have recently been enriched by the approval of reimbursement for rimegepant in the context of acute migraine treatment. Rimegepant, a drug from the gepant group, acts as a CGRP receptor antagonist. Due to its different mechanism of action, it can be an effective solution for patients who do not respond to traditional triptan treatments or who cannot tolerate triptans. It is the first medication with dual use, suitable for treating migraine attacks and also for preventive treatment; however, reimbursement has not yet been established for the latter indication. Rimegepant has a favorable safety profile, with no observed hepatotoxicity or cardiotoxicity, and it does not have vasoconstrictive potential. The frequency of side effects is low, most of them being mild to moderate. The broader use of rimegepant in clinical practice, enabled by its approved reimbursement, advances the standards of modern care for patients with migraine.
Cíl: V uvedené studii retrospektivně hodnotíme pacienty našeho centra na biologické léčbě migrény protilátkami CGRP nasazené po schválení plné úhrady od března do konce roku 2020. Do sledování byli zařazeni pouze pacienti s aplikací erenumabu a fremanezumabu, neboť galkanezumab byl schválen až v říjnu 2020. Soubor a metodika: Soubor tvoří 130 pacientů, z toho 118 žen (90,8 %) a 12 mužů (9,2 %) v průměrném věku 46,2 (21–76) let. Primárním cílem bylo vyhodnotit efekt terapie po 3, 6, 9 a 12 měsících, dále počet non-respondérů (redukce migrenózních dnů v měsíci [monthly migraine day; MMD] méně než 50 %), redukci dní s nadužíváním akutní medikace (medication overuse; MOH) a vztah k trvání onemocnění, počtu předchozích profylaxí, migréně v rodinné anamnéze (RA) a komorbiditám. Sledován byl výskyt nežádoucích účinků (NÚ). Výsledky: Průměrný počet MMD před nasazením léčby byl 12,2. Po 3 měsících došlo ke snížení MMD o 60,5 % (na 4,7), v dalších měsících účinnost ještě dále stoupala na více než 70 %, větší účinnosti bylo dosaženo u chronické migrény (CM) oproti epizodické (EM). Po 12 měsících činil pokles u EM 69,9 %, a u CM 75,9 %. Naopak účinnost léčby u pacientů s pozitivní RA a bez ní byla prakticky totožná. Po 12 měsících léčby byl efekt výraznější u pacientů s konkomitantní MOH (pokles o 76,2 %) než bez MOH. Účinnost u mužů a u žen byla obdobná. 52 pacientů před nasazením biologické léčby užívalo dvě profylaktika, 45 pacientů tři a 29 pacientů čtyři a více profylaktik. Účinnost biologické léčby byla ve všech třech skupinách podobná (po 12 měsících pokles MMD o 70,3 vs. 73,2 vs. 70,7 %). Účinnost erenumabu a fremanezumabu (podávání v jedno- či tříměsíčních intervalech) se významně nelišila. Kvůli nedostatečnému efektu byla léčba vysazena jen u šesti pacientů. NÚ se vyskytly pouze u 10 (7,7 %) pacientů, z toho u devíti (8,6 %) pacientů léčených erenumabem a u jednoho (4,8 %) pacienta léčeného fremanezumabem. Pro NÚ byla terapie vysazena pouze u jednoho pacienta na erenumabu (obstipace). Závěr: Protilátky CGRP (calcitonin gene-related peptide) v léčbě migrény jsou v našem souboru pacientů významně účinné a dobře tolerované, stejně jako v předchozích randomizovaných a observačních studiích.
Aim: In this study, we retrospectively evaluate our center patients on the biological treatment of migraine with CGRP antibodies used after full reimbursement approval from March to the end of 2020. Only patients receiving erenumab and fremanezumab were enrolled, as galcanezumab was not approved until October 2020. Patients and methods: The sample consists of 130 patients, including 118 women (90.8%) and 12 men (9.2%) with an average age of 46.2 (21–76) years. The primary objective was to evaluate the effect of therapy at 3, 6, 9, and 12 months, the number of non-responders (monthly migraine day [MMD] reduction lower than 50%), reduction of acute medication overuse (MOH) days, relationship to disease duration, number of previous prophylaxes, migraine in family history (FH) and comorbidities. The incidence of adverse events (AE) was monitored. Results: The average number of MMD before treatment was 12.2. After 3 months, the MMD decreased by 60.5% (to 4.7), and in the following months, the effectiveness increased even further to more than 70%; greater effectiveness was achieved in chronic migraine (CM) compared to episodic (EM). After 12 months, the decrease was 69.9% for EM and 75.9% for CM. In contrast, the eff ectiveness of treatment in patients with and without positive FH was practically the same. After 12 months of treatment, the effect was more pronounced in patients with MOH (76.2% decrease) than without MOH. Efficacy was similar in men and women. Fifty-two patients received two prophylactics before starting biological therapy, 45 patients had three prophylactic drugs and 29 patients used four prophylactic drugs. The effectiveness of biological therapy was similar in all three groups (after 12 months, the decrease in MMD was 70.3 vs. 73.2 vs. 70.7%). The efficacy of erenumab and fremanezumab (administered in month or three-month intervals) was not significantly different. Therapy was discontinued due to insufficient effect only in 6 patients. AE occurred in only 10 (7.7%) patients, of whom 9 (8.6%) were treated with erenumab and 1 (4.8%) was treated with fremanezumab. Therapy was discontinued due to AE (constipation) only in 1 patient on erenumab. Conclusion: CGRP (calcitonin generelated peptide) antibodies in the treatment of migraine are significantly effective and well tolerated in our group of patients in accordance with previous randomized and observational trials.
BACKGROUND: Monoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab. METHODS: ESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women. RESULTS: Out of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs. CONCLUSIONS: The present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.
- MeSH
- antagonisté CGRP receptorů farmakologie terapeutické užití MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- peptid spojený s genem pro kalcitonin MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Introduction: Assessing the impact of migraine preventive treatments on acute medication consumption is important in clinical evaluation. The number of acute medication intakes per each monthly migraine day (MMD) could provide insights on migraine burden and represent a new proxy of treatment effectiveness in clinical trials and real-life studies. We evaluated the effect of monoclonal antibodies acting on calcitonin gene-related peptide (CGRP) pathway on the consumption of migraine acute medication in real-life. Methods: In two headache centers in Prague (CZ), we included and followed up to 6 months consecutive patients treated with MoAbs acting on CGRP (erenumab or fremanezumab). For each month of treatment, we reported monthly drug intake (MDI) in doses of any medication, migraine-specific (MS), and non-migraine-specific (non-MS) medications, and computed a ratio between MMDs and MDI, i.e., Migraine Medication Index (MMI) for MS and non-MS medications. Results: We included 90 patients (91.1% women) with a median age of 47 [interquartile range (IQR) 42-51] years; 81 (90.0%) treated with erenumab and 9 (10.0%) with fremanezumab. Median MMDs decreased from 11 (IQR 8-14) at baseline to 4 (IQR 2-5) at Month 3 (p < 0.001 vs. baseline) and 3 (IQR 2-6) at Month 6 (p < 0.001 vs. baseline). Median MDI decreased from 15 drug intakes (IQR 11-20) at baseline to four drug intakes (IQR 2-7) at Month 3 (p < 0.001) and four drug intakes (IQR 2-7) at Month 6 (p < 0.001).The corresponding MDIs for MS medications were 10 (IQR 6-14) at baseline, 3 (IQR 1-5, p < 0.001) at Month 3, and 2 (IQR 0-4, p < 0.001) at Month 6. Monthly drug intakes for non-MS medications were 4 (IQR 0-9) at baseline, 1 (IQR 0-3, p < 0.001) at Month 3 and at Month 6.Median MMI decreased from 1.32 (IQR 1.11-1.68) at baseline to 1.00 (IQR 1.00-1.50, p < 0.001) at Month 3 and 1.00 (IQR 1.00-1.34, p < 0.001) at Month 6. Conclusions: We confirmed that MoAbs acting on CGRP pathway decrease acute migraine medication consumption. We proposed a new index that can be easily applied in clinical practice to quantify migraine burden and its response to acute medication. Our index could help optimizing migraine acute treatment in clinical practice.
- Publikační typ
- časopisecké články MeSH
Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor. Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9-12 of treatment compared with baseline: 0-29%, 30-49%, 50-75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9-12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes. Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9-12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50-74% response, 35 (13.7%) had a 30-49% response, and 86 (33.6%) had a 0-29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes. Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.
- Publikační typ
- časopisecké články MeSH
