Long-term drug survival of biological agents in patients with rheumatoid arthritis in clinical practice.

OBJECTIVES: To assess and compare the long-term drug survival (time to drug discontinuation) of biological agents (BA) in patients with rheumatoid arthritis (RA) in clinical practice. Factors associated with discontinuation of BAs were also investigated. METHOD: We conducted an observational longitudinal study of RA patients taking BAs from 1999 to 2013. The primary endpoint was BA discontinuation due to: adverse drug reactions (ADRs), inefficacy, and other causes. Incidence rates of discontinuation (IRs) per 100 patient-years were estimated using survival techniques. Comparisons between BA discontinuation rates and other associated factors were made using Cox regression models. RESULTS: We included 851 courses of BA therapy (1869 patient-years). Adalimumab (33%) was the BA most frequently used, followed by etanercept (24.4%), infliximab, and rituximab. Treatment was suspended in 558 cases [IR 29.8, 95% confidence interval (CI) 27-32]. In the first year of therapy 68% continued on BAs, and after 10 years the retention rate did not exceed 10%. The IR due to inefficacy was 12.1 (95% CI 10.6-13.8) and the IR of ADRs was 13.6 (95% CI 12-15). The unadjusted IR was higher for rituximab than for tumour necrosis factor (TNF) antagonists. In multivariate analysis, infliximab was the BA with the highest risk of discontinuation, compared to adalimumab. Calendar period, taking subsequent courses of BAs, concomitant therapy, and specific comorbidities were also independent factors associated with discontinuation. CONCLUSIONS: After several years of BA treatment in clinical practice, the survival rate was low, mainly as a result of ADRs and inefficacy. We also found differences between the discontinuation rates of BAs and other clinical factors that modify their survival.

Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-modifying anti-rheumatic drugs: a survival analysis.

OBJECTIVES: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. RESULTS: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. CONCLUSIONS: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.

Long-term use of antimalarial drugs in rheumatic diseases.

OBJECTIVES: To evaluate long-term use of antimalarial drugs and to analyse all causes of discontinuation. METHODS: This is a retrospective study of a cohort of rheumatic diseases patients on antimalarials, during a maximum period of 17.5 years. Case was defined as antimalarial treatment discontinuation due to: a) lack of efficacy, b) adverse events, and c) other causes. Survival techniques were used to estimate the incidence rate (IR) per 1,000 patient-years with the 95% Confidence Interval (95% CI) of antimalarial treatment discontinuation. Cox regression models were conducted to evaluate possible associated factors to antimalarial discontinuation. RESULTS: One thousand, two hundred and ninety-one medical records were reviewed, and 778 patients were included. Patients started 869 different courses of treatment, with a total follow-up of 2,263 person-years. The IR of global discontinuation was 204 (95% CI 186-224). Fifty-two per cent of the treatments stopped were related to adverse events, 14% to lack of efficacy; and 34% to other reasons (refusal to take medication, ocular comorbidity, remission, or pregnancy). Adverse events discontinuations were related to non-ophthalmologic reasons in 54.5% (gastrointestinal, neuro-psychiatric, skin problems), and to ophthalmologic adverse events in 45.5%. Nine patients suffered definite presence of antimalarial retinopathy (IR: 3.97 [IC 95%: 2.06-7.62]) and one of them irreversible loss of vision (IR: 0.44 [IC 95%: 0.06-3.12]). Women, increasing age, and chloroquine vs. hydroxychloroquine use, increased the risk of discontinuation due to ophthalmologic adverse events. CONCLUSIONS: Results suggest that antimalarials have a good balance between benefit and risk. However, we noted a number of discontinuations due to both inefficacy and adverse events. The potential for an unusual but serious ophthalmologic toxicity emphasises the importance of close ophthalmologic monitoring.

Differences between rheumatology attending physicians and training residents in the management of rheumatoid arthritis in Spain.

OBJECTIVE: To evaluate the variability in the characteristics and management of rheumatoid arthritis (RA) patients between rheumatology attending physicians and training residents in Spain. METHODS: A retrospective medical record (MR) review was performed in a probabilistic sample of 1379 RA patients from 46 centres distributed in 16 of the 19 autonomous communities (AC) of Spain. RA patients' sociodemographic and clinical characteristics, healthcare resources use, and their single responsible physician's (defined as an identifiable single physician who attended the patient in more than 75% of visits) characteristics were recorded following a standardized protocol. Multivariate analyses were performed to assess differences in the characteristics and management of RA patients between attending physicians and training residents. RESULTS: A total of 1205 RA patients had a single responsible physician and were analysed (nearly 75% women with rheumatoid factor positive and more than 25% with persistent active disease), 49 of whom were followed by training residents and 1156 by attending physicians. In the multivariate analyses, irrespective of patient and disease characteristics, training residents' patients reported more hospital admissions, laboratory tests, and imaging techniques compared to attending physicians. Training residents also less frequently used combined therapy with disease-modifying antirheumatic drugs (DMARDs). CONCLUSION: Training residents and attending physicians differ in RA patients' care. More efforts in training programmes are necessary to guarantee proper RA management and to improve the profile of the future rheumatologists.

Evaluación clínica de los pacientes con artritis reumatoide en España / Clinical evaluation of patients with rheumatoid arthritis in Spain

Fundamento: En los últimos años se han desarrollado instrumentos que permiten evaluar la eficacia clínica de las intervenciones en pacientes con artritis reumatoide (AR). Sin embargo, no hay datos sobre su utilización en la evaluación rutinaria de los pacientes con AR en nuestro país. Objetivo: Analizar los instrumentos utilizados en la evaluación clínica de pacientes con AR en España. Material y métodos: Revisión de 1.379 historias clínicas (HC), seleccionadas aleatoriamente, de pacientes con AR atendidos en 48 servicios de atención especializada de 16 comunidades autónomas. Se realizó una estimación semicuantitativa del número de visitas en dos años en las que se habían utilizado diferentes instrumentos de seguimiento clínico. Resultados: La rigidez matutina y la valoración subjetiva del médico en una escala adjetiva fueron los instrumentos más utilizados (habitualmente o siempre en más del 70% de las HC). El 49,5% de los pacientes tenía al menos un recuento formal de articulaciones dolorosas y tumefactas; el recuento articular más utilizado fue el índice completo del American College of Rheumatology (ACR). La utilización de escalas analógicas visuales (EAV) fue muy infrecuente. Ninguno de los instrumentos de valoración del estado funcional y del estado general de salud fue utilizado habitualmente en la práctica clínica diaria. Conclusiones: El uso de instrumentos cuantitativos en la valoración clínica y el seguimiento de los pacientes con AR en nuestro país es muy escaso, prevaleciendo los instrumentos de seguimiento tradicionales

Background: Several instruments to evaluate the efficacy of clinical interventions in patients with rheumatoid arthritis (RA) have been developed in the last few years. However, there are no data on the utilization of these instruments in the routine evaluation of patients with RA in Spain. Objective: To analyze the instruments used in the clinical evaluation of patients with RA in Spain. Material and methods: The medical records of 1,379 patients diagnosed with RA randomly selected and treated in 48 specialized care units in 16 Autonomous Communities were reviewed. The number of consultations in which several clinical follow-up instruments were employed in a 2-year period was estimated semiquantitatively. Results: The most frequently used instruments (usually or always in > 70% of medical records) were morning stiffness and the physician's overall assessment of disease activity using adjective scales. A total of 49.5% of the patients had at least one formal count of tender and swollen joints and the ACR index was the most commonly used. Visual analogue scales (VAS) were used very infrequently. None of the instruments to evaluate functional ability or overall health status were routinely used in daily practice. Conclusions: The use of quantitative instruments in the clinical evaluation and follow-up of patients with RA is low and traditional instruments of follow-up prevail

Evaluación clínica de los pacientes con artritis reumatoide en España / Clinical evaluation of patients with rheumatoid arthritis in Spain

Fundamento: En los últimos años se han desarrollado instrumentos que permiten evaluar la eficacia clínica de las intervenciones en pacientes con artritis reumatoide (AR). Sin embargo, no hay datos sobre su utilización en la evaluación rutinaria de los pacientes con AR en nuestro país. Objetivo: Analizar los instrumentos utilizados en la evaluación clínica de pacientes con AR en España. Material y métodos: Revisión de 1.379 historias clínicas (HC), seleccionadas aleatoriamente, de pacientes con AR atendidos en 48 servicios de atención especializada de 16 comunidades autónomas. Se realizó una estimación semicuantitativa del número de visitas en dos años en las que se habían utilizado diferentes instrumentos de seguimiento clínico. Resultados: La rigidez matutina y la valoración subjetiva del médico en una escala adjetiva fueron los instrumentos más utilizados (habitualmente o siempre en más del 70% de las HC). El 49,5% de los pacientes tenía al menos un recuento formal de articulaciones dolorosas y tumefactas; el recuento articular más utilizado fue el índice completo del American College of Rheumatology (ACR). La utilización de escalas analógicas visuales (EAV) fue muy infrecuente. Ninguno de los instrumentos de valoración del estado funcional y del estado general de salud fue utilizado habitualmente en la práctica clínica diaria. Conclusiones: El uso de instrumentos cuantitativos en la valoración clínica y el seguimiento de los pacientes con AR en nuestro país es muy escaso, prevaleciendo los instrumentos de seguimiento tradicionales (AU)

Background: Several instruments to evaluate the efficacy of clinical interventions in patients with rheumatoid arthritis (RA) have been developed in the last few years. However, there are no data on the utilization of these instruments in the routine evaluation of patients with RA in Spain. Objective: To analyze the instruments used in the clinical evaluation of patients with RA in Spain. Material and methods: The medical records of 1,379 patients diagnosed with RA randomly selected and treated in 48 specialized care units in 16 Autonomous Communities were reviewed. The number of consultations in which several clinical follow-up instruments were employed in a 2-year period was estimated semiquantitatively. Results: The most frequently used instruments (usually or always in > 70% of medical records) were morning stiffness and the physician’s overall assessment of disease activity using adjective scales. A total of 49.5% of the patients had at least one formal count of tender and swollen joints and the ACR index was the most commonly used. Visual analogue scales (VAS) were used very infrequently. None of the instruments to evaluate functional ability or overall health status were routinely used in daily practice. Conclusions: The use of quantitative instruments in the clinical evaluation and follow-up of patients with RA is low and traditional instruments of follow-up prevail (AU)

Hematuria masiva en una paciente con artritis reumatoide / Massive hematuria in a patient with rheumatoid arthritis

Describimos el caso de una paciente de 61 años diagnosticada de artritis reumatoide. Desarrolló hematuria masiva con expulsión de coágulos sanguíneos; una biopsia de la mucosa vesical reveló amiloidosis secundaria. La amiloidosis secundaria sintomática de la vejiga es muy rara. Solamente se han descrito 22 casos en la bibliografía. La mayoría de estos casos tenía enfermedades reumáticas, más frecuentemente artritis reumatoide (AR) y espondilitis anquilosante (EA). Creemos que es necesario tener en cuenta la posibilidad de amiloidosis secundaria de la vejiga cuando el reumatólogo se enfrente a un paciente con artritis reumatoide y hematuria macroscópica (AU)

We describe the case of a 61-year-old woman with a diagnosis of rheumatoid arthritis. She developed massive hematuria with expulsion of blood clots. Biopsy of the vesical mucosa revealed secondary amyloidosis. Symptomatic amyloidosis of the bladder is highly infrequent and only 22 cases have been reported in the literature. Most reported patients had rheumatic disease, especially rheumatoid arthritis and ankylosing spondylitis. The possibility of secondary amyloidosis of the bladder should be suspected in patients with rheumatoid arthritis and gross hematuria (AU)

[Incidence and characteristics of tuberculosis in patients with autoimmune rheumatic diseases]. / Incidencia y características de la tuberculosis en pacientes con enfermedades reumáticas autoinmunes.

OBJECTIVE: To describe the incidence and characteristics of the infection caused by Mycobacterium tuberculosis in patients with autoimmune diseases. PATIENTS AND METHODS: Searching in the database of the department at our institution, all new cases of tuberculosis from 1991 to 2000 were identified in patients with autoimmune diseases; the total follow-up time was calculated as the difference between first and last visits. Time with immunosuppressive drug therapy was obtained for patients with rheumatoid arthritis from a database oriented to the longitudinal follow-up of these patients. The incidence density was calculated as the quotient between the absolute frequency of cases and the sum of individual periods at risk for each subgroup. RESULTS: Fifteen cases of tuberculosis were identified from 3,634 risk patients followed for an accumulated period of 9,795 years (overall incidence 153 per 100,000 patients-year). Fourteen patients were receiving disease-modifying drugs and eleven were receiving corticosteroids at diagnosis. The location of tuberculosis infection was the lung for 33.3% of cases. The incidence by drugs in patients with rheumatoid arthritis was 143 per 100,000 patients-year with methotrexate, 2,703 per 100,000 patients-year with azathioprin, 7,692 per 1,000 patients-year with cyclophosphamide, and 4,878 per 100,000 patients-year for anti-TNFalpha. CONCLUSIONS: Compared with the general population, the incidence density of tuberculosis is increasing in our population, with a higher frequency of extrapulmonary involvement. The incidence density is variable among patients with rheumatoid arthritis depending upon the used drugs.

Incidencia y características de la tuberculosis en pacientes con enfermedades reumáticas autoinmunes / Incidence and characteristics of tuberculosis in patients with autoimmune rheumatic diseases

Objetivo. Describir la incidencia y las características de la infección por Mycobacterium tuberculosis en pacientes con enfermedades autoinmunes.Pacientes y métodos. Se identificaron los casos nuevos de tuberculosis desde 1991 a 2000 en pacientes con enfermedad autoinmune a partir de la base de datos del servicio; se calculó el tiempo total de seguimiento como la diferencia entre la primera y la última visita. El tiempo de tratamiento con fármacos inmunosupresores se obtuvo en pacientes con artritis reumatoide de una base de datos orientada al seguimiento longitudinal de estos pacientes. Se calculó la densidad de incidencia como el cociente entre la frecuencia absoluta de casos y la suma de los períodos individuales de riesgo en cada subgrupo. Resultados. Se identificaron 15 casos de tuberculosis en 3.634 pacientes en riesgo seguidos durante un período acumulado de 9.795 años (incidencia global: 153 por 100.000 pacientes-año).Catorce pacientes estaban recibiendo fármacos modificadores de la enfermedad y once corticosteroides en el momento del diagnóstico. La localización de la infección tuberculosa fue pulmonar en el 33,3 por ciento de los casos. La incidencia por fármacos en pacientes con artritis reumatoide fue de 143 por 100.000 pacientes-año con metotrexato, 2.703 por 100.000 pacientes-año con azatioprina, 7.692 por 1.000 pacientes-año con ciclofosfamida y 4.878 por 100.000 pacientes-año con anti-TNF . Conclusiones. La densidad de incidencia de tuberculosis está aumentada en nuestra población comparado con la de la población general, existiendo una mayor frecuencia de afectación extrapulmonar. La densidad de incidencia es variable en pacientes con artritis reumatoide en función de los fármacos utilizados (AU)

Lag time between onset of symptoms and access to rheumatology care and DMARD therapy in a cohort of patients with rheumatoid arthritis.

OBJECTIVE: To study demographic and clinical variables associated with a longer delay in disease modifying antirheumatic drug (DMARD) therapy initiation in a cohort of patients with rheumatoid arthritis (RA). METHODS: We studied 527 new RA patients (74.3% female, median age at symptom onset 55 yrs) in a hospital setting who fulfilled the ACR criteria for the diagnosis of RA. Demographic, clinical, laboratory, and treatment variables were collected longitudinally into a computerized research database. Risk factors for delay in use of DMARD therapy and first evaluation by a rheumatologist were analyzed using a Cox regression model. RESULTS: The median lag time between symptom onset and first rheumatologist encounter was 17 months and between onset of symptoms and first DMARD therapy 19 months. Variables associated with longer delay to DMARD therapy were the lag time between symptom onset and first rheumatologist visit (RR 0.73, 95% CI 0.71-0.76) and years of education. Variables associated with longer delay in first visit with rheumatologist were swollen/tender joint count, age at symptom onset, home support, labor force status, marital status, and years of education. CONCLUSION: Awareness of factors associated with a longer delay in access to rheumatology care and DMARD therapy may help break down barriers that prevent their early access, irrespective of patient age, socioeconomic status, initial symptoms, or need for treatment.