Use of Parenteral Methotrexate in Rheumatic Diseases: A Systematic Review. / Revisión sistemática del uso de metotrexato por vía parenteral en enfermedades reumáticas.

OBJECTIVE: To analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases. METHODS: A systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies. RESULTS: Out of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data. CONCLUSIONS: Parenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.

Assessment of SpondyloArthritis International Society (ASAS) Consensus on Spanish Nomenclature for Spondyloarthritis. / Consenso ASAS en nomenclatura en español para las espondiloartritis.

OBJECTIVE: To develop a consensus to standardize the use of Spanish terms, abbreviations and acronyms in the field of spondyloarthritis (SpA). METHODS: An international task force comprising all native Spanish-speaking Assessment of SpondyloArthritis International Society (ASAS) members, the executive committee of Grupo para el estudio de la Espondiloartritis de la Sociedad Española de Reumatología (GRESSER), two methodologists, two linguists from the Real Academia Nacional de Medicina de España (RANM) and two patients from the Spanish Coordinator of Spondylitis Associations (CEADE) was established. A literature review was performed to identify the conflicting terms/abbreviations/acronyms in SpA. This review examined written sources in Spanish including manuscripts, ICF and ICD, guidelines, recommendations and consensuses. This was followed by a nominal group meeting and a three-round Delphi. The recommendations from the RANM based on the Panhispanic dictionary were followed throughout the process. RESULTS: Consensus was reached for 46 terms, abbreviations or acronyms related to the field of SpA. A Spanish translation was accepted for 6 terms and 6 abbreviations to name or classify the disease, and for 6 terms and 4 abbreviations related to SpA. It was agreed not to translate 15 acronyms into Spanish. However, when mentioning them, it was recommended to follow this structure: type of acronym in Spanish and acronym and expanded form in English. With regard to 7 terms or abbreviations attached to acronyms, it was agreed to translate only the expanded form and a translation was also selected for each of them. CONCLUSIONS: Through this standardization, it is expected to establish a common use of the Spanish nomenclature for SpA. The implementation of this consensus across the community will be of substantial benefit, avoiding misunderstandings and time-consuming processes.

Implementation of an assessment checklist for patients with spondyloarthritis in daily practice.

OBJECTIVES: To analyse the feasibility and changes in the collection of clinical measures after the implementation in daily practice of a checklist designed for an optimal evaluation and monitoring of patients with spondyloarthritis (SpA). METHODS: An observational prospective study was performed. The feasibility of the assessment checklist (paper/on-line format) for patients with SpA was tested (time to complete the checklist, simplicity, amenity clarity, usefulness). Through a medical files review, changes in the number of the checklist variables collected were analysed previous to the implementation of the checklist and 6 months later. A descriptive and bivariate analysis was performed. RESULTS: A total 6 hospitals and 11 rheumatologists participated. The median time to checklist completion was 15 (12-20) minutes, and the mean scores for the rest of variables of the feasibility test were in general positives. A total of 83 and 68 medical files pre-implementation and post-implementation were reviewed respectively. We observed a significant increase in the collection of many of the checklist variables after the implementation. The record of BASDAI increased from 46.2% to 73.1% (p=0.001), physical activity from 48.2% to 88.2% (p<0.0001), physician global (VAS) from 28.0% to 73.5% (p<0.0001), patient global (VAS) from 48.8% to 85.3% (p<0.0001), morning stiffness from 62.8% to 84.8% (p=0.003), ASDAS from 12.2% to 32.8% (p=0.002), BASFI from 43.7% to 65.7% (p=0.008), or DAS28 from 24.7% to 46.3% (p=0.006). These changes were observed irrespectively of SpA classification. CONCLUSIONS: The implementation of an assessment checklist in daily practice is feasible and improves the assessment of SpA patients.

Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database.

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (<3 years' duration) systemic sclerosis (SSc) according to disease subsets. METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was performed. Patients fulfilling preliminary ACR 1980 classification criteria for SSc, with less than 3 years from the first non-Raynaud's symptom at first entry, were selected. A group of patients with less than 3 years from the first SSc symptom, including Raynaud's phenomenon, was also analysed. SSc related variables, including antibodies, SSc subsets, disease activity and organ involvement were included. Descriptive and bivariate analyses were performed. RESULTS: A total of 1,027 patients were included, 90% Caucasian, 80% women, and 40% with diffuse cutaneous disease. In early stages of SSc, men showed more frequently than women active disease, diffuse cutaneous subset, anti-Scl-70 antibodies, elevated acute phase reactants, muscular and pulmonary involvement. Differences between men and women were confirmed in the limited, but not in the diffuse SSc subset. The results were similar when 650 patients with less than three years from the first SSc symptom, including Raynaud's phenomenon, were analysed. CONCLUSIONS: In early stages of SSc, men present signs and symptoms of more severe disease. In the limited disease subset, men might appear with clinical features and organ involvement similar to those of the diffuse subgroup. In clinical practice, the identification of such differences might help to select the appropriate management for each particular patient.

Expert recommendations on the psychological needs of patients with rheumatoid arthritis.

OBJECTIVE: To establish feasible and practical recommendations for the management of the psychological needs of patients with rheumatoid arthritis (RA) from the moment of diagnosis through the course of the disease. METHODS: A nominal group meeting was held with an RA expert team including rheumatologists and psychologists, at which a guided discussion addressed the most important psychological and emotional needs in RA. Based on the comments collected, and a literature review, a matrix document of recommendations for telematics discussion was prepared, as well as a Delphi survey to test agreement with these recommendations. Agreement was defined if at least 80% of participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grading of recommendations was established following the Oxford criteria, and the degree of agreement through the Delphi. RESULTS: Thirteen recommendations were established, addressing several key processes: (1) identification of psychological problems and needs in patients with RA, and a guideline for their management in daily practice; (2) communication with patients; (3) referral criteria to mental health professionals. CONCLUSIONS: These recommendations are intended to help health care professionals openly address the psychological aspects of patients in daily practice to follow and treat them properly.

Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis: a systematic literature review.

OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.

OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Impact of the use of musculoskeletal ultrasound by rheumatologists in patients with shoulder and hand complaints compared with traditional clinical care.

OBJECTIVES: To compare the routine use of musculoskeletal ultrasonography (MSUS) with traditional clinical care in daily practice at shoulder and hand level. METHODS: An observational study was performed in four rheumatology departments. Within each department, 2 rheumatologists were selected; one rheumatologist used MSUS, and the other followed traditional rheumatology care. Consecutive patients with nontraumatic pain, hand numbness or disability, or pain and/or limitations in the shoulder were selected. We collected information regarding the clinical and MSUS diagnoses, changes in diagnosis and treatment following MSUS, local injections, the rheumatologist's satisfaction and the use of health care resources. A descriptive analysis was performed. RESULTS: A total of 168 patients were analysed, with 104 and 64 patients in the MSUS and traditional care groups, respectively. MSUS led to a diagnosis and therapeutic change in 53 (52%) and 55 patients (54%), respectively. The rate of local injection was 47% in the MSUS group (73% unexpected, 61% performed using US) compared with 21% in the traditional group (p=0.001). According to the rheumatologists, MSUS was useful in 72 cases (71%) and extremely useful in 20 cases (20%), and the rheumatologists reported a higher satisfaction with their patient evaluations (p<0.001). The MSUS group required fewer additional tests (38% vs. 81%, respectively, p<0.001), fewer medical visits (46% vs. 84%, p<0.001), and lower direct costs (11 vs. 30 euros, p<0.001) than the traditional care group. CONCLUSIONS: Compared with traditional care, the routine use of MSUS in rheumatology practice at hand and shoulder level can lead to important improvements in care, thereby reducing the number of additional tests and medical visits.

[Consensus statement of the Spanish Society of Rheumatology on risk management of biologic therapy in rheumatic patients]. / Consenso SER sobre la gestión de riesgo del tratamiento con terapias biológicas en pacientes con enfermedades reumáticas.

OBJECTIVE: Due to the increasing use of biologic therapy in rheumatic diseases and the importance of its risk management, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and those involved in the treatment of patients who are using, or about to use biologic therapy irrespectively of the rheumatic disease. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Evidence from previous consensus and clinical guidelines was used. RESULTS: We have produced recommendations on risk management of biologic therapy in rheumatic patients. These recommendations include indication risk management, risk management before the use of biologic therapy, risk management during follow-up, attitude to adverse events, and attitude to special situations. CONCLUSIONS: We present the SER recommendations related to biologic therapy risk management.

Effectiveness of an early cognitive-behavioral treatment in patients with work disability due to musculoskeletal disorders.

OBJECTIVE: To evaluate whether an early cognitive-behavioral treatment complementary to a rheumatologic care program, for patients with recent-onset temporary work disability caused by musculoskeletal disorders (MSDs) is effective. METHODS: Patients with an MSD-related temporary work disability episode from 3-8 weeks' duration who were in a rheumatologic care program were randomized into a control group (rheumatologic care program) or an intervention group (rheumatologic care program plus cognitive-behavioral treatment). Enrollment lasted 24 months and followup lasted 6-24 months. Efficacy variables included duration of temporary work disability episodes, total number of work days saved, relative efficacy, and relative rate to return to work. An economic evaluation was also performed. RESULTS: One hundred eighty-one patients were included (66 control and 115 intervention patients), generating 222 episodes of MSD-related temporary work disability. Episodes tended to be shorter in the intervention group than in the control group (mean 98 versus 127 days; P = 0.053), with a relative efficacy of 22.9%. There were no differences in duration of the first episode between groups (mean 105 versus 110 days; P = 0.79), but relapse episodes were significantly shorter in the intervention group (mean 63 days versus 197 days; P = 0.0002). Costs were also lower in the intervention group. To save 1 day of temporary work disability, $13.50 had to be invested in the program. Each dollar invested generated a benefit of $4.08. The program had a net benefit of $172,607. CONCLUSION: Early cognitive-behavioral treatment complementary to a rheumatologic care program is cost-effective, adds >20% efficacy to the rheumatologic care program, and reduces the duration of relapses.

Economic burden of knee and hip osteoarthritis in Spain.

OBJECTIVE: To estimate the direct and indirect osteoarthritis (OA)-attributable costs and predictors of costs of knee and hip OA in Spain. METHODS: This study included consecutive patients age > or = 50 years with symptomatic and radiologic knee and/or hip OA who were seen at primary care centers in all provinces of Spain. Information on demographics, health status (Short Form 12 Health Survey), comorbidities (Charlson Index), clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and radiologic OA severity (Kellgren/Lawrence [K/L] scale), data related to OA health resources utilization (medical and nonmedical), and subjects' and caregivers' expenses and time lost in the previous 6 months were collected in 2 separate, structured, and detailed interviews. Costs in euros were assigned using market prices and official sources if available, and were annualized (to 2007). The predictors of costs were assessed in multivariate regression models. Costs were log-transformed before being modeled. RESULTS: A total of 1,071 subjects were analyzed (74% women, mean +/- SD age 71 +/- 9 years). Average total annual costs were euro1,502 per patient. Direct costs accounted for 86% of the total cost. We estimated a national cost of euro4,738 million, representing 0.5% of the gross national product. Higher total costs were associated with comorbidity (Charlson Index odds ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03-1.58), poorer health status (P < 0.050), worse WOMAC scores (OR 1.05, 95% CI 1.03-1.08), and grade 4 K/L scores (OR 1.76, 95% CI 1.15-2.69). CONCLUSION: The economic burden of knee and hip OA is substantial. Costs increased with comorbidity, poorer health status, and clinical and radiologic OA severity.

Burden of disease across chronic diseases: a health survey that measured prevalence, function, and quality of life.

OBJECTIVE: To assess health related quality of life (HRQOL) and functional ability across groups of chronic diseases in Spain. METHODS: A national health survey was conducted during 1999-2000. Participants were randomly selected from city censuses among persons aged over 20 years. All 2192 participants (response rate 73%) completed generic instruments measuring functional ability in activities of daily living [Health Assessment Questionnaire (HAQ)] and HRQOL [Short-Form 12 (SF-12)]. Chronic diseases were defined by self-report and elicited from 2 specific questions: "Have you ever been told you have a chronic disease by a physician?" and "Are you taking any chronic medication?". Only diagnoses present for > or = 3 months were included as chronic. We estimated mean HAQ and SF-12 scores for the different groups of chronic diseases. We then adjusted the scores for covariates and compared them between diseases by multiple linear regressions. RESULTS: Over half the population had at least one chronic disease [n = 1276 (58.2%)], and 22.6% had any rheumatic disease. Rheumatic diseases have an adverse effect on daily functioning [HAQ beta-coefficient 0.11 (95% CI 0.06-0.15)] and HRQOL [SF-12 physical beta-coefficient -5.78 (95% CI -6.27 to -4.28); SF-12 mental beta-coefficient -2.61 (95% CI -3.79 to -1.41)]. Thus, the influence of the rheumatic diseases is greater when their prevalence is taken into account. CONCLUSION: When the definition of burden of disease includes a measure of function and HRQOL that is weighted by disease prevalence, rheumatic diseases as a group can be ranked alongside neurological, cardiac, or pulmonary conditions as a major disease.