Sagrario Bustabad

Power Doppler Ultrasonography Assessment of Entheses in Spondyloarthropathies: Response to Therapy of Entheseal Abnormalities

Objective. To investigate the response to therapy of entheseal abnormalities assessed with power Doppler (PD) ultrasound (US) in spondyloarthropathies (SpA). Methods. A total of 327 patients with active SpA who were starting anti-tumor necrosis factor (TNF) therapy were prospectively recruited at 35 Spanish centers. A PDUS examination of 14 peripheral entheses was performed by the same investigator in each center at baseline and at 6 months. The following elementary lesions were assessed at each enthesis (presence/absence): morphologic abnormalities (hypoechogenicity and/or thickening), entheseal calcific deposits, cortical abnormalities (bone erosion and/or proliferation), adjacent bursitis and intraenthesis and perienthesis (tendon body and/or bursa) PD signal. Response to therapy of each elementary lesion was assessed by calculating change in the cumulative presence from baseline to 6 months. Intraobserver reliability of PDUS was evaluated by blindly assessing the stored baseline images 3 months after the real-time examination. Results. Complete data were obtained on 197 patients who received anti-TNF therapy for 6 months. In 91.4% of the patients there were gray-scale or PD elementary lesions at baseline and at 6 months. Cumulative entheseal morphologic abnormalities, intraenthesis PD, perienthesis PD, and bursitis showed a significant decrease from baseline to 6 months (p < 0.05). There was high intraobserver reliability for all elementary lesions (interclass correlation coefficient > 0.90, p < 0.0005). Conclusion. Entheseal morphologic abnormalities, PD signal, and bursitis were US abnormalities that were responsive to anti-TNF therapy in SpA. PDUS can be a reproducible method for multicenter monitoring of therapeutic response in enthesitis of SpA.

Differential Antigen-presenting B Cell Phenotypes from Synovial Microenvironment of Patients with Rheumatoid and Psoriatic Arthritis

Objective. To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Methods. The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR. Results. Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138−) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA. Conclusion. Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.

Tocilizumab en pacientes con artritis reumatoide activa y respuesta inadecuada a fármacos antirreumáticos modificadores de la enfermedad o antagonistas del factor de necrosis tumoral: subanálisis de los datos españoles de un estudio abierto cercano a la práctica clínica habitual

OBJECTIVES To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. MATERIAL AND METHODS Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. RESULTS The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. CONCLUSIONS Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis.

Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.

Objetivos y metodología de la fase iii de BIOBADASER

OBJECTIVE Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). METHODOLOGY Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. RESULTS During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. CONCLUSIONS BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.

Estudio EPISER 2016. El porqué de un nuevo estudio epidemiológico

Epidemiological information is fundamental in that it enables us to measure the importance of diseases in terms of social and public health and contributes to proper health care planning. Epidemiological studies are descriptive observational reports that provide knowledge on the disease burden in a general population, and one of their purposes is to describe the prevalence of diseases. These studies enable us to compare populations, or different moments in a given population, and thus to generate hypotheses about the possible causes of differences in the prevalences of the diseases being considered. Epidemiological analysis is of great interest not only for health care professionals, but for health care managers and financial backers. These investigations help the latter, whether they work in public administrations or in insurance companies, to estimate the expenses involved in the inclusion of novel drugs into the market. Epidemiological studies of the musculoskeletal diseases, most of which are chronic and have a marked socioeconomic impact. Although they are associated with a high consumption of health care resources, there are few reports on them in Spain.1–3 The EPISER 2000 study,4–6 which examined the prevalence of rheumatic diseases in the Spanish adult population over 20 years of age, is 1 of the strategic projects of the Spanish Society of Rheumatology (Sociedad Española de Reumatología [SER]). The EPISER 2000 initiative was the first population-based study, a representative of the adult population in Spain, in which the authors estimated the prevalence and impact of 6 rheumatic disorders: rheumatoid arthritis, systemic lupus erythematosus, low back pain, hand and knee osteoarthritis, fibromyalgia and osteoporosis. The findings to date are considered representative of the Spanish population and are being utilized by the Spanish Ministry of Health to calculate the reimbursement corresponding to the new medications that are indicated in some of the rheumatic diseases studied. During 2016, the SER, for different reasons, has established among its strategic objectives the conduction of a new epidemiological study of rheumatic diseases in adults, EPISER

Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil

OBJECTIVES To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). MATERIAL AND METHOD A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. RESULTS MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. CONCLUSIONS This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

Satisfacción, cumplimento de expectativas y adherencia al fármaco biológico subcutáneo en pacientes con artritis reumatoide. Estudio ARCO

OBJECTIVES In the ARCO study, adherence to subcutaneous biological agents by patients with rheumatoid arthritis improved with monthly administration. We assess whether adherence can be related to fulfillment of expectations and satisfaction with treatment. PATIENTS AND METHODS Adherence was assessed by calculating the Medication Possession Ratio, and satisfaction and fulfillment of expectations using the «EXPRESAR» group questionnaire. RESULTS In 346 patients, those who were satisfied/very satisfied with efficacy and tolerability were ≥80% and 64.4%, with no differences between weekly, biweekly or monthly administration regimens. Regarding the fulfillment of expectations, 59.9% considered the effect of the treatment greater than expected and 52.6% reported lower/much lower than expected discomfort; the latter percentage was higher in patients with monthly administration (P=.049). The percentages for nonadherence were 15.6% (discomfort greater than expected), 18.5% (expected discomfort) and 11.1% (lower than expected or no discomfort) (P=.189). CONCLUSIONS Satisfaction and fulfillment of expectations were high. Fulfillment of expectations of tolerability was better with monthly administration, which could contribute to better adherence.

Recomendaciones de experto sobre el bloqueo de la interleucina 6 en pacientes con artritis reumatoide

OBJECTIVE To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience. METHODS A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre 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 The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management. CONCLUSIONS The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.

Recomendaciones sobre el uso de metotrexato en pacientes con artritis psoriásica

OBJECTIVES To develop recommendations for the management of methotrexate (MTX) in psoriatic arthritis (PsA), based on best evidence and experience. METHODS A group of 12 experts on MTX use was selected. The coordinators formulated 14 questions about the use of MTX in PsA patients (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 (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed 12 preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre 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 A total of 12 preliminary recommendations on the use of MTX were proposed, 9 of which were accepted. One was included in a different recommendation and another 2 were not voted on and were thereafter clarified in the main text. CONCLUSIONS These recommendations aim to answer frequent questions and help in decision making strategies when treating PsA patients with MTX.