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Inicio Neurología (English Edition) Failure of monoclonal antibodies against CGRP or its receptor does not imply lac...
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Vol. 36. Issue 8.
Pages 638-640 (October 2021)
Vol. 36. Issue 8.
Pages 638-640 (October 2021)
Letter to the Editor
Open Access
Failure of monoclonal antibodies against CGRP or its receptor does not imply lack of efficacy of other drugs from the same class
El fracaso a anticuerpos monoclonales frente a CGRP o su receptor no implica la inefectividad a otros fármacos de la misma clase terapéutica
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J. Porta-Etessama,b,c,
Corresponding author
jporta@yahoo.com

Corresponding author.
, N. González-Garcíaa, Á.L. Guerrerod,e,f, D. García-Azorínd,f
a Unidad de Cefaleas, Servicio de Neurología, Hospital Clínico Universitario San Carlos, Madrid, Spain
b Departamento de Medicina, Universidad Complutense de Madrid, Madrid, Spain
c Instituto de Investigación Biomédica, Hospital Clínico San Carlos, Madrid, Spain
d Unidad de Cefaleas, Servicio de Neurología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
e Departamento de Medicina, Universidad de Valladolid, Valladolid, Spain
f Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
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Table 1. Demographic and clinical variables of our series.
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Dear Editor:

In August 2018, the European Medicines Agency1 approved the first preventive medications for migraine, acting on the calcitonin gene-related peptide (CGRP) pathway. These drugs have been shown to reduce the number of headache and migraine days per month in randomised placebo-controlled clinical trials including patients with episodic and chronic migraine presenting failure of and/or poor tolerance to up to 2/4 previous preventive treatments.2–8 In the light of the above, these drugs were approved in Europe and in Spain, with the associated costs being covered by the Spanish National Health System for patients with high-frequency episodic migraine presenting failure of 3 preventive medications and patients with chronic migraine presenting failure of 3 preventive medications including botulinum toxin.9 Despite the availability of the Spanish national guidelines, the approval of these drugs has varied between autonomous communities, and even between hospital pharmacy departments, with justification for approving one drug or another being based on bioequivalence or efficiency criteria.

From a theoretical viewpoint, we may expect to find differences in terms of effectiveness and adverse reactions, although these will probably be small.10,11 The therapeutic target is not exactly the same: erenumab targets the CGRP receptor, whereas galcanezumab, fremanezumab, and eptinezumab target circulating CGRP.11–13 Erenumab is a human monoclonal antibody, whereas the other drugs are humanised monoclonal antibodies.12,13 Isolated cases have been reported of patients who respond to a drug after failure of another drug from the same class.14 Given that decisions made by pharmacy committees are based on the available evidence, we deem it highly relevant to report a series of patients presenting adequate response to one drug following failure of other drugs from the same class.

Our series includes 7 patients with chronic migraine and prior treatment with 3-14 preventive drugs (mean, 9.5) and presenting different responses to 2 different monoclonal antibodies after 3 months of treatment. Table 1 summarises the drugs administered, the reason for drug switching, and treatment outcomes.

Table 1.

Demographic and clinical variables of our series.

Patient 
Sex 
Age  54  62  34  44  24  50  33 
Migraine type  CM  CM  CM  CM  CM  CM  CM 
Migraine progression time before first MAb  21 years  40 years  14 years  30 years  12 years  4 years  14 years 
Preventive treatments before first MAb  BB, TPM, ZNS, PGB, AML, DLX, MLT, RBF, BTX, LSN, CDS, AnBlock (n = 12)  BB, TPM, ZNS, PGB, AML, DLX, MLT, RBF, BTX, LSN, CDS, MTZ, CoQ10, AnBlock (n = 14)  BB, TPM, ZNS, PGB, AML, DLX, MLT, RBF, BTX, LSN, CDS, AnBlock (n = 12)  BB, TPM, ZNS, PGB, AML, DLX, MLT, BTX, LSN (n = 9)  BB, TPM, ZNS, PGB, AML, DLX, MLT, BTX, LSN (n = 9)  FLN, BB, TPM, ZNS, BTX, AMT, DSV, AnBlock (n = 8)  TPM, AMT, BB, AnBlock (n = 3) 
First MAb  Eren  Eren  Galc  Eren  Galc  Frem  Frem 
HDM before first MAb  30  30  30  30  30  25  19 
MDM before first MAb  12  14  10  12  14  10 
HDM after first MAb  24  30  30  30  16 
MDM after first MAb  13  12 
Reason for switching medication  AE  AE  Effect.  Effect.  Effect.  Pharm.  Pharm. 
Second MAb  Galc  Galc  Eren  Galc  Eren  Galc  Galc 
HDM after second MAb  11  10  30  22  30  20 
MDM after second MAb   

AE: adverse events; AML: amitriptyline; AnBlock: anaesthetic block; BB: beta blockers; BTX: botulinum toxin; CDS: candesartan; CM: chronic migraine; CoQ10: coenzyme Q10; DLX: duloxetine; DSV: desvenlafaxine; Effect.: insufficient effectiveness; Eren: erenumab; Frem: fremanezumab; Galc: galcanezumab; HDM: headache days per month; LSN: lisinopril; M: man; MAb: monoclonal antibody; MDM: migraine days per month; MLT: melatonin; MTZ: mirtazapine; PGB: pregabalin; Pharm.: treatment approval by hospital pharmacy department; RBF: riboflavin; TPM: topiramate; W: woman; ZNS: zonisamide.

Migraine is the third most prevalent disease in the world and the leading cause of years lived with disability between the ages of 15 and 49 years, a period when personal, academic, and professional productivity is at its peak.15 Unlike in other neurological diseases, the disability caused by frequent, disabling migraine attacks can be prevented with pharmacological treatments, which have been shown to reduce headache frequency and intensity, work and school absences and presenteeism, and the use of symptomatic treatments.16 Despite the small size of our series, we feel that reporting these cases contributes new evidence to support the use of a second drug acting on the CGRP pathway in patients presenting poor response to another drug from the same family; we encourage other authors to conduct further research on the topic.

Conflicts of interest

The authors have no conflicts of interest to declare.

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Please cite this article as: Porta-Etessam J, González-García N, Guerrero ÁL, García-Azorín D. El fracaso a anticuerpos monoclonales frente a CGRP o su receptor no implica la inefectividad a otros fármacos de la misma clase terapéutica. Neurología. 2021;36:638–640.

Copyright © 2020. Sociedad Española de Neurología
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