Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial.

OBJECTIVES: Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. METHODS: The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). RESULTS: 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. CONCLUSIONS: MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. TRIAL REGISTRATION NUMBERS: EudraCT-number 2008-007225-39 and NCT01172639; Results.

Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis: Results From Two Belgian Nationwide Axial Spondyloarthritis Cohorts.

OBJECTIVE: To determine the link between extraarticular manifestations (EAMs) and baseline characteristics in patients with axial spondyloarthritis (SpA), and to define their potentially differential prognostic value in 2 large, independent Belgian axial SpA cohorts with distinct recruitment periods. METHODS: Information on demographic and clinical characteristics and extraarticular manifestations (EAMs) was obtained from patients with axial SpA originating from the (Be)Giant (Belgian Inflammatory Arthritis and Spondylitis) cohort, which includes consecutive axial SpA patients whose data have been collected since 2010, and from the ASPECT (Ankylosing Spondylitis Patients Epidemiological Cross-sectional Trial) cohort, a Belgian registry of cross-sectional data collected between February 2004 and February 2005 from consecutive patients with ankylosing spondylitis (AS) or probable AS. RESULTS: Among the 1,250 Belgian patients studied, disease duration was associated with risk of developing inflammatory bowel disease (IBD), with an increase in risk by 20% per 10 years of disease duration (relative risk [RR] 1.2, P = 0.026), and associated with risk of developing acute anterior uveitis, with an increase in risk by 30% per 10 years of disease duration (RR 1.3, P < 0.001). In the subgroup of 171 newly diagnosed patients with prospective follow-up data, higher mean C-reactive protein levels over time were demonstrated in those with acute anterior uveitis or IBD compared to those without EAMs or those with psoriasis alone (each P = 0.01). CONCLUSION: The risk of developing acute anterior uveitis or IBD, but not psoriasis, in patients with axial SpA seems to increase with disease duration and appears to be linked to a higher cumulative exposure to inflammation, thus providing a possible explanation for the differential structural progression observed in those with axial SpA.

Dual energy x-ray absorptiometry-based assessment of male patients using standardized bone density values and a national reference database.

Dual energy X-ray absorptiometry (DXA) measurements from different manufacturers provide different bone mineral density (BMD) values and derived T-scores and Z-scores. These differences result partly from technical differences in the algorithms for the determination of bone mineral content and bone area and partly from the use of different manufacturer-derived reference databases. The present study was to implement a uniform expression of BMD in all male patients by using standardized BMD (sBMD) values and referring to a newly established national male reference sample. In 8 bone densitometry centers throughout Belgium 229 young healthy men were measured on Hologic (Bedford, MA) or GE-Lunar (Madison, WI) bone densitometers. Quality control procedures were implemented and site cross-calibration performed using the European Spine Phantom. Absolute BMD values were converted to standardized values by validated formulas (sBMD). Clinically acceptable between-center differences were noted. No discrepancy was observed in terms of mean sBMD and standard deviations at the lumbar spine and proximal femur between the Belgian and the US reference populations. Region-specific sBMD thresholds for the diagnosis of male osteoporosis were calculated. The current data provide a basis to implement a nation-wide, uniform expression of BMD in male patients and allow harmonization of the BMD-based diagnosis and treatment of osteoporosis in men.

Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial.

INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. RESULTS: We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. CONCLUSION: In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. TRIAL REGISTRATION: EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.