Long-term therapy with itolizumab is safe and effective for patients with moderate to severe psoriasis: Results from an expanded-access program.

Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin.

Background: Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor. It was approved in Cuba for the indication of inoperable malignant tumors of the esophagus of epithelial origin. The purpose of this study was to evaluate the safety, overall and progression-free survival, clinical response, and quality of life, in adult patients with inoperable esophageal tumors of epithelial origin treated with nimotuzumab in a practical context. Material and Methods. The number of patients who developed adverse events was determined, and the frequency, seriousness, causality, and severity of these adverse events were determined. It also determined the median of survival and progression-free survival and rates at 12 and 24 months and the quality of life. Results: A total of 111 patients were included. The proportion of serious and related AE with the use of nimotuzumab was 1.3%. Most of the related AEs were mild and moderate, and the most frequent AEs were diarrhea, chills, and tremors. New diagnosed patients who received nimotuzumab concurrent with chemotherapy and radiotherapy reached a median OS of 12.2 months (95% CI, 6.9-17.5) and 12- and 24-month survival rates of 51.0% and 17.0%, respectively. Median PFS was 7.8 months (95% CI, 6.2-9.5), and 12- and 24-month PFS rates were 39.3% and 11.2%, respectively. A favorable evolution of the general state of health (p=0.03) was obtained from the beginning of treatment until month 12, with a significant reduction in the appearance of nausea (p=0.009), insomnia (p=0.04), constipation (p=0.04), eating difficulties (p=0.0006), and choking when swallowing (p=0.0001), but increased in dysphagia (p=0.02). Conclusions: The administration of nimotuzumab was safe in the real-world setting. New diagnosed patients that received nimotuzumab concurrent with chemotherapy and radiotherapy reached a higher overall and progression-free survival and better quality of life than the rest of the patients. Trial registration is RPCEC00000215 (Cuban Registry of Clinical Trials; https://registroclinico.sld.cu/en/home). It is registered prospectively on June 30, 2016.

Eficacia y seguridad clínica del itolizumab en fase de inducción en pacientes con psoriasis grave / Efficacy and clinical safety of Itolizumab in the induction phase in patients with severe psoriasis

Introducción: La psoriasis, enfermedad inflamatoria sistémica de la piel, tiene consecuencias adversas serias para el bienestar físico, mental y social de las personas; sus tratamientos son costosos y con marcados efectos adversos. El itolizumab, anticuerpo monoclonal anti CD6 humanizado, actúa como inmunomodulador de las células T y desempeña un importante papel en su patogénesis. Objetivo: Evaluar la eficacia y la seguridad clínica del itolizumab en 80 pacientes con psoriasis vulgar grave. Métodos: Se realizó un programa de uso clínico expandido, promovido por el Centro de Inmunología Molecular. La respuesta clínica se midió por el índice de gravedad y área de afectación de psoriasis, y para la eficacia se conjugaron estos elementos con los de seguridad, mediante un análisis clínico complementario de los datos generados durante la fase de inducción. Se emplearon como medidas de resumen los números absolutos, el porciento, el promedio y estadísticas de asociación: las pruebas de correlación de de Pearson, de Friedman y la prueba de Lambda. Resultados: El análisis del área de afectación de psoriasis arrojó un rápido y sostenido descenso de sus valores; prevalecieron los eventos adversos relacionados con la administración del producto en investigación, de aparición inmediata, ligeros, muy probables y no serios. Conclusiones: El itolizumab es seguro y eficaz en el 96 por ciento de los pacientes psoriásicos graves durante los esquemas de inducción(AU)

Introduction: Psoriasis, systemic inflammatory skin disease, has serious adverse consequences for the physical, mental and social well-being of people; its treatments are expensive and with marked adverse effects. Itolizumab, a humanized anti-CD6 monoclonal antibody, acts as an immunomodulator of T cells and plays an important role in its pathogenesis. Objective: To evaluate the efficacy and clinical safety of itolizumab in 80 patients with severe psoriasis vulgaris. Methods: An expanded clinical use program was carried out, promoted by the Molecular Immunology Center. The clinical response was measured by the severity index and area of psoriasis involvement and for effectiveness these elements were combined with safety, through a complementary clinical analysis of the data generated during the induction phase. Absolute numbers, percent and average and association statistics such as Pearson's correlation tests or Lambda's test were used as summary measures. Results: The area of psoriasis involvement analysis showed a rapid and sustained decrease in its values; adverse events related to the administration of the product under investigation prevailed, light onset, very probable and not serious. Conclusions: Itolizumab is safe and effective in 96 percent of severe psoriatic patients during the induction phase(AU)

Aplicación de productos inmunoterapéuticos en ensayos clínicos oncológicos en Santiago de Cuba / Implementation of immunotherapeutical products in cancer clinical trials in Santiago de Cuba

Se realizó un estudio descriptivo y retrospectivo sobre la conducción de ensayos clínicos durante 23 años en Santiago de Cuba, con el objetivo de describir la aplicación de 3 productos inmunoterapéuticos (CIMAher-Nimotuzumab, CIMAvax-EGF y Vaxira-Racotumomab) para el tratamiento de pacientes con cáncer en hospitales y policlínicos de la provincia. Se revisaron los informes finales de dichos ensayos, así como la información disponible del centro promotor desde 1992 hasta 2015. Se ejecutaron 20 protocolos de ensayos clínicos por 500 investigadores de 25 especialidades, distribuidos en 4 hospitales de la provincia y 2 se extendieron a 4 áreas de atención primaria de salud. Se concluyó que la aplicación de estos productos inmunoterapéuticos contribuyó al registro sanitario de estos, lo cual enriqueció el arsenal terapéutico para los afectados por cáncer en Santiago de Cuba, con un elevado impacto social

A retrospective descriptive study on the presentation of clinical trials was carried out during 23 years in Santiago de Cuba, with the objective of describing the implementation of 3 immunotherapeutical products (CIMAher-Nimotuzumab, CIMAvax-EGF and Vaxira-Racotumomab) for the treatment of patients with cancer in hospitals and polyclinics from the province. The final reports of each clinical trial and the available information of the promoter center were reviewed from 1992 to 2015. Twenty protocols of clinical trials were implemented by 500 investigators of 25 specialties distributed in 4 hospitals of the province and 4 primary health care areas, where 2 clinical trials in patients with lung cancer were carried out. It was concluded that the implementation of these immunotherapeutical products contributed to the health registration of them, enriching the therapeutic arsenal for the treatment of patients with cancer in Santiago de Cuba, with a high social impact

Modificación del conocimiento y desempeño de los profesionales sobre la gestión de la seguridad del producto en ensayos clínicos / Modification to knowledge and professionals performance on the management of product security in clinical trials

Se realizó una intervención educativa en 19 profesionales, pertenecientes a 2 policlínicos de Santiago de Cuba, quienes participaron en la conducción de ensayos clínicos con productos del Centro de Inmunología Molecular, desde septiembre del 2013 hasta igual mes del 2014, con vistas a evaluar el nivel de sus conocimientos y desempeño sobre la gestión de la seguridad del producto, a partir de una capacitación sobre el tema. Antes y después de la capacitación se aplicó una encuesta de conocimientos y se midió un indicador para cada variable de desempeño identificada. Se establecieron estándares para cada indicador teniendo en cuenta su relevancia y los requisitos reguladores vigentes. Se empleó el test de McNemar para evaluar la significación de los cambios. Se obtuvo una modificación satisfactoria de los conocimientos (84,2 %) y los indicadores de desempeño mejoraron en más de 30 %, pero no alcanzaron el estándar propuesto.

An educational intervention was carried out in 19 professionals, belonging to 2 polyclinics from Santiago de Cuba who participated in carrying out clinical trials with products of the Molecular Immunology Center, from September, 2013 to the same month of 2014, with the aim of evaluating the level of their knowledge and performance on the management of the product security, from a training on the topic. Before and after the training a survey of knowledge was applied, and an indicator for each identified pèrformance variable was measured. Standards were stablished for each indicator keeping in mind their relevance and the effective regulating requirements. McNemar test was used to evaluate the significance of changes. A satisfactory modification of the knowledge was obtained (84.2%) and the performance indicators improved in more than 30%, but they didn't reach the proposed standard.

Estimación de la comprensión alcanzada por los sujetos de investigación clínica durante la obtención del consentimiento informado / Estimate of the understanding reached by individuals from clinical investigation when obtaining the informed consent

Se realizó un estudio descriptivo y transversal de 51 pacientes incluidos en ensayos clínicos efectuados en la provincia de Santiago de Cuba, de enero a diciembre del 2012, a fin de conocer la comprensión alcanzada por estos en cuanto a la información que le proporcionaron durante el proceso de consentimiento informado. A tales efectos, se aplicó un cuestionario estructurado y se definió la comprensión mediante 3 categorías, para luego correlacionarla con el nivel escolar del sujeto y la metodología de aplicación del consentimiento. Pudo concluirse que la mayoría de los participantes en los ensayos clínicos con productos del Centro de Inmunología Molecular, recibían la información requerida en el proceso de consentimiento informado, y que el nivel de escolaridad de los sujetos y la metodología adecuada para la aplicación del consentimiento informado, determinan una mayor comprensión de los elementos de la investigación.

A descriptive and cross-sectional study of 51 patients included in clinical trials made in Santiago de Cuba was carried out from January to December, 2012, in order to know the understanding reached by them regarding the information which they received during the process of informed consent, for which a structured questionnaire was applied and was the understanding was defined by means of 3 categories, correlating it with the person's school level and the methodology for applying the consent. It could be concluded that most of the participants in the clinical trials with products of the Center for Molecular Immunology of this province, received the information required in the process of informed consent. The school level of the participants and the appropriate methodology for the application of the informed consent, determine the higher understanding of the investigation.

Modificación de conocimientos sobre medio ambiente en jóvenes del Laboratorio de Anticuerpos y Biomodelos Experimentales / Modification to knowledge of environment in young people from Laboratory of Antibodies and Experimental Biomodels

Se realizó un estudio de intervención educativa para modificar los conocimientos sobre la conservación del medioambiente en 16 jóvenes del Laboratorio de Anticuerpos y Biomodelos Experimentales de Santiago de Cuba, seleccionados mediante un muestreo aleatorio simple desde abril hasta junio del 2008. Para lograr ese objetivo, la población escogida participó en un programa de clases con 4 sesiones de trabajo, luego de las cuales se comprobó que la insuficiente o errónea información que poseían sobre la necesidad de cuidar responsablemente el entorno por su influencia sobre la salud y calidad de vida, fue modificada favorablemente mediante técnicas participativas y discusiones grupales, de modo que hubo una gran diferencia entre lo que sabían antes del estudio y lo que aprendieron en favor del ambiente después de su ejecución.

A study on educational intervention was conducted to modify the knowledge of the environment conservation in 16 young people from Laboratory of Antibodies and Experimental Biomodels in Santiago de Cuba, selected by means of a simple random sampling from April to June, 2008. To achieve that goal the chosen population participated in a program of classes with 4 working sessions, after which it was verified that their inadequate or erroneous information about the necessity of taking care of the environment responsibly because of its influence on the health and quality of life, was modified favorably by means of participatory techniques and group discussions, so that there was a great difference between what they knew before the study and what they learned in favor of the enviroment after it.