The Avise Lupus Test and Cell-bound Complement Activation Products Aid the Diagnosis of Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise Lupus test, has been recently commercialized and validated in clinical studies. OBJECTIVES: To evaluate the use of the Avise Lupus test by community rheumatologists. METHODS: The study is a longitudinal, case-control, retrospective review of medical charts. Cases had a positive test result, and controls had a negative result; all patients were anti-nuclear antibodies (ANA) positive but negative for SLE-specific autoantibodies. Features of SLE, diagnosis, and medications at two time points were recorded. RESULTS: Twenty of the 23 cases (87%) and 4 of the 23 controls (17%) were diagnosed with SLE (sensitivity=83%; specificity=86%). More cases than controls (43% vs. 17%) fulfilled 4 American College of Rheumatology (ACR) classification criteria of SLE. Sensitivity of the test was significantly higher than the ACR score (83% vs. 42%, p=0.006). A higher percentage of patients who met the classification criteria had elevated cell-bound complement activation products (CB-CAPs) compared to patients who did not. Anti-rheumatic medications were used in a higher percentage of cases than controls (83% vs. 35% at baseline, p=0.002), suggesting that cases were treated more aggressively early on. CONCLUSION: A positive Avise Lupus test result aids in formulating a SLE diagnosis when diagnosis based on standard-of-care tests and clinical features may be challenging, and impacts patient management. Prospective studies will be performed to better evaluate the clinical utility of the test and of CB-CAPs as biomarkers of SLE.

Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study.

OBJECTIVE: Evaluate efficacy of infliximab with response-driven dosing in patients with active RA. RESEARCH DESIGN AND METHODS: Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26. CLINICAL TRIAL REGISTRATION: NCT 00714493, EudraCT 2007-003288-36. RESULTS: Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change -1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients. CONCLUSION: Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial. KEY LIMITATIONS: Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.

Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheumatoid Arthritis Disease-Modifying Anti-Rheumatic Drug Intervention and Utilization Study) study.

OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.