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The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA).To determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy.A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model.The RACAT trial and sources from the literature.Patients with active RA despite at least 12 weeks of methotrexate therapy.24 weeks and lifetime.Societal and Medicare.Etanercept-methotrexate first versus triple therapy first.Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).The within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient.Considering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions.Data on the long-term benefit of triple therapy are uncertain.Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit.The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health-American Recovery and Reinvestment Act.

Objective To create a pediatric rheumatology Top 5 list as part of the American Board of Internal Medicine Foundation's Choosing Wisely campaign. Methods Delphi surveys of a core group of representative pediatric rheumatology providers from across North America generated candidate Top 5 items. Items with high content agreement and perceived to be of prevalent use and of high impact were included in a survey of all American College of Rheumatology (ACR) members who identified themselves as providing care to pediatric patients. Items with the highest ratings were subjected to literature review and further evaluation. Results A total of 121 candidate items were proposed in the initial Delphi survey and were reduced to 28 items in subsequent surveys. These 28 items were sent to 1,198 rheumatology providers who care for pediatric patients, and 397 (33%) responded. Based upon survey data and literature review, the Top 5 items were identified. These items focused on testing for antinuclear antibodies, autoantibody panels, Lyme disease, methotrexate toxicity monitoring, and use of routine radiographs. Conclusion The ACR pediatric rheumatology Top 5 is one of the first pediatric subspecialty–specific Choosing Wisely Top 5 lists and provides an opportunity for patients and providers to discuss appropriate use of health care in pediatric rheumatology.

Objective To assess the safety of tacrolimus used in combination with oral methotrexate (MTX) to control the signs and symptoms of rheumatoid arthritis (RA) in patients whose disease remains active despite treatment with MTX. Methods This was a multicenter open-label study conducted at 13 US sites. Eighty patients who at baseline had active RA (mean tender/painful joint count 29.4, mean swollen joint count 17.4, mean erythrocyte sedimentation rate 25.1 mm/hour) despite treatment for ≥1 month with a stable, maximally tolerated dosage of oral MTX (≤20 mg/week, median dosage 15 mg/week, range 5–20 mg/week) were enrolled and received 3 mg/day tacrolimus as a single oral dose once per day for 6 months while continuing to receive MTX at the existing stable dosage. All other disease-modifying antirheumatic drugs were discontinued; stable dosage of nonsteroidal antiinflammatory drugs and oral corticosteroids (≤10 mg/day prednisone or its equivalent) were allowed. All 80 patients received at least one dose of the study drug and were included in the primary safety and efficacy analyses. Seventy-five patients had at least one postbaseline efficacy assessment, and 63 patients (78.8%) completed the study. The primary clinical response criterion was the American College of Rheumatology definition of 20% improvement (ACR20) at the end of treatment. Results Seven patients (12.5%) withdrew from the study because of adverse events possibly or probably related to treatment with tacrolimus, and 4 (5.0%) withdrew due to lack of efficacy. One serious adverse event (pancreatitis) was possibly related to tacrolimus treatment. The mean (±SD) creatinine (Cr) level increased from 0.74 ± 0.16 mg/dl at baseline to 0.81 ± 0.22 mg/dl (P < 0.001) at the end of treatment. Twenty-three patients (28.8%) had a ≥30% maximum increase in the Cr level from baseline during the study, with the Cr level in 3 patients (3.8%) exceeding the range considered normal for their age and sex. The maximum Cr level during the study was 1.8 mg/dl. The ACR20 clinical response rate at the end of treatment was 52.5% (95% confidence interval 41.6–63.4%). Conclusion In patients whose active RA persists despite treatment with MTX, tacrolimus in combination with MTX is safe and well-tolerated and provides clinical benefit.

To create a pediatric rheumatology Top 5 list as part of the American Board of Internal Medicine Foundation's Choosing Wisely campaign.Delphi surveys of a core group of representative pediatric rheumatology providers from across North America generated candidate Top 5 items. Items with high content agreement and perceived to be of prevalent use and of high impact were included in a survey of all American College of Rheumatology (ACR) members who identified themselves as providing care to pediatric patients. Items with the highest ratings were subjected to literature review and further evaluation.A total of 121 candidate items were proposed in the initial Delphi survey and were reduced to 28 items in subsequent surveys. These 28 items were sent to 1,198 rheumatology providers who care for pediatric patients, and 397 (33%) responded. Based upon survey data and literature review, the Top 5 items were identified. These items focused on testing for antinuclear antibodies, autoantibody panels, Lyme disease, methotrexate toxicity monitoring, and use of routine radiographs.The ACR pediatric rheumatology Top 5 is one of the first pediatric subspecialty-specific Choosing Wisely Top 5 lists and provides an opportunity for patients and providers to discuss appropriate use of health care in pediatric rheumatology.

This Phase III, placebo and active controlled, multicenter trial evaluated the efficacy and safety of meloxicam 7.5, 15, and 22.5 mg daily for the treatment of rheumatoid arthritis (RA).A 12 week, randomized, double blind, double dummy, parallel group trial compared daily oral meloxicam 7.5, 15, and 22.5 mg to placebo (negative control) and diclofenac 75 mg BID (positive control). A total of 894 patients (18 years of age with confirmed RA who flared following an NSAID-free period) were randomized to be treated. Baseline scores for all endpoints were similar among the treatment groups. Patient assessments were at 0, 2, 4, 8, and 12 weeks or early termination.All treatment groups demonstrated significant improvement from baseline (p0.001). Meloxicam 7.5 and 22.5 mg was significantly superior to placebo in all 5 primary efficacy endpoints (swollen joint count, tender joint count, patient pain, patient and physician global; all p0.05). Diclofenac 150 mg was superior to placebo for 4 of 5 primary efficacy measures (all but swollen joint count; p0.05) and meloxicam 15 mg was superior for 3 of 5 primary endpoints (patient pain and patient and physician global). AUC of patient global, patient pain, and modified Health Assessment Questionnaire demonstrated dose-response (p0.04), while AUC ACR20 showed a qualitative trend in the same direction. The rate of gastrointestinal (GI) events during the 12 week trial for all doses of meloxicam and diclofenac did not differ significantly from placebo (23.2-32.0%). GI withdrawals were comparable and not significantly different across all treatment groups (4.3-5.7%).This trial demonstrated a dose response relationship for meloxicam 7.5, 15, and 22.5 mg using AUC measurement of response for the treatment of RA. All 3 doses of meloxicam. and positive control, were effective in the treatment of RA. The overall incidence rate of GI events did not differ significantly from placebo in either the meloxicam treatment groups or the positive control.

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.

The cause of an acute arthritis can usually be determined on the basis of the history, physical examination, and evaluation of the synovial fluid.

Current medical management for established hemophilic arthritis is unsatisfactory and does not modify the eventual outcome. D-Penicillamine (PEN), an anti-inflammatory drug effective in rheumatoid arthritis, has not been evaluated in hemarthroses-induced joint disease. 83 NZ white rabbits had weekly intra-articular injections of citrated autologous blood (right knee) and citrated saline (left knee) for 6 months. PEN 15 mg or 50 mg/kg/da, IM, was begun early (day 1) or late (at 8 wks). Controls were saline treated rabbits. The animals were killed at 6 mo. Analysis included joint fluid WBC counts, gross and histologic examination of the synovia (acute and chronic inflammatory cells, synovial hyperplasia, and iron deposition). The saline-injected knees showed no inflammatory change and the blood-injected knees had iron deposition in all animal groups. The early high and low dose, and late low dose PEN treated groups showed no difference from untreated animals. Late high dose PEN treatment showed marked suppression of the synovitis. Four hemophiliacs with synovitis were given PEN, 5-10 mg/kg/da, p.o. for>2 months. All have had significant reduction in the synovial thickening with concurrent increased range-of-motion and decreased number of bleeds into the affected joint. These studies suggest that PEN is beneficial in the chronic arthritis induced by hemarthroses. Its anti-inflammatory mechanism is not known but may be inhibiting free radical formation, not by removing iron by its chelating ability.