Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Silicone ring tourniquet versus pneumatic cuff tourniquet in total knee arthroplasty surgery: A randomised comparative study.

INTRODUCTION: The aim of the present study was to compare a silicone ring tourniquet (SRT) and a classic pneumatic cuff tourniquet (PT) in patients undergoing total knee replacement. We have compared the impact on the glycolytic activity caused by the ischaemia applied to the limb during the surgery. MATERIAL AND METHODS: 140 patients that underwent total knee arthroplasty (TKA) were randomised in two groups. Serum lactate determination was made by reactive strips of enzymatic-amperometric detection, 5 min before tourniquet application and 5 min after tourniquet removal. RESULTS: The mean tourniquet time was similar for both groups (p 0.13). Postoperative serum lactate levels were higher with statistical significance than the preoperative levels and with a positive Pearson´s correlation in the overall cases. The postoperative serum lactate levels where higher in the PT group (4.097 ±â€¯2.248 mmol/L) than the SRT group (3.499 ±â€¯1.566 mmol/L). There was no significant difference (p 0.07) to be able to affirm that there was a difference of the anaerobic metabolism according to the tourniquet system used. DISCUSSION: Ischaemia applied to the lower extremity during knee replacement surgery can produce tissue injury. Serum lactate determination allows comparison of the ischaemic changes during TKA surgery caused by two different tourniquet systems. CONCLUSIONS: SRT may be not disadvantageous compared to the classic PT from the impact on the glycolytic activity caused by the ischaemia.Level of evidence II.

Direct medical costs and their predictors in the EMAR-II cohort: "Variability in the management of rheumatoid arthritis and spondyloarthritis in Spain". / Costes médicos directos y sus predictores en la cohorte "Variabilidad en el manejo de la artritis reumatoide y las espondiloartritis en España".

OBJECTIVE: To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. METHODS: A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naïve, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models. RESULTS: We included 1,095 RA patients, 26% male, mean age of 62±14 years. Mean of direct medical costs per patient was €24,291±€45,382. Excluding biological drugs, the average cost per patient was €3,742±€3,711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P=.02) and disease activity (P=.004). In the biologic-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). CONCLUSION: Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.

Orthopedic surgery in rheumatoid arthritis in the era of biologic therapy.

OBJECTIVE: To analyze sociodemographic and clinic-related factors associated with the use of orthopedic surgical procedures in rheumatoid arthritis (RA), focusing on the potential role of new biologic therapies. METHODS: A retrospective medical record review was performed in a probability sample of 1272 patients with RA from 47 units distributed in 19 Spanish regions. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol. RESULTS: A total of 94 patients (7.4%) underwent any orthopedic surgery during their disease course, with a total of 114 surgeries; 47 (41.2%) of these surgeries were total joint replacement (TJR). The median time to first orthopedic procedure was 7.9 years from the onset of RA symptoms, and the rate of orthopedic surgery (excluding TJR) was 4.5 procedures per 100 person-years from the beginning of RA, while the rate of TJR was 2.25 interventions per 100 person-years. A higher risk of undergoing an orthopedic surgical procedure was associated with taking nonsteroidal antiinflammatory drugs (NSAID) in the previous 2 years, female sex, longterm disease, and the presence of extraarticular complications. The risk factors for undergoing a TJR were being old, having a longterm disease, and taking biologic therapies. CONCLUSION: In the era of biologics, our national audit found a low percentage of patients who underwent orthopedic surgery, probably reflecting a thorough management of the RA. Sociodemographic factors, longterm RA, extraarticular complications, and NSAID were associated with orthopedic surgery.

Management of rheumatoid arthritis in Spain (emAR II). Clinical characteristics of the patients.

BACKGROUND: There is a wide variability in the diagnostic and therapeutic methods in rheumatoid arthritis (AR) in Spain, according to prior studies. The quality of care could benefit from the application of appropriate clinical practice standards; we present a study on the variability of clinical practice. METHODS: Descriptive review of clinical records (CR) of patients aged 16 or older diagnosed with RA, selected by stratified sampling of the Autonomous Communities in two stages per Hospital Center and patient. Collected analysis of sociodemographic data, evolution, follow-up, joint count, reactants, function, job history, Visual Analogue Scales (VAS) and other. RESULTS: We obtained valid information of 1,272 RA patients. The ESR, CRP and rheumatoid factor (RF) were regularly used parameters. The percentages of missing data in tender (TJN) and swollen (SJN) joint counts were 8.2% and 9.6% respectively; regarding the VAS we found 53.6% (patient), 59.1% (pain), and 72% in the physician VAS. CONCLUSIONS: Despite having clinical practice guidelines on RA, there still exists a significant variability in RA management in our country.

Variability in resource consumption in patients with spondyloarthritis in Spain. Preliminary descriptive data from the emAR II study.

OBJECTIVE: Our objective was to describe the variability in the management of spondyloarthritis (SA) in Spain in terms of healthcare resources and their use. METHODS: A review of 1168 medical files of patients seen in randomly selected Spanish hospital rheumatology departments. We analyzed demographic variables and variables related to the consumption of health resources. RESULTS: The total number of visits to rheumatology were 5,908 with a rate of 254 visits/100 patient-years. The total number of visits to rheumatology specialty nurses was 775, with a rate of 39 visits/100 patient-years, and there were 446 hospitalizations, representing a rate of 22 per 100 patient-years. The number of admissions due to SA was 89, with a rate of 18 admissions/100 patient-years. Total visits to other specialists was 4,307 with a rate of 200/100 patient-years. The total number of orthopedic surgeries was 41, which leads to a rate of 1.8 surgeries/100 patient-years. CONCLUSIONS: The data regarding visits to the rheumatologist and prosthetic surgery of patients with in Spain is similar to most studies published in our environment, however, other aspects concerning the use of health resources are different compared to other countries. This data may help to understand and improve organizational aspects of management of SA in Spanish hospitals.

Characteristics of patients with spondyloarthritis followed in rheumatology units in Spain. emAR II study.

OBJECTIVE: To describe the main demographic and clinical features of patients with spondyloarthropaties in Spain. PATIENTS AND METHODS: Review of randomized clinical charts of patients with spondyloarthropaties with at least one visit to the rheumatologist in the previous two years. Information was collected on demographic and clinical data (duration of illness, diagnostic category, disease activity, extrarticular manifestations, comorbidity and work disability). RESULTS: 1,168 patients were included in the study. Their median age was 49.2 years (39.7-60.5), 68.0% were males, and median time of disease was 105.1 month (48.4-192.5). The diagnoses and clinical data such as the BASDAI were reported only in 34,0% of the patients. The most widely used measure of metrology, the Schober test, was missing in 37.7% of the clinical charts. The patients included had the following diagnoses: Ankylosing spondylitis (n = 629, 55.2%), Psoriatic arthritis (n= 253, 22.2%), Undifferentiated spondyloarthritis (n = 184, 16.1%), Arthritis associated to Inflammatory bowel disease (n= 50, 4.4%), and Reactive arthritis (n= 16, 1.4%). The most common extraarticular manifestations were psoriasis (20.8%), anterior uveitis (19.4%), and enthesitis (16.9%). Some kind of work disability was reported in 8.3% of the patients. CONCLUSIONS: Demographic and clinical characteristics of patients with spondyloarthropaties in Spain do not differ as a whole from other published studies, except for Undifferentiated Spondyloarthritis, which was more likely in our patients than in other studies. The quality of the records of activity in the clinical charts could be improved.

[Justification to health managers: cost-benefit of osteoporosis management]. / Justificación delante del gerente: coste-beneficio del manejo de la osteoporosis.

Medicines are strictly regulated and controlled until they reach the patients. Once in the market, the mechanisms governing their use are very complex due to the large number of actors playing different roles. It is necessary to extend an evaluation culture among all involved and to make economic analysis a structured part of decisions made by physicians and health managers. Since physicians occupy a central place in this market of medicines, it is necessary that they assume their responsibility by actively participating in this evaluation.

Prognostic factors in short-term disability due to musculoskeletal disorders.

OBJECTIVE: To identify factors associated with poor outcome in temporary work disability (TWD) due to musculoskeletal disorders (MSDs). METHODS: We conducted a secondary data analysis of a 2-year randomized controlled trial in which all patients with TWD due to MSDs in 3 health districts of Madrid (Spain) were included. Analyses refer to the patients in the intervention group. Primary outcome variables were duration of TWD and recurrence. Diagnoses, sociodemographic, work-related administrative, and occupational factors were analyzed by Cox proportional hazards models. RESULTS: We studied 3,311 patients with 4,424 TWD episodes. The following were independently associated with slower return to work: age (hazard ratio [HR] 0.99, 95% confidence interval [95% CI] 0.98-0.99), female sex (HR 0.84, 95% CI 0.78-0.90), married (HR 0.90, 95% CI 0.83-0.97), peripheral osteoarthritis (HR 0.77, 95% CI 0.6-0.9), sciatica (HR 0.59, 95% CI 0.54-0.65), self-employment (HR 0.56, 95% CI 0.48-0.65), unemployment (HR 0.41, 95% CI 0.28-0.58), manual worker (HR 0.86, 95% CI 0.79-0.94), and work position covered during sick leave (HR 0.84, 95% CI 0.77-0.92). The factors that better predicted recurrence were peripheral osteoarthritis (HR 1.75, 95% CI 1.14-2.6), inflammatory diseases (HR 1.66, 95% CI 1.009-2.72), sciatica (HR 1.30, 95% CI 1.08-1.56), indefinite work contract (HR 1.43, 95% CI 1.14-1.75), frequent kneeling (HR 1.39, 95% CI 1.15-1.69), manual worker (HR 1.19, 95% CI 1.003-1.42), and duration of previous episodes (HR 1.003, 95% CI 1.001-1.005). CONCLUSION: Sociodemographic, work-related administrative factors, diagnosis, and, to a lesser extent, occupational factors may explain the duration and recurrence of TWD related to MSD.

Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis.

OBJECTIVE: To reevaluate the efficacy and safety of adjunctive low-dose methotrexate (MTX) in giant cell arteritis (GCA). METHODS: An individual patient data meta-analysis of 3 randomized placebo-controlled trials in patients with newly diagnosed GCA was performed. Treatment consisted of initial high-dose corticosteroids and randomly assigned oral MTX therapy (7.5-15 mg/week) or placebo. Time-to-event outcomes were compared between groups using Cox proportional hazards models stratified by trial, and continuous outcomes were compared by calculating weighted mean differences. RESULTS: The combined data set comprised 161 patients, of whom 84 received MTX and 77 received placebo. The mean duration of followup was 54.7 weeks (SD 39.2 weeks). Hazard ratios (HRs) for a first and second relapse of GCA were 0.65 (P = 0.04) and 0.49 (P = 0.02), respectively, in patients receiving MTX as compared with patients receiving placebo. Accordingly, a predicted 3.6 individuals (95% confidence interval [95% CI] 2.2-56.8) and 4.7 individuals (95% CI 3.3-21.9) need to be treated with MTX to prevent the occurrence of one first or one second relapse, respectively, up to 48 weeks. Use of MTX resulted in a reduction in the corticosteroid cumulative dose by 842 mg within 48 weeks (P < 0.001). Moreover, MTX treatment was associated with a higher probability of achieving sustained discontinuation of corticosteroids for > or =24 weeks (HR 2.84, P = 0.001). Dropout rates and occurrence of adverse events did not differ between treatment groups. CONCLUSION: In GCA, adjunctive treatment with MTX lowers the risk of relapse and reduces exposure to corticosteroids. These findings indicate that MTX could be considered as a therapeutic option in addition to standard-of-care treatment with corticosteroids for patients with GCA.

Variability in the use of orthopedic surgery in patients with rheumatoid arthritis in Spain.

OBJECTIVE: To analyze sociodemographic and clinic-associated factors of patients with rheumatoid arthritis (RA) undergoing any orthopedic surgery (AOS) and total joint replacement (TJR) in Spain. METHODS: A retrospective medical record review was performed in a probabilistic sample of 1379 RA patients from 46 centers distributed in 16 of 19 regions in Spain. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol. Gross domestic product (GDP) data were obtained from the National Statistical Index. RESULTS: Of 1379 patients, a total of 358 (26%) underwent one or more joint surgeries, and 194 (14%) had a TJR. The median time to first orthopedic procedure was 12.5 years from presentation of RA and the estimated rate was 5.6 surgeries per 100 person-years. The rate of AOS was increased in women, patients with RA with extraarticular complications, with longterm RA (> 10 yrs), with functional grade III-IV, and with persistent inflammatory disease. The risk factors for undergoing a TJR were longterm RA, functional grade III-IV, and extraarticular complications. Patients from regions with higher GDP per capita were more likely to undergo a procedure. CONCLUSION: Clinical variables reflecting disease activity and severity are predictors of orthopedic surgery, but geographic and socioeconomic variables were also independently associated with the rate of orthopedic surgery.

Musculoskeletal work disability for clinicians: time course and effectiveness of a specialized intervention program by diagnosis.

OBJECTIVE: To evaluate how an intervention program modifies the clinical course of work disability in musculoskeletal diagnoses. METHODS: All patients with temporary work disability related to musculoskeletal disorders (MSDs) in 3 health districts of Madrid, Spain were randomized into standard care (control group) or the intervention group. Intervention consisted of a specific program, run by rheumatologists, following detailed proceedings. Inclusion and followup lasted 12 months each. According to the cause, every temporary work disability episode was classified into 11 syndrome categories. For each we calculated efficacy, as the difference between groups in the number of days on sick leave per temporary work disability episode; relative efficacy, or the percentage of days saved in the intervention group; and time of maximum program effect. Analyses were performed on an intent-to-treat basis. Survival techniques were run and results were expressed as the hazard ratio (HR) in the intervention versus control group. RESULTS: A total of 13,077 patients were included, generating 16,297 temporary work disability episodes. The most frequent cause was back pain. Temporary work disability episodes were significantly shorter in the intervention group than in the controls in all syndrome categories except knee pain (excluding osteoarthritis). Program relative efficacy varied from 28-72%. The program was highly efficacious in carpal tunnel syndrome (HR 2.09, 95% confidence interval [95% CI] 1.17-3.75), peripheral osteoarthritis (HR 1.58, 95% CI 1.14-2.19), and inflammatory diseases (HR 1.52, 95% CI 1.09-2.12). The maximum effect of the program always took place within the first 2 months. CONCLUSION: The implementation of this type of specialist-run, protocol-based early intervention program would be very beneficial in the treatment of patients with work disability related to MSDs, except for those with knee pain (excluding osteoarthritis).

[Reduction in time until first treatment with disease modifying treatment in patients with rheumatoid arthritis]. / Disminución del tiempo hasta el primer tratamiento con fármacos modificadores de la enfermedad en pacientes con artritis reumatoide.

OBJECTIVE: To analyze changes in the lag time to first disease modifying antirheumatic drug (DMARD) prescription since onset of symptoms of rheumatoid arthritis (RA) over the last 2 decades in Spain. PATIENTS AND METHOD: Review of medical records of 865 patients diagnosed with RA living in Spain and attended in specialty care settings of the National Health System. The principal variable was the lag time between the onset of symptoms of RA and the date of first DMARD therapy prescription. Analyses were performed by year and five-year periods and differences between groups were assessed by χ(2) test, Student t test and analysis of variance. RESULTS: Sociodemographic and clinical characteristics corresponded to a typical cross-sectional population of patients diagnosed with RA. The median lag time between symptom onset and first DMARD therapy was 14 months (6-36) for the whole group. However, a significant shortening of time to first DMARD was observed over the last two decades (-4.59±0.2 months by year; P<001). Shortening of time to first DMARD was mainly due to a shortening of time to first visit with specialists since onset of symptoms with a smaller decrease in time from first visit to first prescription of a DMARD agent. CONCLUSIONS: A significant shortening in the lag time to first DMARD therapy was observed over the last 2 decades in Spain, being a significant reduction in the time to first visit with a specialists its major cause.

A health system program to reduce work disability related to musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders (MSDs) are a frequent cause of work disability, accounting for productivity losses in industrialized societies equivalent to 1.3% of the U.S. gross national product. OBJECTIVE: To evaluate whether a population-based clinical program offered to patients with recent-onset work disability caused by MSDs is cost-effective. DESIGN: Randomized, controlled intervention study. The inclusion and follow-up periods each lasted 12 months. SETTING: Three health districts in Madrid, Spain. PATIENTS: All patients with MSD-related temporary work disability in 1998 and 1999. INTERVENTION: The control group received standard primary care management, with referral to specialized care if needed. The intervention group received a specific program, administered by rheumatologists, in which care was delivered during regular visits and included 3 main elements: education, protocol-based clinical management, and administrative duties. MEASUREMENTS: Efficacy variables were 1) days of temporary work disability and 2) number of patients with permanent work disability. All analyses were done on an intention-to-treat basis. RESULTS: 1,077 patients were included in the study, 7805 in the control group and 5272 in the intervention group, generating 16,297 episodes of MSD-related temporary work disability. These episodes were shorter in the intervention group than in the control group (mean, 26 days compared with 41 days; P < 0.001), and the groups had similar numbers of episodes per patient. Fewer patients received long-term disability compensation in the intervention group (n = 38 [0.7%]) than in the control group (n = 99 [1.3%]) (P < 0.005). Direct and indirect costs were lower in the intervention group than in the control group. To save 1 day of temporary work disability, 6.00 dollars had to be invested in the program. Each dollar invested generated a benefit of 11.00 dollars. The program's net benefit was in excess of 5 million dollars. LIMITATIONS: The study was unblinded. CONCLUSIONS: Implementation of the program, offered to the general population, improves short- and long-term work disability outcomes and is cost-effective.

Increased risk of tuberculosis in patients with rheumatoid arthritis.

OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.

Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study.

OBJECTIVE: To analyze the annual cost of rheumatoid arthritis (RA) and its predictive factors. METHODS: Data were obtained from a 12-month retrospective cohort of 201 RA patients, randomly selected from a rheumatology registry, through a structured interview and records of the Central Information System of the hospital. Results were divided into direct, indirect, and total costs in 2001 US dollars. A sensitivity analysis was performed. Multiple linear regression models for the different types of costs were carried out. RESULTS: The total cost was US dollars 2.2 million per year, with a cost attributable to RA of US dollars 2.07 million per year. The average cost per patient was US dollars 10419 per year (ranging from US dollars 7914 per patient per year in the best scenario to US dollars 12922 per patient per year in the worst case). Direct costs represent nearly 70% of total costs. We found an average increment in total costs of US dollars 11184 per year per unit of Health Assessment Questionnaire (HAQ) score (P < 0.0001) and an average annual increment of US dollars 621 per year of disease (P < 0.0001). After adjustment, the HAQ score, inability to perform housework tasks, and being permanently disabled for work were the only predictors of high costs. CONCLUSION: Our data show a remarkable economic impact of RA over society and link the costs of the disease to its consequences in terms of functional disability, work disability, and housework disability.

[Variations in the drug treatment of rheumatoid arthritis in Spain]. / Variabilidad en el tratamiento farmacológico de la artritis reumatoide en España.

BACKGROUND: Variations in the use of healthcare resources can result in differences in the outcome of rheumatoid arthritis (RA). The emAR study was developed to determine variations in the management of socio-sanitary resources, including drugs use, in patients with this disorder. PATIENTS AND METHOD: The clinical records of 1,379 patients, randomly selected among all RA patients attended in Spanish hospitals, were reviewed. Information about prescription of disease modifying anti-rheumatic drugs (DMARD), non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, analgesics, gastric protectors and drugs for osteoporosis was collected. In addition, socio-demographic- and disease-related information, as well as data from hospitals, medical units and responsible physicians were also obtained in each patient. RESULTS: There was a high level of DMARD and NSAID prescription that was associated with patient or disease characteristics. Treatment with corticosteroids, as well as with the remaining drugs, showed a substantial regional variability, which may be related to physician-associated variables as well as to patient- and disease-associated characteristics. CONCLUSIONS: Variability in the management of therapeutic resources in RA patients mainly depends on the characteristics of the patient or the disease. There is also a variation that is influenced by physician's characteristics; in some cases, the available scientific evidence may not support this variability.