Medicamentos biocomparables en México: la postura del Colegio Mexicano de Reumatología, 2012 / Biosimilar drugs in Mexico: Position of the Mexican College of Rheumatology, 2012

Los medicamentos biotecnológicos (MBT) son moléculas complejas cuyo proceso de elaboración impide replicar con gran exactitud la sustancia original, por lo que no existe una equivalencia absoluta entre el fármaco original (innovador) y el biocomparable. Los MBT han probado su eficacia en diversas afecciones reumáticas, aunque su alto coste impide su utilización en muchos pacientes. Diversas patentes de medicamentos biotecnológicos han expirado o expirarán próximamente, detonando así el desarrollo de fármacos estructuralmente similares y probablemente con eficacia y seguridad comparable a los medicamentos innovadores, aunque estas características deben ser probadas. La Ley General de Salud Mexicana actual contempla el registro de estos medicamentos para su utilización en nuestro país. Este documento es una reflexión de miembros del Colegio Mexicano de Reumatología, farmacólogos e investigadores en epidemiología, en conjunción con nuestras autoridades sanitarias, sobre los estudios científicos necesarios de los biocomparables previos y posterior a su incursión en el mercado mexicano (AU)

Biotechnological drugs (BTDs) are complex molecules whose manufacturing process precludes the ability to identically reproduce the structure of the original product, and therefore there cannot be an absolute equivalence between the original (innovative) medication and its biosimilar counterpart. BTDs have been proven useful in the treatment of several rheumatic diseases, however their high cost has prevented their use in many patients. Several BTD patents have expired or are close to expire, triggering the development of structurally similar drugs with efficacy and safety profiles comparable to the innovative compound; however, these must be evaluated through evidence based medicine. The Mexican General Health Law contemplates the registry of these biosimilar drugs for their use in our country. This document is a forethought from members of the Mexican College of Rheumatology, pharmacologists, and epidemiologists, in accordance with Mexican health authorities regarding the necessary scientific evidence required to evaluate the efficacy and safety of biosimilar drugs before and after their arrival to the Mexican market (AU)

Biosimilar drugs in Mexico: position of the Mexican College of Rheumatology, 2012.

Biotechnological drugs (BTDs) are complex molecules whose manufacturing process precludes the ability to identically reproduce the structure of the original product, and therefore there cannot be an absolute equivalence between the original (innovative) medication and its biosimilar counterpart. BTDs have been proven useful in the treatment of several rheumatic diseases, however their high cost has prevented their use in many patients. Several BTD patents have expired or are close to expire, triggering the development of structurally similar drugs with efficacy and safety profiles comparable to the innovative compound; however, these must be evaluated through evidence based medicine. The Mexican General Health Law contemplates the registry of these biosimilar drugs for their use in our country. This document is a forethought from members of the Mexican College of Rheumatology, pharmacologists, and epidemiologists, in accordance with Mexican health authorities regarding the necessary scientific evidence required to evaluate the efficacy and safety of biosimilar drugs before and after their arrival to the Mexican market.

Validity of the COPCORD core questionnaire as a classification tool for rheumatic diseases.

OBJECTIVE: Rheumatic diseases are vastly underdiagnosed and undertreated, particularly among minorities and those of low socioeconomic status. The WHO-ILAR Community Oriented Program in the Rheumatic Diseases (COPCORD) advocates screening of musculoskeletal complaints in the community. The objective of this study was to evaluate the performance of the COPCORD Core Questionnaire (CCQ) as a diagnostic tool for rheumatic diseases. METHODS: We conducted a cross-sectional study designed in parallel with a large COPCORD survey in Mexico. A subsample of 17,566 questionnaires, selected from 4 of the 5 states included in a national COPCORD survey were included in the analysis as a diagnostic test to evaluate sensitivity, specificity, receiver operating characteristics curve (ROC), and positive likelihood ratio (LR+) of the CCQ as a case-detection tool for rheumatic diagnosis and for the most frequent diagnoses identified in the survey, osteoarthritis, regional rheumatic pain syndromes, and rheumatoid arthritis (RA). Logistic regression with the questions with LR+ ≥ 1 was performed to identify the strength of association (OR) for each question. RESULTS: Pain in the last 7 days, high pain score (> 4), and previous diagnosis were the questions with highest LR+ for diagnosis, and for diagnosis of RA treatment with NSAID. The variables that contributed most to the model were pain in the last 7 days (OR 2.0, 95% CI 1.8-2.3), NSAID treatment (OR 3.3, 95% CI 3.0-3.7), a high pain score (OR 1.15, 95% CI 1.13-1.17), and having a previous diagnosis (OR 1.4, 95% CI 1.3-1.6). These 4 questions had R(2) = 0.24, p < 0.01, for detection of any rheumatic diagnosis. The single variable that explains 16% (OR 1.33, 95% CI 1.31-134) of variance was a high pain score in the last 7 days. CONCLUSION: Some variables were identified in the CCQ that could be combined in a brief version for case detection of rheumatic diseases in community surveys. The validity of this proposal has to be tested against the original version.

[Secondary Raynaud's syndrome: skin blood flow decrease between the ischemic episodes and prolongation of the vasoconstriction during the respiratory maneuvers]. / Síndrome de Raynaud secundario: disminución del flujo sanguíneo de la piel entre los episodios isquémicos y prolongación de la vasoconstricción con las maniobras respiratorias.

UNLABELLED: The Raynaud's syndrome is an episodic skin ischemia manifested by pallor, cyanosis and erythema of the fingers in response to cold or emotional stress. The exact pathophysiology is unknown but it has been hypothetised that may be due to an autonomic alteration in the sympathetic innervation of skin blood vessels. OBJECTIVE: To study the changes of heart rate and skin blood flow (SBF) in healthy subjects and in patients with secondary Raynaud's syndrome during different respiratory maneuvers: 1. spontaneous respiration; 2. rhythmic respirations (RR), 3. sudden inspirations (SI), and 4. Valsalva maneuver (VM). METHODS: We studied 22 healthy subjects and 22 patients with secondary Raynaud's syndrome. The variables measured were: 1) RR intervals; 2) amplitudes of SBF; 3) percentage of decrease of SBF; 4) latency of the maximum decrease of SBF. RESULTS: In all patients with secondary Raynaud's syndrome the SBF was decreased basally during spontaneous rations and during all respiratory maneuvers (p < 0.001). The mean latency of recovery of the SBF was prolonged during sudden deep inspiration. The patients with Raynaud also had significant basal tachycardia at rest (p < 0.003). CONCLUSIONS: The basal skin blood flow during spontaneous respirations and in asymptomatic periods is decreased in patients with Raynaud's syndrome; this may be related to endothelial arterioral damage. The SBF was also significantly decreased dynamically during sudden inspirations (SI), rhythmic breathing (RR) and Valsalva maneuver (VM). This dynamic change suggests sympathetic hyperactivity.

Síndrome de Raynaud secundario: disminución del flujo sanguíneo de la piel entre los episodios isquémicos y prolongación de la vasoconstricción con las maniobras respiratorias / Secondary Raynaud's syndrome: skin blood flow decrease between the ischemic episodes and prolongation of the vasoconstriction during the respiratory maneuvers

El síndrome de Raynaud se caracteriza por isquemia cutánea digital episódica, manifestada por palidez, cianosis y rubor de los dedos de manos y pies expuestos al frío o cuando el paciente está sujeto a un estrés emocional. No se conoce el mecanismo fisiopatológico exacto; la hipótesis más invocada es una alteración autonómica en la inervación simpática de los vasos sanguíneos de la piel. Objetivo: Estudiar los cambios de la frecuencia cardíaca y el flujo sanguíneo de la piel (FSP) en sujetos sanos y en pacientes con síndrome de Raynaud durante las siguientes condiciones: 1. respiración espontánea (RE), 2. respiración rítmica (RR), 3. inspiración profunda repentina (IPR), 4. maniobra de Valsalva (MV). Método: Se estudiaron 22 sujetos sanos y 22 pacientes con síndrome de Raynaud secundario. Las variables medidas fueron: 1. intervalo R-R; 2. amplitud de FSP; 3. porcentaje de disminución de FSP; 4. latencia de la máxima disminución del FSP. Resultados: Los pacientes con síndrome de Raynaud presentaron mayor taquicardia basal. La amplitud del FSP se encontró disminuido durante la respiración espontánea y durante las maniobras respiratorias (P < 0.001). La vasoconstricción estuvo prolongada ya que la latencia promedio de recuperación del FSP estuvo prolongada en IPR y MV en comparación de los sujetos controles. Conclusión: La amplitud del FSP basal está disminuida en los pacientes con síndrome de Raynaud, durante períodos asintomáticos; esto sugiere daño endotelial. También se encontró disminuido con las diversas maniobras respiratorias (RR, IPR y MV). Este cambio dinámico sugiere hiperactividad simpática hacia los vasos sanguíneos de la piel.

The Raynaud's syndrome is an episodic skin ischemia manifested by pallor, cyanosis and erythema of the fingers in response to cold or emotional stress. The exact pathophysiology is unknown but it has been hypothetised that may be due to an autonomic alteration in the sympathetic innervation of skin blood vessels. Objective: To study the changes of heart rate and skin bloodflow (SBF) in healthy subjects and in patients with secondary Raynaud's syndrome during different respiratory maneuvers: 1. spontaneous respiration; 2. rhythmic respirations (RR), 3. sudden inspirations (SI), and 4. Valsalva maneuver (VM). Methods: We studied 22 healthy subjects and 22 patients with secondary Raynaud's syndrome. The variables measured were: 1) RR intervals; 2) amplitudes of SBF; 3) percentage of decrease of SBF; 4) latency of the maximum decrease of SBF. Results: In all patients with secondary Raynaud's syndrome the SBF was decreased basally during spontaneous respirations and during all respiratory maneuvers (p < 0.001). The mean latency of recovery of the SBF was prolonged during sudden deep inspiration. The patients with Raynaud also had significant basal tachycardia at rest (p < 0.003). Conclusions: The basal skin blood flow during spontaneous respirations and in asymptomatic periods is decreased in patients with Raynaud's syndrome; this may be related to endothelial arterioral damage. The SBF was also significantly decreased dynamically during sudde3n inspirations (SI), rhythmic breathing (RR) and Valsalva maneuver (VM). This dynamic change suggests sympathetic hyperactivity.