Faculty Bibliography

OBJECTIVE: To compare categories for activity/severity according to the Disease Activity Score 28-joint count (DAS28), the Clinical Disease Activity Index (CDAI), and the Routine Assessment of Patient Index Data 3 (RAPID3), an index without formal joint counts calculated in 5 versus >100 seconds, as well as the European League Against Rheumatism (EULAR)- DAS28 and the RAPID3 response criteria, in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID 1) clinical trial of certolizumab pegol (CZP). METHODS: Post hoc analyses were performed using correlations, cross-tabulations, and kappa statistics. Patients (treated with CZP plus methotrexate [MTX] or placebo plus MTX) were classified at baseline and at 52 weeks as high, moderate, low activity/severity or remission, according to the DAS28 (>5.1, >3.2 to </=5.1, 2.6 to </=3.2, <2.6 [total range 0-10]), the CDAI (>22, >10 to </=22, >2.8 to </=10, </=2.8 [total range 0-76]), and RAPID3 (>12, >6 to </=12, >3 to </=6, </=3 [total range 0-30]), as well as for good, moderate, and poor EULAR-DAS28 and proposed RAPID3 response criteria. RESULTS: All measures were correlated significantly: RAPID3 with DAS28 and CDAI (rho > 0.7), higher than erythrocyte sedimentation rate with C-reactive protein level (rho = 0.47). At 52 weeks, DAS28, CDAI, and RAPID3 low activity/remission was seen in 30%, 44%, and 42% of CZP-treated patients versus 3%, 7%, and 10% of control patients. Good, moderate, and poor EULAR-DAS28 responses were seen in 30%, 51%, and 19% of CZP-treated patients versus 3%, 28%, and 70% of control patients, and for RAPID3 in 39%, 30%, and 32% of CZP-treated patients versus 8%, 16%, and 76% of control patients. Kappa and weighted kappa values ranged from 0.36-0.53, indicating fair to moderate agreement. CONCLUSION: RAPID3, DAS28, and CDAI give similar results to distinguish CZP patients from controls in the RAPID 1 clinical trial. DAS28 is specific for clinical trials; RAPID3 appears pragmatically useful for usual care

OBJECTIVES: Current aim of rheumatoid arthritis (RA) reatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with >/=10 years of disease were assessed. METHODS: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of </=2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with >/=10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). CONCLUSIONS: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course

OBJECTIVE: Data suggest that the use of disease control groups and proper use of power calculations were neglected in published reports. We surveyed these and other methodological shortcomings in reports published within the last decade about one specific topic, Behcet's syndrome. We reason that recognizing such methodological shortcomings will lead to better quality clinical and basic science articles. METHODS: Articles published in the 15 highest impact factor journals on rheumatology, ophthalmology, dermatology, and general medicine between January 1999 and January 2009 were searched for original reports on Behcet's syndrome. Study designs (study types and time element), control groups, demographic data, use of power calculations, and reporting of negative results were specifically tabulated. RESULTS: Most studies on Behcet's syndrome were cross-sectional (83%). Prospective longitudinal studies were few (7%). In a considerable proportion of papers (21%), some basic demographic data were missing. Power calculations were rare (3%) even in randomized controlled trials and were not considered at all in clinical hypothesis-testing. Disease control groups were present in slightly over half of clinical and laboratory original research, while just 13% of genetic association studies included disease controls. Only 12% of all reports concerned mainly negative outcomes. CONCLUSION: A considerable number of the published research articles have methodological weaknesses. The generalizability of what we observed in Behcet's syndrome to other research topics needs to be formally studied

Three major advances over the last decade have impacted the way we treat rheumatoid arthritis; early and aggressive treatment, use of disease activity measures leading to treat to target, and availability of biologic agents. No oral biologic agents are available at this time but promising data is emerging for two drugs, tofacitinib and fostamatinib, inhibitors of JAK and Syk kinases, respectively. This paper will review some of the relevant published data for these agents and discuss where they may be placed in our treatment options for RA