RESUMO
OBJECTIVES: To describe the rate of infliximab discontinuation and the causes of this event in a population of rheumatoid arthritis patients. PATIENTS AND METHODS: Rheumatoid arthritis patients from an out-patient private center treated with infliximab (at least 2 consecutive doses) were retrospectively studied. The infliximab discontinuation rate was examined by the Kaplan-Meier survival method. Variables associated with infliximab discontinuation were analyzed by univariable and multivariable Cox proportional hazards regression analyses. RESULTS: Seventy-seven patients treated with infliximab between August 2000 and December 2006 were identified; of them, 33 (43%) discontinued this drug. The cumulative discontinuation rate was of 23%, 35%, and 43% at 12, 24, and 36 months, respectively. Causes of discontinuation were drug-related adverse reactions (41%), financial constraints (15%), lack of efficacy (12%), and others (32%). Variables independently associated with infliximab discontinuation were the number of tender joints on an average during infliximab treatment [hazard ratio (HR) = 1.17, 95% confidence interval (CI) 1.05-1.31; P = 0.005] and the occurrence of any adverse reaction attributed to infliximab (HR = 2.86, 95% CI 1.37-7.19; P = 0.026), whereas having full pharmacy coverage for infliximab (HR = 0.32, 95% CI 0.13-0.79, P = 0.014) was protective. CONCLUSION: Forty-three percent of patients discontinued infliximab at 3 years; most of them because of adverse reactions and financial constraints. Rheumatologists should be aware that those patients with more active disease were also at higher risk of discontinuing infliximab.
Assuntos
Anticorpos Monoclonais , Antirreumáticos , Artrite Reumatoide/tratamento farmacológico , Medicina Clínica/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/economia , Antirreumáticos/efeitos adversos , Antirreumáticos/economia , Argentina , Artrite Reumatoide/economia , Contraindicações , Feminino , Custos de Cuidados de Saúde , Humanos , Infliximab , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To address participants' knowledge of informed consent and to explore whether knowledge level is related to clinical trial satisfaction. METHODS: One hundred and fourteen patients enrolled in three ongoing randomized controlled trials of osteoarthritis and rheumatoid arthritis were asked to complete a mailed form. The survey was related to aspects of the informed consent process: quality of information given during the informed consent process, participants' self perception of knowledge, objective evaluation of participants' knowledge and participants' overall trial satisfaction. These four aspects were categorized as high, intermediate or low. Correlation between participants' knowledge and satisfaction was measured using the Spearman's Rho test and variables associated with knowledge by standard univariable analyses. A p value< or =0.05 was considered significant. RESULTS: One hundred and five participants answered the questionnaire. The quality of information given during the informed consent process was rated as being high by 81% participants, intermediate by 15.2% and low by 3.8%. Fifty-one percent of the participants believed they had a good level of knowledge, but, objective evaluation qualified as high in only 14.3% of them. Overall trial satisfaction was high in 95% of the participants. No significant correlation was found between knowledge and satisfaction (r=0.16; p=0.086). Age was negatively associated with a higher level of knowledge (48 vs. 58 years old, p=0.008). CONCLUSIONS: We found a lack of correlation between satisfaction and knowledge in clinical trials participants. During a randomized controlled trial the investigator should consider encouraging activities to improve not only participants' satisfaction, but also their level of knowledge.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Argentina , Feminino , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artropatias/tratamento farmacológico , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Assistência Ambulatorial , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Proteína C-Reativa/análise , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVES: To study patient's follow-up after finishing participation in randomized clinical trials (RCTs), and to identify factors associated with loss to follow-up (FU). PATIENTS AND METHODS: Medical charts of 212 rheumatoid arthritis (RA) and osteoarthritis (OA) patients from a rheumatological out-patient center were analyzed. Loss to FU was considered when patients did not return to their regular appointments within the first year after finishing their participation in an RCT assessing anti-cyclooxygenase-2 non-steroidal anti-inflammatory drugs (anti-COX-2 NSAIDs). Mann-Whitney U-test, chi2 test and Wilcoxon test were performed as appropriate. Logistic regression was performed to identify factors which might be related to loss to FU. A survey was conducted to obtain lost to FU patients' opinions. p values less than 0.05 were considered significant. RESULTS: The mean frequency of patients' visits in the year before enrollment in an RCT was 3.73 SD 2.06, and during the year after participation was 2.6 SD 1.96 (p<0.0001). Fifty patients (23.6%) did not return to their usual rheumatologic visit. On multivariate analysis, the number of daily tablets of study medication (odds ratio (OR)=2.64, 95% confidence interval (CI) 1.1 to 6.3) and the frequency of clinical visits (OR=0.56, 95% CI 0.37 to 0.85) were associated with loss to FU (p<0.008). Lost to FU patients' opinions did not support these findings. CONCLUSIONS: After participating in a RCT assessing anti-COX-2 NSAIDs, many patients return with less frequency, or do not return at all to their regular rheumatologic visit. Although a high number of tablets of the investigational drug and a low frequency of protocol visits may be contributors to patient loss to FU, investigators should consider that personal situations not related to the RCTs may also influence patients' return to consultation in the private setting.
Assuntos
Pacientes Desistentes do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Artrite Reumatoide/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Análise Multivariada , Osteoartrite/tratamento farmacológico , Relações Médico-Paciente , Estudos Retrospectivos , Fatores de Risco , Estatísticas não ParamétricasRESUMO
The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9
) patients could decrease the doses of corticosteroids, 15/43 (34.8
) decreased the doses of antiinflammatory drugs and 12/34 (35.3
) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.
RESUMO
OBJECTIVE: To evaluate the influence of the weather in Cordoba City, Argentina, on pain in patients with rheumatic pain; to correlate different climate variables with the patients' impression of weather sensitivity; and to assess correlations between pain and climate conditions on 5 days preceding and following painful episode. METHODS: Self-reported questionnaires to assess the presence and features of spontaneous daily pain during one year (1998) were completed by 151 outpatients with osteoarthritis (OA) (n = 52), rheumatoid arthritis (RA) (n = 82), and fibromyalgia (FM) (n = 17) and 32 healthy subjects. Data were correlated with daily temperature, atmospheric pressure, and relative humidity obtained during the same period. Only p values < 0.001 were considered significant. RESULTS: Low temperature, high atmospheric pressure, and high humidity were significantly correlated with pain in RA (r = -0.30, r = 0.34, r = 0.23, respectively; p < 0.001); in OA, pain correlated with low temperature and high humidity (r = -0.23, r = 0.24; p < 0.001); in FM, with low temperature and high atmospheric pressure (r = -0.255, r = 0.22; p < 0.001) and no correlation was found in controls. Patients self-described as being weather sensitive correlated only with high humidity (r = 0.45; p < 0.001). There was no better correlation with climate variables, except for humidity, 5 days before or after the day of the painful episode. CONCLUSION: These results support the belief that weather influences rheumatic pain, albeit in different ways depending on the subjacent pathology and subjective weather sensitivity. This influence may not depend on weather conditions of the previous or following days, indicating that climate would not be a pain predictor and vice versa.
Assuntos
Artrite Reumatoide/complicações , Fibromialgia/complicações , Osteoartrite/complicações , Dor/etiologia , Tempo (Meteorologia) , Idoso , Argentina , Artrite Reumatoide/fisiopatologia , Feminino , Fibromialgia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Dor/fisiopatologia , Medição da Dor , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
El cartílago articular es un tejido paucicelular, con colágeno y proteoglicanos en la matriz extracelular. Su degradación es función de los sinoviocitos, que segregan metaloproteasas que catabolizan a los proteoglicanos. Se distinguen los sinoviocitos A o macrofágicos y los sinoviocitos B o fibroblásticos. La destrucción de proteoglicanos puede ser LT- dependiente o independiente. Nuestro objetivo fue estudiar ex vívo el rol de los sinoviocitos, sin la influencia del sistema inmune. Líquido sinovial de pacientes de ambos sexos, 70ñ2años, con OA(6) y AR(6), vírgenes de tratamiento, se centrifugó 30 minutos a 1500 g, para aislar sinoviocitos. El sedimento se incubó 6 hs en medio Dulbecco-Eagles, con 26 mM de HEPES Gibco, NaHCO3 ( 0.5g/l), glutamina (2 mM), estreptomicina (100mg/l), penicilina (1 U/ml) y anfotericina B (2.5mg/l). Identidad y viabilidad celulares se determinaron con técnicas citopatológicas. Las muestras control provinieron de artritis traumática o patología osteoarticular no-inflamatoria. Con anticuerpos monoclonales anti-MMPs(10mg/ml), previo bloqueo de producción de proteínas inespecíficas con albúmina sérica bovina, se midió actividad colagenasa (MMP-1) antes y después de incubar con ELISA-doble-sandwich. Con streptavidin-peroxidasa se desarrolló color y por absorbancia a 410 nm, se leyó la complejación de los anticuerpos marcados. La secreción de MMP-1 por sinovio-citos AR fue 1373ñ115 ng/ml. Con 6 hs de incubado aumentó hasta 2143ñ132ng/l (-56 por ciento)(p<0.0001), probablemente por la hipercelularidad. Los sinoviocitos OA secretaron 276 ñ 23 ng/ml , y 542 ñ 47 ng/ml tras la incubación (96 por ciente)(p<0.001). Hay paralelismo entre la producción de MMP-1 y la observación microscópica. Sinoviocitos con abundante citoplasma corresponden a altos niveles de enzima. La baja secreción de MMPs responde a escasa población celular y núcleos picnóticos. Aunque en AR la producción de MMPs fue 4.6 veces mayor que en OA, en cambio el incremento porcentual tras la incubación fue casi el doble en OA que en AR. Esos resultados confirman que la producción enzimática varía con la inflamación, que es mayor en los procesos agudos, y que la incubación de sinoviocitos permite detectar cambios patológicos locales
Assuntos
Humanos , Artrite Reumatoide/enzimologia , Líquido Sinovial/enzimologia , Metaloproteinase 1 da Matriz/biossíntese , Osteoartrite/enzimologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção EnzimáticaRESUMO
El cartílago articular es un tejido paucicelular, con colágeno y proteoglicanos en la matriz extracelular. Su degradación es función de los sinoviocitos, que segregan metaloproteasas que catabolizan a los proteoglicanos. Se distinguen los sinoviocitos A o macrofágicos y los sinoviocitos B o fibroblásticos. La destrucción de proteoglicanos puede ser LT- dependiente o independiente. Nuestro objetivo fue estudiar ex vívo el rol de los sinoviocitos, sin la influencia del sistema inmune. Líquido sinovial de pacientes de ambos sexos, 70ñ2años, con OA(6) y AR(6), vírgenes de tratamiento, se centrifugó 30 minutos a 1500 g, para aislar sinoviocitos. El sedimento se incubó 6 hs en medio Dulbecco-Eagles, con 26 mM de HEPES Gibco, NaHCO3 ( 0.5g/l), glutamina (2 mM), estreptomicina (100mg/l), penicilina (1 U/ml) y anfotericina B (2.5mg/l). Identidad y viabilidad celulares se determinaron con técnicas citopatológicas. Las muestras control provinieron de artritis traumática o patología osteoarticular no-inflamatoria. Con anticuerpos monoclonales anti-MMPs(10mg/ml), previo bloqueo de producción de proteínas inespecíficas con albúmina sérica bovina, se midió actividad colagenasa (MMP-1) antes y después de incubar con ELISA-doble-sandwich. Con streptavidin-peroxidasa se desarrolló color y por absorbancia a 410 nm, se leyó la complejación de los anticuerpos marcados. La secreción de MMP-1 por sinovio-citos AR fue 1373ñ115 ng/ml. Con 6 hs de incubado aumentó hasta 2143ñ132ng/l (-56 por ciento)(p<0.0001), probablemente por la hipercelularidad. Los sinoviocitos OA secretaron 276 ñ 23 ng/ml , y 542 ñ 47 ng/ml tras la incubación (96 por ciente)(p<0.001). Hay paralelismo entre la producción de MMP-1 y la observación microscópica. Sinoviocitos con abundante citoplasma corresponden a altos niveles de enzima. La baja secreción de MMPs responde a escasa población celular y núcleos picnóticos. Aunque en AR la producción de MMPs fue 4.6 veces mayor que en OA, en cambio el incremento porcentual tras la incubación fue casi el doble en OA que en AR. Esos resultados confirman que la producción enzimática varía con la inflamación, que es mayor en los procesos agudos, y que la incubación de sinoviocitos permite detectar cambios patológicos locales (AU)
Assuntos
Humanos , Líquido Sinovial/enzimologia , Osteoartrite/enzimologia , Artrite Reumatoide/enzimologia , Metaloproteinase 1 da Matriz/biossíntese , Estudos de Casos e Controles , Ensaio de Imunoadsorção EnzimáticaRESUMO
Desarrolla los más recientes descubrimientos fisiopatológicos, bioquímicos y neuro-humorales de los procesos inflamatorios y actualiza el mecanismos de acción, farmacocinética, interacciones medicamentosas y reacciones adversas de los antiinflamatorios no esteroides (AINES)
Assuntos
Humanos , Inflamação/fisiopatologia , Anti-Inflamatórios não Esteroides/farmacocinética , Artrite Reumatoide/fisiopatologia , Eicosanoides/fisiologia , Neutrófilos/enzimologia , Inflamação/imunologia , Eicosanoides/classificação , Anti-Inflamatórios não Esteroides/efeitos adversosRESUMO
Desarrolla los más recientes descubrimientos fisiopatológicos, bioquímicos y neuro-humorales de los procesos inflamatorios y actualiza el mecanismos de acción, farmacocinética, interacciones medicamentosas y reacciones adversas de los antiinflamatorios no esteroides (AINES)