Faculty Bibliography

OBJECTIVE: It is important to evaluate how a randomized controlled trial (RCT) sample was assembled from the general patient population in order to determine whether a patient differs from those who participated in the trial in a meaningful way. The aim of this study is to assess the adequacy of reporting of the recruitment process of rheumatoid arthritis (RA) patients participating in RCTs with biologic agents. METHODS: We searched PubMed for all reports of RCTs involving etanercept, infliximab, adalimumab, golimumab, certolizumab, abatacept, tocilizumab, and rituximab in RA patients. Data recorded were eligibility fraction, enrollment fraction, recruitment fraction, and number of patients needed to be screened (NNS) in order to randomize 1 participant. RESULTS: Of the 66 trials included in the analysis, 23 (35%) reported the number of individuals assessed by investigators for eligibility, and 18 (27%) reported the number eligible for participation. Of the studies that reported quantitative recruitment information, the median eligibility fraction was 80.6% (interquartile range [IQR] 71.8-91.1%) and the median enrollment fraction was 100% (IQR 88.4-100%). The median NNS was found to be 1.28 (IQR 1.18-1.43). CONCLUSION: A substantial majority of RCTs conducted in RA patients with biologic agents did not provide sufficient information about the patient recruitment process, which makes assessments of external validity difficult. The rate of reporting of the recruitment process in this study was found to be lower as compared to similar studies conducted in different specialties.

ABSTRACT: OBJECTIVE: Behcet's is an idiopathic multi-organ syndrome, which may have onset during childhood. Vascular involvement is uncommon, with rarely reported coronary aneurysm formation. We present a case report of a teenager girl who developed recalcitrant life-threatening Behcet's vasculitis, involving both small and large venous and arterial systems including a giant coronary aneurysm. CASE REPORT: De-identified data were collected retrospectively in case report format. Although our sixteen year old female with Behcet's vasculitis had resolution of many arterial aneurysms, she had persistent venous thrombosis of large vessels, as well as persistent, giant arterial aneurysms requiring intra-arterial coiling of a lumbar artery and coronary bypass grafting despite intensive immunosuppression including glucocorticoids, cyclophosphamide, infliximab, methotrexate, azathioprine and intravenous immunoglobulin. CONCLUSIONS: Vascular manifestations may be seen in Behcet's syndrome, including asymptomatic coronary aneurysm, which may be refractory to immunosuppression and ultimately require surgical intervention. Increased awareness is essential for prompt diagnosis and management.

OBJECTIVES: The new 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been designed to classify early onset RA, but has not been studied to identify RA in patients with arthritis seen in routine clinical care where correct 'classification' of patients, when they are not selected for having RA would be important. DESIGN: Prospective, consecutive patients cohort. SETTING: Outpatient clinic of a university rheumatology centre. PARTICIPANTS: A total of 126 patients with joint symptoms were consecutively recruited. INTERVENTIONS: The ACR/EULAR RA criteria were applied, with questions followed by a targeted musculoskeletal exam. The gold standard for the diagnosis of RA was the primary rheumatologist's diagnosis. PRIMARY OUTCOME MEASURE: Number of patients with non-RA diagnosis who were classified as having RA by the new classification criteria. RESULTS: The sensitivity and specificity of the 2010 criteria in classifying RA were 97% and 55%, respectively, compared with the 1987 RA criteria which were 93% and 76%, respectively. The 2010 criteria as applied to this group of patients had a poorer positive predictive (44% vs 61%) and a similar negative predictive value (98% vs 97%) compared with the 1987 criteria. More specifically, 66.7% of systemic lupus erythematosus patients, 50% of osteoarthritis, 37.5% of psoriatic arthritis and 27.2% of others fulfilled the new criteria and could have been classified as RA. CONCLUSIONS: In this, we believe, the first study to examine the new 2010 ACR/EULAR RA criteria among consecutive patients seen in routine care, we found the criteria to have low specificity, and therefore incorrectly label those as having RA when, in fact, they may have a different type of inflammatory arthritis. Physicians need to be aware of this when applying the new criteria for classifying their patients for any purpose.

ABSTRACT: In the absence of head-to-head trials, analysis of available data from randomized clinical trials allows for comparison of the efficacy of biologic agents for the treatment of rheumatoid arthritis. Methotrexate (MTX) inadequate responder trials provide data suggesting no major differences among any of the biologic agents, which is also confirmed in MTX naive population trials, when available, possibly a more reliable comparison group. The decision to pick one over the other should focus on safety, long-term survival of the drug and ease of use, which is for the most part influenced by patient preferences.

OBJECTIVE: To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. METHODS: The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. RESULTS: The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. CONCLUSIONS: This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. Trial Registry no NCT00531817