Treatment Of Early Rheumatoid Arthritis Research Articles

Metabolic effects of high‐dose prednisolone treatment in early rheumatoid arthritis: Balance between diabetogenic effects and inflammation reduction

To investigate the dose-related effects of glucocorticoid treatment on glucose tolerance, beta cell function, and insulin sensitivity in patients with early active rheumatoid arthritis (RA). A randomized, controlled, single-blind trial was conducted in 41 patients with early active RA. At the beginning of the trial patients had not been treated for their RA, and were randomized to begin treatment with prednisolone at 60 mg/day or 30 mg/day. Before and at the end of 1 week of treatment, a frequently sampled oral glucose tolerance test was performed. The glucose area under the curve (AUC(G) ) was calculated. In addition, beta cell function and insulin sensitivity parameters were computed. Patients (mean ± SD age 55.5 ± 14.8 years and 54.2 ± 12.6 years in the prednisone 60 mg/day and prednisone 30 mg/day groups, respectively; body mass index 24.5 ± 4.1 kg/m(2) and 25.4 ± 4.2 kg/m(2) , respectively) had active disease at baseline (mean ± SD Disease Activity Score in 44 joints 4.1 ± 0.7 and 4.0 ± 0.8, respectively; median C-reactive protein [CRP] level 14 mg/liter [interquartile range 6-34] and 19 mg/liter [interquartile range 3-39], respectively). In addition, 56% of the patients had impaired glucose tolerance at baseline, and 7% were found to have previously unrecognized type 2 diabetes mellitus (DM). Associations of the AUC(G) with erythrocyte sedimentation rate (β = 2.430 [95% confidence interval 0.179-4.681], P = 0.04) and with CRP level (β = 2.358 [95% confidence interval 0.210-4.506], P = 0.03) were demonstrated. Treatment with prednisolone at both dosages reduced CRP levels significantly. The incidence of type 2 DM increased to 24% (P < 0.001) (evenly distributed across the groups). The mean AUC(G) did not change in either treatment arm. Beta cell function improved during prednisone treatment at 60 mg/day (P = 0.02) and at 30 mg/day (P = 0.04). Disease duration was associated with changes in the AUC(G) (β = 3.626 [95% confidence interval 1.077-6.174], P = 0.007) and with deterioration of the glucose state (odds ratio 1.068 [95% confidence interval 1.017-1.122], P = 0.009). In this study, short-term treatment with prednisolone 60 mg or 30 mg per day improved disease activity without deterioration of glucose tolerance in patients with active RA. However, due to individual differences, monitoring is recommended.

A Focus on the Diagnosis of Early Rheumatoid Arthritis

Nowadays it is worldwide accepted that early diagnosis and early treatment of Rheumatoid Arthritis (RA) can improve the prognosis in most of patients. In this way, the 2010 ACR/EULAR Rheumatoid Arthritis classification criteria have shown to be more sensitive than the ACR 1987 criteria and include better patients with early RA. Other important point to focus on is to identify predictive factors for outcome, in order to propose a more aggressive treatment for early RA patients who could develop a persistent and/or erosive disease. The presence of Rheumatoid Factors (RF) and Anticitrullinated peptides antibobies (ACPA), as well as the duration of the disease at the time of diagnosis, are independent risk factors for the development of erosive RA. As for imaging, both traditional X-ray and Magnetic Resonance Imaging (MRI) highlight respectively the Rapid Radiological Progression (RRP) and the presence of bone edema which are associated to a more aggressive disease. In the last years, the musculoskeletal ultrasonography (MSUS) has emerged as a useful imaging technique since it allows to identify synovitis and bone alteration earlier than the radiological examination. Interating clinical, serological and imaging data the clinician can define the effective disease activity of each patient.

Relationship between early bone mineral density changes and long‐term function and radiographic progression in rheumatoid arthritis

To ascertain whether bone mineral density loss during the first year of treatment for early rheumatoid arthritis (RA) as assessed by dual x-ray absorptiometry (DXA) is associated with long-term function, quality of life, and radiographic progression. Early RA patients, prior to commencing disease-modifying antirheumatic drug therapy, underwent evaluation with DXA scans of both hands, femoral neck, and lumbar spine at the time of diagnosis, then at 1 year and final followup at >6 years. Clinical and laboratory data and hands and feet radiographs were obtained at baseline and final followup. Sixty-four patients were assessed. At baseline, median disease duration was 6 months, mean 28-joint Disease Activity Score was 5.85, and median Health Assessment Questionnaire score was 1.38. Median followup was 6.4 years (range 5.1-7.2 years). For erosion scores, 86% of patients with hand bone density loss above the smallest detectable change after 1 year progressed versus 55% of those with no hand bone density loss (P = 0.006). However, baseline radiographs showed a similar strength of association. Eighty-four percent of patients with erosions at baseline had erosion progression versus 57% of those with no baseline erosions (P = 0.021). Additionally, first-year bone density loss was not associated with function and quality of life status at followup. Hand bone loss during the first year of treatment in early RA, as assessed with DXA, was associated with a high likelihood of radiographic progression; however, in the current study this was not superior to baseline radiographs. Furthermore, it was not associated with patient-reported outcomes.

Standard treatment in daily clinical practice for early rheumatoid arthritis improved disease activity from 2001 to 2006

We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher’s exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort (p < 0.001) and from 4.1 to 3.1 in the 2006-cohort (p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 (p < 0.02) in the 2001-cohort and from 0.71 to 0.41 (p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort (p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006.

A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study)

In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple institutes who fulfilled the American Rheumatism Association 1987 revised criteria for the classification of RA, and followed the clinical results of disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the aim of developing therapeutic guidelines using the disease activity score 28 (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC), one of the most widely used DMARDs in Japan. Eighty-one patients with early RA who had not previously been treated with DMARDs were suitable for BUC therapy as first-choice treatment. After 24 months of treatment, at least moderate improvement was seen in 87.5% of patients using the DAS28 erythrocyte sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of DAS28 (ESR) <2.6. The 24-month BUC continuation rate was 60.5% (49/81, monotherapy + combination therapy), of which 59.2% (29/49) were on BUC monotherapy. From the efficacy and safety viewpoints alike, BUC was useful as first-choice treatment for early RA.

Standard treatment in daily clinical practice for early rheumatoid arthritis improved disease activity from 2001 to 2006

We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher's exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort (p < 0.001) and from 4.1 to 3.1 in the 2006-cohort (p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 (p < 0.02) in the 2001-cohort and from 0.71 to 0.41 (p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort (p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006.

Erratum to: A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study)

(2011). Erratum to: A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study) Modern Rheumatology: Vol. 21, No. 3, pp. 258-259.

Naïve T cells predict MTX induced remission in early arthritis

BackgroundWe previously reported that immunological parameters can predict 6 month response to treatment in early rheumatoid arthritis independently of the drug received. Normal naïve CD4 T cells frequency, notably predicted...

The value of early intervention in RA—a window of opportunity

Rheumatoid arthritis (RA) is associated with progressive joint destruction, with functional status influenced by both disease activity and radiographic progression. The case for early aggressive treatment of RA is based on large amounts of good data in many countries. Studies with conventional disease-modifying anti-rheumatic drugs in early RA have shown improved outcomes compared with later treatment, especially if an aggressive approach with combinations of drugs is used. Early intervention with tumour necrosis factor (TNF) inhibitors has been shown to improve clinical outcomes, induce remission and prevent radiographic progression. It also improves patients' functional status, health-related quality of life, and reduces fatigue. Patients with RA have reduced productivity, an increased number of lost work days and retire early; enabling patients to work should be at the core of a therapy's cost-effectiveness. Introduction of anti-TNF therapy early in RA has been shown to decrease job loss and reduce the amount of working time missed. Although the drug costs of initial treatment with combination therapy including a TNF inhibitor are high, these may be compensated by the reduction in lost productivity, making such a strategy cost-effective overall. In addition, some patients who respond well to combination therapy may be able to stop the TNF inhibitor. It is important to assess the benefits of any intervention not just to healthcare costs but to society as a whole, and physicians should be advocates for optimal access to effective therapies for their patients.

Treatment of Early Rheumatoid Arthritis: Concepts in Management

The early diagnosis and treatment of rheumatoid arthritis (RA) are important goals for rheumatologists. This article provides a review of the literature describing evolving concepts in the treatment of early RA, studies that evaluate treatment strategies using a predefined target, and methods to identify patients who are at higher risk for progressive joint damage. We conducted a PubMed search for randomized trials using the terms "early rheumatoid arthritis" and subsequently "tight control" to compare the outcomes of studies using early intervention with biologics and disease-modifying antirheumatic drugs (DMARDs) in early RA and also to compare outcomes of strategies of treatment using a predefined target. The study designs and outcomes of clinical trials of DMARDs and biologic agents in early RA are presented. Early, prompt therapy with combination DMARDs or biologics combined with methotrexate leads to improved outcomes for patients with early RA. In studies where treatment was targeted to a specific outcome, such as remission, the target was achieved more often with targeted treatment than when patients received routine care. Patients who are more likely to experience a rapid disease course that is associated with joint destruction can be identified based on clinical and laboratory variables shown to be predictors of rapid progression. Early assessment and close monitoring of patients with early RA, targeting remission where possible, are important to optimize long-term outcomes. Specific treatment can be selected from among the many proven therapies to obtain the best results for the individual patient.

The long-term impact of early treatment of rheumatoid arthritis on radiographic progression: a population-based cohort study

To measure the long-term rate of radiographic progression in a cohort of patients treated early vs late with conventional DMARDs. The long-term rate of radiographic progression in patients included in the Swiss clinical quality management in rheumatoid arthritis (SCQM-RA) registry who initiated treatment with conventional DMARDs within the first year of symptom onset (early DMARD) vs patients who initiated treatment 1-5 years after symptom onset (late DMARD). Radiographic progression was assessed in 38 joints using a validated score (Ratingen Score). The rate of progression was calculated using a multivariate regression model for longitudinal data, adjusting for potential confounders. A total of 970 RA patients were included. The 368 patients in the early DMARD group started therapy after a median symptom duration of 6 months, whereas the 602 patients in the late DMARD group initiated therapy after median 2.5 years. RF, MTX use and other risk factors for erosive disease progression were similar between the two groups. However, the estimated rate of radiographic progression at baseline was higher in the early DMARD vs the late DMARD group (1.8 vs 0.6, P < 0.01). In spite of this, the long-term rate of radiographic progression was significantly lower in the early DMARD group after adjustment for confounding factors (-0.35 at 5 years, P = 0.012). This result supports the concept of a therapeutic window of opportunity early in the disease course and suggests that early initiation of DMARD therapy results in a long-lasting reduction of radiographic damage.

Treatment of early arthritis using arthrofoon (ultra-low doses of antibodies to tumor necrosis factor-α)

The main aim of treatment of early rheumatoid arthritis (RA) should be to achieve clinical remission to prevent structural damage and physical disability. Arthrofoon modifies production/activity of endogenous inhibitors of tumor necrosis factor-α (TNF-α). The sublingual rout is the most acceptable to ambulatory treatment because it does not produce the adverse reactions associated with intravenous therapy. The treatment with arthrofoon in outpatient with early RA is analyzed here. This report is devoted to the 28-year-old Russian woman who received arthrofoon due to suspicion of early RA. The strategy of early prescription of ultra-low doses of TNF-α antibody within two years was confirmed by the clinical improvement and delay of radiological disease progression in patient with undifferentiated arthritis or probable RA initially.

A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study)

In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple institutes who fulfilled the American Rheumatism Association 1987 revised criteria for the classification of RA, and followed the clinical results of disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the aim of developing therapeutic guidelines using the disease activity score 28 (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC), one of the most widely used DMARDs in Japan. Eighty-one patients with early RA who had not previously been treated with DMARDs were suitable for BUC therapy as first-choice treatment. After 24 months of treatment, at least moderate improvement was seen in 87.5% of patients using the DAS28 erythrocyte sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of DAS28 (ESR) <2.6. The 24-month BUC continuation rate was 60.5% (49/81, monotherapy + combination therapy), of which 59.2% (29/49) were on BUC monotherapy. From the efficacy and safety viewpoints alike, BUC was useful as first-choice treatment for early RA.

Tight control in early RA pays off in the long run

Clinical trials demonstrate that intensive treatment of early rheumatoid arthritis with a combination of DMARDs improves short-term outcomes. an extension study from a pivotal trial has now shown that such intensive early therapy can achieve a reduction in the rate of erosive progression over a period of 11 years.

Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months

IntroductionRheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy.MethodsForty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model.ResultsPatients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups.ConclusionsInfliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The increase of adiponectin may partially explain the reduced frequency of cardiovascular diseases found when disease activity is reduced in RA.Trial registrationISRCTN39045408.

A prospective study for outcome and prediction of early arthritis: a tertiary care centre observation

Introduction Early undifferentiated arthritis has varied outcome: majority remits spontaneously and about 1/3 rdevolve into rheumatoid arthritis (RA). Objective To find out the clinical feature of early arthritis, its outcome, predictors of its evolution into rheumatoid arthritis and of its spontaneous remission and the outcome of treatment of early rheumatoid arthritis. Method Fifty-three patients (37 females) were recruited. Logistic-regression analysis was done to find out independent predictors of early arthritis evolving into RA or remitting spontaneously and the Receiving Operating Characteristic curve analysis was done to examine the validity of the Prediction rule. Result About half of the patients had spontaneous remission and rest evolved into RA. The majority (31.4%) of patients with early arthritis presented with symmetric arthritis involving both upper and lower limbs. A low DAS28 (odds ratio 0.384, P=0.002) at presentation was the predictor of evolution into RA whereas anti-CCP antibody negativity (odds ratio 0.222, P= 0.044) was predictor of spontaneous resolution. Conclusion The anti-CCP antibody predicted disease remission whereas low disease activity predicted disease persistence. Larger sample size with longer duration of follow-up is needed.

Avaliação prospectiva da qualidade de vida em uma coorte de pacientes com artrite reumatoide inicial

Few studies have prospectively assessed the tools used to measure quality of life, both generic and specific, in patients with early rheumatoid arthritis (RA). The objective of this study was to characterize a population of patients with early RA (less than 12 months after symptom onset at the time of the diagnosis) prospectively followed for the pattern of responses to questionnaires addressing quality of life, the Health Assessment Questionnaire (HAQ) and Medical Outcomes Study SF-36 Health Survey (SF-36). Forty patients with early RA at the time of diagnosis, treated with a standard treatment regimen, were prospectively followed for 3 years. Demographic and clinical data were recorded, and HAQ and SF-36 questionnaires were applied at baseline and after 3, 6, 12, 18, 24, and 36 months. Paired Student t test and Wilcoxon test were used for comparisons (significance level of 5%). The mean age was 45 years, with a prevalence of the female gender (90%). The average score of the initial HAQ was 1.89, with a progressive decline to 0.77 in the third year (P < 0.0001). Most domains of the SF-36 questionnaire presented significant improvement during the three years of follow-up, except for general health and vitality. In this population of patients with early RA at the time of diagnosis, the results showed significant impact on quality of life at the time of diagnosis, as measured by HAQ and SF-36 questionnaires. The early treatment of RA seems to be associated with improved health-related quality of life reported by patients.

Leflunomide in the treatment of patients with early rheumatoid arthritis—results of a prospective non-interventional study

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (≤1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of ≤5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 ≤ 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies.

Análisis farmacoeconómico de Metoject ® en el tratamiento de la artritis reumatoide en España

Objectives The aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject ®) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain. Methods A cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied. Results The cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject ® went from 25,173 to 35,807 € at 5 years and from 19,056 to 25,351 € for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175 €/QALY gained, and for patient lifetime from 22,514 to 29,848 €/ QALY gained. Conclusions Additional costs of Metoject ® with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject ® could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.

Modulation of gene expression by leflunomide and prednisone during treatment of early rheumatoid arthritis

Many genes encoding human leucocyte antigen molecules or involved in the activation and resistance of apoptosis of T cells have a role in the susceptibility to rheumatoid arthritis (RA) and...