Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting.

OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting. MATERIALS AND METHODS: Non-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed. RESULTS: Of the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (n=46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%). CONCLUSIONS: In a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.

Body Mass Index and Disease Activity in Chronic Inflammatory Rheumatic Diseases: Results of the Cardiovascular in Rheumatology (Carma) Project.

OBJECTIVE: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. METHODS: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. RESULTS: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (ß = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (ß = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (ß = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. CONCLUSIONS: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients.

Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe?

BACKGROUND: The recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2. OBJECTIVES: To estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain. METHODS: We performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection. RESULTS: There were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative. CONCLUSIONS: Overall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.

Apremilast in refractory orogenital ulcers and other manifestations of Behçet's disease. A national multicentre study of 51 cases in clinical practice.

OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

"There is something you must see": breaking down the remission concept in rheumatoid arthritis from a rheumatologist's perspective.

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.

Evolución a largo plazo de la calidad de vida en pacientes con artritis reumatoide tratados con terapias biológicas / Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies

Objetivo: Analizar la evolución a largo plazo de la calidad de vida relacionada con la salud (CVRS) en pacientes con artritis reumatoide (AR) tratados con terapias biológicas. Método: Estudio observacional prospectivo realizado entre octubre de 2006 y mayo de 2011. Se seleccionó a pacientes mayores de edad, diagnosticados de AR, tratados durante al menos un año con anti-TNF (infliximab o etanercept) y que no hubieran recibido otros tratamientos biológicos previos. Completaron el estudio 41 pacientes, cumplimentando el cuestionario específico validado QOL-AR en 3ocasiones: E1 (entre septiembre de 2006 y febrero de 2007), E2 (entre abril de 2008 y enero de 2009) y E3 (entre julio de 2010 y mayo de 2011). Los datos se analizaron con Epi-Info versión 3.3-2004 para Windows (R) y Excel 2007; la comparación de las medias con la prueba t de Student y la relación entre valores de un mismo paciente, mediante regresión lineal. Resultados: Resultados globales: tendencia descendente no estadísticamente significativa: 7,09±1,15 en E1; 6,90±1,60 en E2 y 6,52±1,59 en E3. Los ítems con mayor puntuación fueron los relacionados con aspectos psicosociales (ayuda familiar, interacción con familia y amigos). La dimensión física fue la peor valorada (habilidad física, dolor artrítico, artritis). Entre E2 y E3 aumentó significativamente la valoración de la ayuda familiar (p=0,0008) y disminuyeron significativamente tensión nerviosa (p=0,0119) y estado de ánimo (p=0,0451). Conclusiones: La CVRS de los pacientes es buena y se ha mantenido prácticamente invariable tras unos 6años de estudio. Es probable que parte de la estabilidad en la CVRS sea atribuible al tratamiento

Objective: To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Method: Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows(R) and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Results: Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. Conclusions: In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.

Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies. / Evolución a largo plazo de la calidad de vida en pacientes con artritis reumatoide tratados con terapias biológicas.

OBJECTIVE: To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. METHOD: Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. RESULTS: Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. CONCLUSIONS: In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment.

Exploring the remission concept in rheumatoid arthritis with patients and rheumatologists: time for a new approach?

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to compare remission definitions and related concepts between rheumatologists and patients with the purpose of identifying similarities and disparities to comprehend the different perspectives of the disease. METHODS: This was a qualitative study of discourse and content analysis through focus groups, conducted from February to March 2016. Four focus groups were set up, each one with different interests: rheumatologists involved in basic research (BR), rheumatologists with high specialisation in imaging techniques (IR), clinical rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a remission definition in RA; differences exist between-groups, rheumatologists and patients value remission differently, and there are discrepancies within the group of rheumatologists. Rheumatologists highlight quantifiable objective parameters, in contrast, patients did not consider objective measures as the best instruments, and they prefer subjective measures of remission. The data confirmed the existence of two sources of knowledge of the disease, technical (physicians) and experiential (patients). These sources of knowledge should concur in order to establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack of consensus between key groups implicated in defining remission and remission criteria suggests a new strategy for its operational definition. Our group proposes that subjects with a balance between experiential and technical knowledge, should be the ones in charge of this assignment.

Estándares de calidad asistencial para las consultas externas de reumatología. El proyecto EXTRELLA / Quality standards for rheumatology outpatient clinic. The EXTRELLA project

Introducción. En los últimos años, el peso específico de las consultas externas ha aumentado considerablemente. En la actualidad, la mayor parte de la atención reumatológica se lleva a cabo en esta área del hospital. Sin embargo, apenas existe documentación respecto a estándares de calidad asistencial. Objetivo. Desarrollar, mediante consenso, estándares de calidad asistencial específicos para las consultas externas de reumatología. Método. El proyecto se llevó a cabo mediante metodología Delphi a 2 rondas. Se contó con la participación de un comité científico (13 reumatólogos), 5 grupos nominales (45 reumatólogos y 12 enfermeras especializadas) y un grupo de discusión formado por 9 pacientes. Se generaron de forma sucesiva diversos borradores hasta obtener un documento final que incluyó los estándares que recibieron una puntuación igual o superior a 7 en al menos el 70% de los participantes. Resultados. El documento consta de 148 estándares distribuidos en 9 áreas temáticas: a) estructura (22); b) actividad clínica y relación con los pacientes (34); c) planificación (7); d) niveles de prioridad (5); e) relación con atención primaria, con el servicio de urgencias y con otros servicios del hospital (20); f) proceso (26); g) enfermería (13); h) docencia e investigación (13), e i) cómputo de actividad (8). Conclusión. Se han consensuado unos estándares de calidad asistencial que pueden ser útiles para organizar la actividad en las consultas externas de los servicios de reumatología y servir como marco de referencia a la hora de elevar propuestas de mejora a la gerencia del hospital o a otros estamentos de la administración (AU)

Introduction. In recent years, outpatient clinics have undergone extensive development. At present, patients with rheumatic diseases are mainly assisted in this area. However, the quality standards of care are poorly documented. Objective. To develop specific quality criteria and standards for an outpatient rheumatology clinic. Method. The project was based on the two-round Delphi method. The following groups of participants took part: scientific committee (13 rheumatologists), five nominal groups (45 rheumatologists and 12 nurses) and a group of discussion formed by 9 patients. Different drafts were consecutively generated until a final document was obtained that included the standards that received a punctuation equal or over 7 in at least 70% of the participants. Results. 148 standards were developed, grouped into the following 9 dimensions: a) structure (22), b) clinical activity and relationship with the patients (34), c) planning (7), d) levels of priority (5), e) relations with primary care physicians, with Emergency Department and with other clinical departments, f) process (26), g) nursing (13), h) teaching and research (13) and i) activity measures (8). Conclusion. This study established specific quality standards for rheumatology outpatient clinic. It can be a useful tool for organising this area in the Rheumatology Department and as a reference when proposing improvement measures to health administrators (AU)

Quality standards for rheumatology outpatient clinic. The EXTRELLA project. / Estándares de calidad asistencial para las consultas externas de reumatología. El proyecto EXTRELLA.

INTRODUCTION: In recent years, outpatient clinics have undergone extensive development. At present, patients with rheumatic diseases are mainly assisted in this area. However, the quality standards of care are poorly documented. OBJECTIVE: To develop specific quality criteria and standards for an outpatient rheumatology clinic. METHOD: The project was based on the two-round Delphi method. The following groups of participants took part: scientific committee (13 rheumatologists), five nominal groups (45 rheumatologists and 12 nurses) and a group of discussion formed by 9 patients. Different drafts were consecutively generated until a final document was obtained that included the standards that received a punctuation equal or over 7 in at least 70% of the participants. RESULTS: 148 standards were developed, grouped into the following 9 dimensions: a) structure (22), b) clinical activity and relationship with the patients (34), c) planning (7), d) levels of priority (5), e) relations with primary care physicians, with Emergency Department and with other clinical departments, f) process (26), g) nursing (13), h) teaching and research (13) and i) activity measures (8). CONCLUSION: This study established specific quality standards for rheumatology outpatient clinic. It can be a useful tool for organising this area in the Rheumatology Department and as a reference when proposing improvement measures to health administrators.

Recomendaciones para el uso del metotrexato en artritis reumatoide: incremento y reducción de dosis y vías de administración / Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes

Objetivos. Describir la estrategia terapéutica óptima de uso de metotrexato en AR sobre dosis inicial, vía de administración, incremento y disminución de dosis, seguimiento del paciente y uso de ácido fólico/folínico. Material y método. Once expertos plantearon los interrogantes clínicos a resolver. Se realizó una búsqueda bibliográfica sistemática. Los contenidos fueron seleccionados en una sesión de trabajo y el nivel de acuerdo se estableció posteriormente en una ronda de consenso vía correo. Resultados. La dosis de inicio de metotrexato no debe ser < 10 mg/semana, preferentemente por vía oral, considerando la vía parenteral como alternativa según el cumplimento, ineficacia o efectos secundarios gastrointestinales, polimedicación, obesidad (si requiere dosis > 20 mg/semana), preferencias del paciente, enfermedad muy activa o para evitar errores de medicación. Se cambiará a la vía parenteral cuando haya ineficacia, toxicidad gastrointestinal, incumplimiento o por coste-efectividad antes de pasar a fármacos más caros; y a la inversa, según preferencias del paciente, intolerancia a inyectables, reducción de dosis < 7,5 mg/semana, ineficacia, bajo cumplimiento o efectos adversos gastrointestinales. Se realizará escalada rápida de dosis si la respuesta es inadecuada hasta los 15-20 o, incluso, 25 mg/semana en unas 8 semanas, con incrementos de 2,5-5 mg. La reducción se realizará según la dosis a la que estuviera el paciente, con disminuciones de 2,5-5 mg cada 3-6 meses. El seguimiento del paciente deberá realizarse cada 1-1,5 meses hasta la estabilidad y luego cada 1-3 meses. Conclusiones. Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones en la AR tratada con metotrexato (AU)

Objectives, To describe the optimal therapeutic strategy for use of methotrexate in RA patients over the initial dose, route of administration, dose increase and decrease, patient monitoring, and use of folic/folinic acid. Materials and methods. Eleven clinical experts proposed some questions to be solved. A systematic literature search was conducted. The contents were selected in a work session and subsequently validated via email to establish the level of agreement. Results. The initial dose of methotrexate should not be <10 mg/week, preferably orally, but the parenteral route is considered as an alternative due to compliance, non-effectiveness of treatment or gastrointestinal side effects, polypharmacy, obesity (if required doses are >20 mg/week), patient preference, very active disease or to avoid administration errors. Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs. On the contrary, due to patient preferences, intolerance to injections, dose reduction <7.5 mg/week, non-effectiveness of the route, poor compliance or gastrointestinal side effects. There should be a rapid dose escalation if inadequate responses occur up to 15–20 or even 25 mg/week in about 8 weeks, with increments of 2.5–5 mg. The reduction will be carried out according to the dose the patient had, with decreases of 2.5–5 mg every 3–6 months. Patient monitoring should be performed every 1–1.5 months until stability is reached and then for every 1–3 months. Conclusions. This document pretends to solve some common clinical questions and facilitate decision-making in RA patients treated with methotrexate (AU)

Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes.

OBJECTIVES: To describe the optimal therapeutic strategy for use of methotrexate in RA patients over the initial dose, route of administration, dose increase and decrease, patient monitoring, and use of folic/folinic acid. MATERIAL AND METHOD: Eleven clinical experts proposed some questions to be solved. A systematic literature search was conducted. The contents were selected in a work session and subsequently validated via email to establish the level of agreement. RESULTS: The initial dose of methotrexate should not be <10mg/week, preferably orally, but considering the parenteral route as an alternative due to compliance, non effectiveness of treatment or gastrointestinal side effects, polypharmacy, obesity (if required doses are >20mg/week), patient preference, very active disease or to avoid administration errors. Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs. On the contrary, due to patient preferences, intolerance to injections, dose reduction <7.5mg/week, non effectiveness of the route, poor compliance or gastrointestinal side effects. There should be a rapid dose escalation if inadequate responses occurr up to 15-20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg. The reduction will be carried out according to the dose the patient had, with decreases of 2.5-5mg every 3-6 months. Patient monitoring should be performed every 1-1.5 months until stability and then every 1-3 months. CONCLUSIONS: This document pretends to solve some common clinical questions and facilitate decision-making in RA patients treated with methotrexate.