Local adaptation of recommendation-based materials for shared decision-making and management of comorbidity in rheumatoid arthritis.

OBJECTIVES: To describe local adaptations of materials derived from evidence-based recommendations in a training programme in rheumatoid arthritis (RA). METHODS: The eRA (evolving the management of rheumatoid arthritis) programme generated shared decision-making practises and a checklist for managing comorbidity in RA, among others, at the international level. Unmet needs in RA management were first identified and prioritised. Then educational materials were designed and developed to address these gaps. These materials were evaluated in detailed and discussed in small regional groups by practicing rheumatologists. Voting, open discussions and recommendations were extracted from the meetings. RESULTS: Thirty-five Spanish rheumatologists discussed a comorbidity checklist and a shared decision-making tool. The results of the local meetings were synthesised as (1) a judicious commitment to check agreed comorbidities, and (2) a list of barriers and facilitators for the implementation of shared decision making in the local settings. With regards to ways to implement the agreed list and periodicity, two issues stand-out: (1) patient education and (2) the need of easy access to information and the use of local organisational systems in place. With respect to shared decision-making, issues raised included messages for self-awareness, challenges, and practical facilitators. CONCLUSIONS: Discussion, adaptation, and planning are needed before implementing any evidence-based recommendation and materials if we want to achieve a successful implementation. Further studies should demonstrate whether this initiative was successful in achieving the goals of improved patient care. Our experience could be used as a guidance or example for implementation elsewhere.

Impaired microRNA processing in neutrophils from rheumatoid arthritis patients confers their pathogenic profile. Modulation by biological therapies.

The aim of this study was to investigate the microRNA (miRNA) expression pattern in neutrophils from rheumatoid arthritis (RA) patients and its contribution to their pathogenic profile and to analyze the effect of specific autoantibodies or inflammatory components in the regulation of miRNA in RA neutrophils and its modulation by biological therapies. Neutrophils were isolated from paired peripheral blood (PB) and synovial fluid samples of 40 patients with RA and from PB of 40 healthy donors. A miRNA array was performed using nCounter technology. Neutrophils from healthy donors were treated in vitrowith antibodies to citrullinated protein antigens isolated from RA patients and tumor necrosis factor-a (TNF-a) or interleukin-6. A number of cytokines and chemokines were analyzed. In vitro treatments of RA-neutrophils with tocilizumab or infliximab were carried out. Transfections with pre-miRNA and DICER downregulation experiments were further performed. RA-neutrophils showed a global downregulation of miRNA and genes involved in their biogenesis, alongside with an upregulation of various potential mRNA targets related to migration and inflammation. Decreased levels of miRNA and DICER correlated with autoimmunity, inflammation and disease activity. Citrullinated protein antigens and TNF-a decreased the expression of numerous miRNA and their biogenesis-related genes, increasing their potential mRNA targets. Infliximab reversed those effects. Transfections with pre-miRNA-223, -126 and -148a specifically modulated genes regulating inflammation, survival and migration whereas DICER depletion influenced the inflammatory profile of neutrophils. Taken together RA-neutrophils exhibited a global low abundance of miRNA induced by autoantibodies and inflammatory markers, which potentially contributed to their pathogenic activation. miRNA biogenesis was significantly impaired in RAneutrophils and further associated with a greater downregulation of miRNA mainly related to migration and inflammation in synovial fluid neutrophils. Finally, anti-TNF-a and anti-interleukin-6 receptor treatments can modulate miRNA levels in the neutrophils, minimizing their inflammatory profile.

Recomendaciones sobre el uso de metrotexato parenteral en enfermedades reumáticas / Recommendations for the use of parenteral methotrexate in rheumatic diseases

Objetivos. Desarrollar recomendaciones sobre el uso de metrotexato (MTX) parenteral en pacientes con enfermedades reumáticas, fundamentalmente en la artritis reumatoide, basadas en la mejor evidencia y experiencia. Métodos. Se seleccionó un grupo de 21 expertos reumatólogos en el manejo de MTX. El coordinador generó 13 preguntas sobre el uso de MTX parenteral (perfiles de indicación, eficacia, seguridad, costo-eficacia y biodisponibilidad) para ser contestadas mediante una revisión sistemática de la literatura. Con base en las preguntas se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda (en Medline, EMBASE y la Cochrane Library). Tres revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente se evaluaron abstracts de congresos de la European League Against Rheumatism (EULAR) y del American College of Rheumatology (ACR). Con toda esta evidencia el coordinador generó 13 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión del grupo nominal con los expertos. Para cada recomendación se estableció el nivel de evidencia y grado de recomendación, y el grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestaron sí a la recomendación (sí o no). Resultados. La mayoría de la evidencia proviene de la artritis reumatoide. De las 13 recomendaciones preliminares se aceptaron 11 recomendaciones sobre el uso de MTX parenteral en reumatología. Dos no se llegaron a votar y se decidió no incluirlas, pero se comentan en el texto final. Conclusiones. Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el uso de MTX parenteral

Objective. To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. Methods. A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results. Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. Conclusions. The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX

Recommendations for the use of parenteral methotrexate in rheumatic diseases. / Recomendaciones sobre el uso de metrotexato parenteral en enfermedades reumáticas.

OBJECTIVE: To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. METHODS: A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). RESULTS: Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. CONCLUSIONS: The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX.

Recomendaciones para el uso de metotrexato en artritis reumatoide establecida: monoterapia y combinación con otros fármacos modificadores de la enfermedad sintéticos o biológicos / Recommendations for the use of methotrexate in established rheumatoid arthritis: monotherapy and combination with other synthetic or biological DMARDs

El metotrexato, utilizado a dosis bajas semanales, es actualmente el tratamiento de referencia en la artritis reumatoide. No se conoce con exactitud el mecanismo de acción en esta enfermedad, pero se han descrito diversas acciones antiproliferativas, antiinflamatorias e inmunorreguladoras que pueden contribuir a su efecto terapéutico. Diversos ensayos clínicos demostraron en la década de los ochenta del siglo pasado su eficacia clínica, así como su efecto enlentecedor del daño anatómico. En los últimos años se ha visto además que llegar a dosis más altas de las inicialmente utilizadas, entre 25 y 30 mg/semanales, puede maximizar sus efectos. En pacientes resistentes, el metotrexato también puede ser útil en terapia combinada con otros fármacos modificadores de la enfermedad, sintéticos o biológicos. Habitualmente, el metotrexato es bien tolerado, pero puede tener efectos adversos a diversos niveles (hematológico, digestivo, hepático, neurológico o pulmonar), alguno de los cuales pueden ser graves, por lo que requiere una cuidadosa monitorización clínica y analítica (AU)

The aim of this document is to describe the optimal use of: a) methotrexate (MTX) monotherapy in established RA in readministration after a previous effective cycle, and b) MTX combination with synthetic and biological DMARD. Clinical questions were proposed and a systematic literature search was conducted. Recommendations were developed and then discussed and validated in a working session with fifteen experts. After an effective cycle, MTX will be restarted with the same dose and route of administration than previously, following an intensive strategy if the dose were insufficient or the patient had poor prognostic factors. When sustained remission, MTX may be reduced gradually, with a close monitoring of the patient. Before starting a combination therapy with other synthetic or biologic DMARD, full doses of MTX should be reached and the use of the parenteral route evaluated. In established RA, when starting the combination of MTX with a biological DMARD, the same dose and route of administration of MTX than previously used should be maintained. In patients in remission for at least 6 months and in combination therapy with a biological, it is recommended to reduce the dose of the biological agent or increase its administration period before reducing the dose of MTX, unless side effects due to MTX. This document pretends to solve some frequent clinical questions on the use of MTX in monotherapy and/or in combination therapy with other synthetic or biological DMAR (AU)

Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study.

OBJECTIVE: The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients. METHODS: This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression. RESULTS: A total of 23 single nucleotide polymorphisms and the time of primary KOA diagnosis were significantly associated with KOA severe progression in the exploratory cohort (n = 220; P < 0.05). The predictive accuracy of the clinical variables was limited: area under the curve (AUC) = 0.66. When genetic variables were added to the clinical model (full model), the prediction of KOA progression was significantly improved (AUC = 0.82). Combining only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also obtained (AUC = 0.78). The predictive ability for KOA progression of the full model was confirmed on the replication cohort (two-sample Z-test; n = 62; P = 0.190). CONCLUSION: An accurate prognostic tool to predict primary KOA progression has been developed based on genetic and clinical information from OA patients.

Assessment of the efficacy of joint lavage versus joint lavage plus corticoids in patients with osteoarthritis of the knee.

PURPOSE: Joint lavage (JL), involves the passage of cold sterile 0.9% saline through the knee joint in order to have the fluid reach the inside of the joint capsule. This technique was evaluated as a local treatment for osteoarthritis (OA) of the knee alone (JL) and in combination with intra-articular infiltration with glucocorticoids (JLC). PATIENTS AND METHODS: An overall 299 knees belonging to 205 patients (22% males, 78% females) with a mean age of 67 +/- 8 years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were randomised in the ratio of 1:4 into two therapeutic groups, namely: JL (n = 62) and JLC (n = 237). All patients received joint lavage on day 0; in those of the JLC group, joint lavage was followed by infiltration of 40 mg of triamcinolone acetonide. The efficacy of both treatments was assessed by recording the corresponding values for the following variables: pain strength as measured by a visual analogy scale (VAS), effusion, crepitation, restricted motion, of osteoarthritis of the knee. spontaneous pain, pain on pressure, pain on passive motion and pain on active motion; all of these were recorded at the onset of the study, and after 1 and 3 months. RESULTS: There were no significant differences in the values of the variables at the different followup times. Also, pain severity was similar in both treatment groups. Thus, VAS for pain was 7.3 +/- 0.3 for the JL group and 7.1 +/- 0.2 for the JLC group at the onset, and decreased to 3.0 +/- 0.3 in the former and 2.8 +/- 0.2 in the latter after 1 month; the decrease was statistically significant in both cases. After 3 months, the JL and JLC groups had a VAS of 3.5 +/- 0.3 and 3.8 +/- 0.2, respectively. CONCLUSIONS: The results of this work suggest the absence of significant differences between the two treatments, such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management