OBJECTIVES: Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0-100 mm visual analogue scale and time to first new flare.METHODS: Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)).RESULTS: 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference,-10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56%(HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2%(canakinumab) and 52.8%(TA) and serious adverse events were reported in 8.0%(canakinumab) and 3.5%(TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count.CONCLUSION: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

OBJECTIVE: To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA).METHODS: In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed.RESULTS: MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p<0.001) and ACR50 (22% vs 10%, p<0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p<0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28)(p<0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score)(p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score)(p<0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%).CONCLUSION: Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms.ClinicalTrials.gov, numberNCT00650078.

OBJECTIVE: Traditional outcome measures in randomized controlled trials (RCT) include well-established response criteria as well as ACR EULAR responses using Disease Activity Score 44 (DAS44)/DAS28 to assess improvement; however, a measure to assess worsening of disease has yet to be developed. This special interest group (SIG) was established to develop an evidence-based, consensus-driven standard definition of "flare" in rheumatoid arthritis (RA). METHODS: At OMERACT 8, the need for a standardized definition of RA flare was recognized; interested individuals developed a proposal to form a SIG. A literature review was performed to identify publications and abstracts with flare definitions applied in RA, JIA, and lupus RCT as well as concerning patient perspectives on disease worsening. A SIG was held at OMERACT 9 with breakout sessions for patients and investigators. RESULTS: The RA flare SIG was attended by about 120 participants, including 11 patients. Patients and investigators held separate breakout sessions to discuss various aspects of disease worsening. The following consensus was obtained at OMERACT 9: a working definition of flare should indicate worsening of disease activity (88%), persistence, and duration as critical elements (77%), and consideration of change or increase in therapy (74%). CONCLUSION: A working definition of RA flare was developed based on these votes: flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy; and a flare represents a cluster of symptoms of sufficient duration and intensity to require initiation, change, or increase in therapy. Using this working definition, evaluation of candidate domains will be conducted via Delphi exercise and further informed by patient focus groups. Validation of candidate definitions in appropriate RCT will be required.

OBJECTIVE: To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX). METHODS:/B> Patients receiving stable doses of MTX were randomized to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily [qd]) or matching placebo. The primary efficacy measure was the proportion of patients with >/= 20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, DAS/EULAR response, and individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing, and immunology assessments. RESULTS:/B> On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31-43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections. CONCLUSION: In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.