Effectiveness and safety in the management of chronic inflammatory diseases with etanercept and infliximab biosimilars in Colombian patients

Objective: To determine the effectiveness and safety of infliximab and etanercept biosimilar drugs in patients diagnosed with rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and psoriasis in a specialized institution in Colombia, between 2015 and 2019. Methods: A retrospective study in patients treated with infliximab and etanercept biosimilar drugs treated in an institution specializing in the management of rheumatological diseases, to verify the clinimetric indicators of effectiveness and reports of adverse drug reactions. Clinical, sociodemographic, and pharmacological variables were identified over 5 years of follow-up. Results: 207 patients were identified with a mean age of 48.7 ± 15.1 years, 61.4% were women. Of the patients, 58.0% (n = 120) used infliximab and 42.0% (n = 87) etanercept. It was found that 46 (22.2%) patients had adverse drug reactions. At the end of the observation period, 61.6% (n = 72) of the patients with RA had achieved control of the disease (mild activity or remission), and 57.9% (n = 117) had problems with access to and persistence with therapy. Conclusion: In a group of patients treated in Colombia, the biosimilars of infliximab and etanercept showed proportions of effectiveness and safety comparable to the reference drugs, but lack of adherence to treatment was quite common.

Objetivo: Determinar la efectividad y la seguridad de medicamentos biosimilares de infliximab y etanercept en pacientes con diagnóstico de artritis reumatoide, espondilitis anquilosante, colitis ulcerativa y psoriasis en una institución especializada de Colombia, entre los arios 2015 y 2019. Métodos: Estudio retrospectivo, en pacientes tratados con infliximab y etanercept biosimilares, atendidos en una institución especializada en el manejo de enfermedades reumatológicas, para verificar los indicadores clinimétricos de efectividad y reportes de reacciones adversas medicamentosas. Se identificaron variables clínicas, sociodemográficas y farmacológicas durante cinco años de seguimiento. Resultados: Se identificaron 207 pacientes, con una edad media de 48,7 ± 15,1 años, el 61,4% de los cuales eran mujeres. El 58% (n = 120) de los pacientes utilizó infliximab y el 42% (n = 87) etanercept. Se encontró que 46 (22,2%) pacientes presentaron reacciones adversas al medicamento. Al final del periodo de observación, un 61,6% (n = 72) de los pacientes con AR había alcanzado el control de la enfermedad (actividad leve o remisión) y, en general, el 57,9% (n = 117) tuvo problemas de acceso y persistencia a la terapia. Conclusión: En un grupo de pacientes tratados en Colombia, los biosimilares de infliximab y etanercept mostraron proporciones de efectividad y seguridad comparables a los medicamentos de referencia, pero fue bastante común la falta de adherencia al tratamiento.

Frequency of anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus / Frecuencia de los anticuerpos anticitoplasma de neutrófilo en pacientes con lupus eritematoso sistémico

ABSTRACT Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with SLE exhibit multiple serum autoantibodies, including anti-neutrophil cytoplasmic antibodies (ANCAs). There are two main techniques to detect ANCAs: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). In this study, an attempt was made to determine the frequency and clinical associations of ANCAs in patients with SLE. Methods: A cross-sectional study was conducted in a tertiary care hospital in Colombia that included 74 patients with SLE. The presence of ANCAs was assessed using IIF with ethanol-fixed slides, and ELISA was used to detect antibody specificities for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. Results: Of the 74 patients with SLE evaluated, 60 (81.1%) of them were ANCA-positive by IIF. By contrast, only one patient showed specificity for PR3-ANCA by ELISA. The relevance of ANCA positivity by IIF and clinical and serological features was significant for renal involvement (p = .0174), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p = .0308). Conclusion: ANCAs are common in the serum of patients with SLE, as detected by ethanol-fixed slides with IIF staining. However, detection of specificity to PR3 and/or MPO is rare, thus highlighting the importance of detecting these autoantibodies by different techniques.

RESUMEN Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune sistémica. Los pacientes con LES muestran múltiples autoanticuerpos séricos, incluyendo los anticuerpos anticitoplasma de neutrófilo (ANCA, por sus siglas en inglés). Existen 2 técnicas principales para la detección de ANCA: inmunofluorescencia indirecta (IFI) y ensayo por inmunoadsorción ligado a enzimas (ELISA). En este estudio nuestro objetivo fue determinar la frecuencia y las asociaciones clínicas de los ANCA en pacientes con LES. Métodos: Realizamos un estudio transversal de 74 pacientes con LES en un hospital de alta complejidad de Colombia. La presencia de ANCA se evaluó por IFI, utilizando láminas con fijación de etanol, y con ELISA para determinar las especificidades para mieloperoxidasa (MPO)-ANCA y proteinasa 3 (PR3)-ANCA. Resultados: Fueron evaluados 74 pacientes con LES, 60 (81,1%) de ellos fueron positivos para ANCA. Por el contrario, solo un paciente mostró especificidad para PR3-ANCA por ELISA. La relación entre la positividad para ANCA por IFI y las características clínicas y serológicas fue estadísticamente significativa para compromiso renal (p = 0,0174) y para el índice de actividad de la enfermedad (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) (p = 0,0308). Conclusiones: Los ANCA detectados mediante fijación con etanol por técnicas de IFI, son comunes en pacientes con LES. Sin embargo, la detección de especificidades para PR3 o MPO es rara; se destaca la importancia de la evaluación de estos autoanticuerpos mediante diferentes técnicas.

Annual Report on External Quality Assessment of Immunoassay Testing in Korea (2013) / 임상검사와정도관리

Two external quality assessment trials were conducted on 13 test proteins spanning 4 test categories, in 2013. The first trial was initiated on May 6, 2013, and the second trial of immunoassay tests was conducted on November 12, 2013. The trials analysed tumour markers, thyroid hormones, bone marker carboxy-terminal collagen crosslinks (CTX), and the cardiac marker troponin (troponin T [Tn-T] or troponin I [Tn-I]) used in standard immunoassay testing. Three new markers, i.e., thyroglobulin, CTX, and Tn-T/Tn-I were introduced in 2013 to replace 5 existing marker immunoproteins (immunoglobulin G, immunoglobulin M, immunoglobulin A, complement (C)3, and C4). External quality surveys of 13 immunoassay test items were conducted with the aid of 8 control materials. The tested markers included 6 tumour markers (alpha-fetoprotein, carcinoembryonic antigen, carcinoma antigen 125, carbohydrate antigen 19-9), human chorionic gonadotrophin, and prostate specific antigen), 5 thyroid markers (thyroid hormone 3 [T3], T4, thyroid stimulating hormone, free T4, and thyroglobulin), and 1 bone resorption marker CTX. The newly adopted cardiac marker troponin was also included in this study. Five homemade pooled sera and 3 commercial sera were used as the control sera. The thyroid hormones, novel bone marker CTX, and troponin controls were analysed using the MAS Tri-point Liquimmune level 3 (Medical Analysis System, Inc., USA), Elecsys PreciControl Varia, and Elecsys PreciControl Troponin (Roche, Germany), respectively. The external quality assessment was analyzed by the Immunoassay Subcommittee in 685 institutions in the first trial survey (response rate 97.9%) and 678 institutions in the second survey (95.9%). A consistent improvement was observed in the quality of the participating laboratories, particularly in the peer group results. In addition, three new immunoassay markers, thyroglobulin, CTX, and Tn-T/Tn-I, were introduced to the standard assay systems by the Immunoassay Subcommittee.

Annual Report on External Quality Assessment in Immunoassay in Korea (2009) / 임상검사와정도관리

Two trials with 15 test items of external quality assessment survey were performed in 2009. The test items were constituted three immunoassay categories, i.e., tumor markers, thyroid hormones and immunoproteins (IgG, IgM, IgA, C3 and C4). Fifteen test items commonly used in clinical laboratories and performed by immunoassay method were surveyed as scheduled. The number of participated laboratory of external quality assessment for Immunoassay Subcommittee were 494 institutions in the first trial survey and 519 institutions in the second survey. All of the fourteen control materials consisted of 12 home-made pooled sera and 2 commercial control sera (Liquimmune(R), Liquid Assayed Immunoassay Control, Microgenics Co, USA) were used for the two trials in 2009 survey. The results are summarized as follows. 1. Laboratories participating in external quality control program of immunoassay were 494 and 519 laboratories and the response rate were 97.6% and 98.3% in 2009. 2. Chemiluminiscence immunoassay autoanalyzers were most commonly used for immunoassay testing in the clinical laboratories for detecting tumor markers and hormones. 3. Stability tests of home-made control materials were performed and confirmed the CV values were in acceptable ranges. 4. Workshops titled "National health examination for tumors" and "Standardization and harmonization of laboratory tests" were held on September 4, 2009 and December 16, 2009 in cooperation with Annual Autumn Academic Conferences of Clinical Laboratory and Quality Control, and Immunoserology Subcommittee, respectively. The quality of the participating laboratories seems to be continuously improved. And, this year, new sixty eight laboratories were participated to our Immunoassay Subcommittee.

Annual Report on External Quality Assessment of Immunoassay Subcommittee in Korean Clinical Laboratory Survey (2008) / 임상검사와정도관리

Two trials of external quality assessment were performed in 2008. The first and the second trials assessed by three test categories, i.e., tumor markers, thyroid hormones and immunoproteins (IgG, IgM, IgA, C3 and C4). Fifteen test items using immunoassay method were surveyed as scheduled. The number of participated laboratory of external quality assessment for Immunoassay Subcommittee were 437 institutions in the first trial survey and 476 institutions in the second survey.Fourteen control materials consisted of 12 home-made pooled sera and 2 commercial control sera (Liquimmune(R), Liquid Assayed Immunoassay Control, Microgenics Co, USA) were used. The results are summarized as follows. 1. Laboratories participating in external quality control program of immunoassay were 437 and 476 laboratories and the response rate were 94.6% and 98.7% in 2008. 2. Chemiluminiscence immunoassay autoanalyzers were most commonly used for immunoassay testing in the clinical laboratories for detecting tumor markers and hormones. 3. Some analyzers of a few test items showed variations of the test results of the same control material probably due to personal factors of the institution. 4. Workshops titled "Quality control of Immunoassay" and " Quality control of tumor markers" were held on September 5, 2008 and December 3, 2008 in cooperation with Annual Autumn Academic Conferences of Clinical laboratory and Quality Control and Immunoserology Subcommittee. The quality of the participating laboratories seems to be thought being continuously improved. And, this year, about 51 laboratories are newly participated to our Immunoassay Subcommittee.

Annual Report on External Quality Assessment of Immunoassay Subcommittee in Korean Clinical Laboratory Survey (2005) / 임상검사와정도관리

Three trials of external quality assessment were performed in 2005. The first and the second trials were assessed by 14 test items including tumor markers, hormones and immunoproteins and the third trial was intended only for five items of immunoproteins, i.e. Immunoglobulin G (IgG), IgM, IgA, Complement 3 (C3) and C4. Fourteen test items of immunoassay method including 5 tumor markers, 4 hormones and 5 imunoproteins were surveyed. The response rate of external quality assessment for Immunoassay Subcommittee were 94.4% ~ 95.0% in this year. Ten control materials of the first and second trials were consisted of 8 home-made pooled sera and 2 commercial control sera (LyphoCheck, BioRad, USA and Randox, Randox Ltd., UK). And, for the third trial we used the 05-S-4 specimen of the Immunoserology Subcommittee control material. The results are summarized as follows. 1. Laboratories participating in external quality control program of Immunoassay Subcommittee were 305 laboratories and the response rate were 94.4% and 95.0% in 2005. 2. Autoanalyzers based on enhanced or improved enzyme/chemiluminiscence imunoassay were mostly used in the field of immunoassay testing. 3. A new reporting system which uses the internet web site was introduced in this year from the second trial of external quality survey. 4. Some test items show big variations of the test results of the same control material according to autoanalyzer and reagents. The quality of the participating laboratories seems to be improved step by step. And, the new methods of reporting system and statistic analyses introduced this year were considered to get a good reputation from the member institutes for the surveillance systems.

Anemia hemol¡tica autoinmune caliente. Estudio de 183 pacientes / Warm reactive autoimmune hemolytic anemia. Study of 183 cases

Se diagnosticaron 183 pacientes con AHAC, 125 adultos y 58 ni¤os, en el Instituto de Hematolog¡a e Inmunolog¡a de Ciudad de La Habana, Cuba, entre enero de 1990 y septiembre de 1999. La presencia de IgG y de C3 en los hemat¡es fue el patr¢n más com£n y en menores frecuencias se observaron autoanticuerpos de los isotipos IgA e IgM. Se encontr¢ un incremento significativo del patron C3 en los ni¤os en relaci¢n con los adultos y en los ni¤os con AHAC idiopática con respecto a los de AHAC secundaria. En los pacientes con hem¢lisis grave predominaron las combinaciones de IgG y C3 asociado a IgA e IgM. Se detect¢ un 15 por ciento y un 3 por ciento de aloinmunizaci¢n eritrocitaria en los pacientes adultos y pediátricos, respectivamente. No se demostraron diferencias en los patrones de inmunoprote¡nas en los hemat¡es entre los pacientes adultos y pediátricos, excepto un aumento de la frecuencia del patr¢n C3 en estos £ltimos. La hem¢lisis grave se asoci¢ a la presencia de m£ltiples clases de autoanticuerpos.

Study on relationship between hemocompatibility and protein adsorption for DLC / 生物医学工程学杂志

In this paper, the adsorption of human serum albumin(HSA), human serum fibrinogen (HFG) and human serum immunoglobin(IgG) on diamond like carbon film(DLC) has been studied in comparison with diamond film (DF) and graphite. The isothermal adsorption of the protein solution with single component and the competitive adsorption of binary protein system have been investigated by radio isotope 125I labelling method. Results showed that (1) the adsorptive amounts of three proteins on three material surfaces are all increased with the increasing concentration of protein solution, then the adsorption tends to reach an equilibrium; (2) the adsorptive amounts of three protein on graphite far exceed that on DLC and DF; (3) the adsorptive amounts of HSA on DLC are more than that on DF, while the adsorptive amounts of HFG and IgG on DF and graphite are apparently more than that on DLC; (4) the differences among the adsorptive amounts of three proteins on DLC are small, but adsorptive amounts of HFG and IgG on DF and graphite are much more than that of HSA; (5) the relative competitive adsorption ability of three proteins on DF and graphite is HFG > IgG > HSA, but on DLC, the sequence is HFG approximately HSA > IgG. Comparing with HSA, HFG has no apparent competitive adsorption superiority to DLC. These results indicate that there is no apparent difference for the adsorption of three human serum proteins on DLC, but the adsorption of HFG and IgG on DF and graphite takes precedence of various degrees. It probably makes a rational explanation for the result of hemocompatibility tests in vitro that DLC is superior to, DF and graphite.

Prognostic Significance of the Tall Cell Variant of Papillary Thyroid Carcinoma: Expression of p53, bcl-2 & Leu-M1 proteins

Papillary carcinoma of the thyroid is a well differentiated neoplasm and usually has a good prognosis. However, a subset of morphologically distinct papillary carcinoma has bad prognoses. The tall cell variant of papillary carcinoma (TCPC), characterized by tall columnar cells with a height at least twice the width, is the one of these. In order to differentiate TCPC from usual papillary carcinoma (UPC) in terms of prognosis, we performed immunohistochemical studies for the expression of p53, bcl-2 and Leu-M1 proteins in 25 cases of TCPC, 26 cases of UPC and 14 cases of poorly differentiated, solid type papillary carcinoma (SPC) with an analysis of clinical parameters. The nuclear expression of p53 was noted in one case each of UPC and TCPC. The cytoplasmic p53 expression of TCPC, UPC, and SPC was observed in 17/25 cases (68%), 14/26 cases (54%), 3/14 cases (21%), respectively. bcl-2 expression was 19/25 cases (76%), 18/26 cases (69%), 5/14 cases (36%), and that of Leu-M1 was 21/25 cases (84%), 18/26 cases (69%), 4/14 cases(29%), respectively. There were no statistical significance in the expression of those immunoproteins among these three groups (p>0.05). The p53 protein was consistently expressed in the cytoplasm rather than nucleus in this study and was very well correlated to bcl-2 positivity (p0.05). In conclusion, TCPC can not be separated from UPC as a distinct entity in this study and the cytoplasmic expression of p53 protein provides another mechanism of p53 inactivation in tumorigenesis of the thyroid papillary carcinoma, possibly by bcl-2 related mechanism.

Inmunofijación: complemento de la inmunoelectroforesis en el estudio de las inmunoglobulinas monoclonales / Inmunofixation: complement of inmunoelectroforesis in the study of monoclonal inmunoglobulins

E método de inmunofijación simplificado ha resultado útil en la identificación de anormalidades monoclonales no caracterizadas por inmunoelectroforesis. Este métodos permitió resolver 3 de 19 muestras de suero procesados, con una alteración monoclonal no caracterizada completamente por inmunoelectroforesis. Basados en estos resultados y en la revisión de la literatura, se propone el método de inmunofijación simplificado para la identificación y caracterización de anormalidades monoclonales, cuando éstas no son satisfactoriamente clasificadas por inmunoelectroforesis