Faculty Bibliography

OBJECTIVES:To assess the process related to each infusible biologic used in rheumatoid arthritis (RA) with regard to patient and physician engagement in the infusion process, ancillary services required, and participant preferences.METHODS:This was a cross-sectional survey of patients with RA and their physicians. Biologic-naive patients with RA starting abatacept, infliximab, or rituximab were included. Both patients and physicians completed detailed questionnaires related to the infusion and satisfaction with the process.RESULTS:A total of 205 patients were enrolled: abatacept (n=102), infliximab (n=74), rituximab (n=29). Patients were primarily female (75%), Caucasian (85%), with a mean age of 58 years. Patients had a mean disease duration of approximately 8 years and had typically failed multiple DMARDs. Rituximab required the most pre-infusion preparation and the longest infusion time. Abatacept was associated with a shorter mean infusion time (42 minutes) than infliximab (131 minutes; p<0.0001) or rituximab (274 minutes; p<0.0001) and required less time away from work/home (p=0.01 and p<0.0001, respectively). Abatacept patients reported significantly less discomfort than rituximab patients (p=0.03), while discomfort was similar between abatacept and infliximab. From the physicians' perspective, compared to infliximab and rituximab abatacept was very easy to administer (57% vs. 27% and 5%, respectively), caused no pain/discomfort (52% vs. 42% and 31%), and had very infrequent infusion reactions (75% vs. 30% and 44%).CONCLUSION:The process involved in infusion administration, as perceived by both the patient and physician, seems to differ across the three infusible biologic agents and may have an impact on the decision-making process regarding which infusible biologic to use

OBJECTIVE: To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. METHODS: We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). CONCLUSION: MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

OBJECTIVE: Studies have suggested that early institution of tumor necrosis factor (TNF) inhibitors improves functional status and slows radiographic progression among patients with rheumatoid arthritis (RA). To determine whether these findings have altered practice patterns, we used the Consortium of Rheumatology Researchers of North America (CORRONA) registry to assess the pattern of TNF inhibitor utilization in the US over time. METHODS: Demographics and disease activity data were collected for patients with RA. The trend of TNF inhibitor use during 2002-06 was evaluated prospectively using linear and logistic regression models. RESULTS: Of the 11,397 patients with RA, 66% and 34% had established RA and early RA (disease duration < 3 yrs), respectively. The majority of patients were female and Caucasian. Despite comparable levels of disease activity, more of the patients with established RA were taking TNF inhibitors than those with early RA (40% vs 25%; p < 0.0001). The majority of patients (70%) taking TNF inhibitors were also receiving disease modifying antirheumatic drugs. The use of TNF inhibitors increased at a rate of 2.8% per year in established RA and 1.2% per year in early RA. The mean Clinical Disease Activity Index at the start of TNF inhibitors decreased at a rate of -0.233 per quarter (p = 0.006), while the mean Disease Activity Score decreased at a rate of -0.04 per quarter (p = 0.022). CONCLUSION: Utilization of TNF inhibitors in this multicenter, observational US cohort is increasing in both early and established RA, although it is more prominent among patients with established RA. The level of disease activity at which TNF inhibitors were initiated decreased over time in patients with both established and early RA.

OBJECTIVE: Patients with rheumatoid arthritis (RA) commonly switch between tumor necrosis factor (TNF) inhibitors after failing to control disease activity. Much of the clinical data that support switching to a second TNF agent when one agent fails to work has come from small, short-term studies. We utilized a US insurance claims database to determine patterns of use such as dose escalation, time to discontinuation, and switching between TNF inhibitors in patients with RA. METHODS: A retrospective analysis was performed using an insurance claims database in the US from 2000 to 2005. TNF inhibitor use, time to switch, dose escalation, and continuation times were analyzed in patients with RA. RESULTS: Nine thousand seventy-four patients with RA started TNF inhibitors during the period 2000 to 2005. Etanercept was the most commonly used TNF inhibitor; infliximab had the highest duration of continuation, about 50% at 2 years. In addition, infliximab showed higher rates of dose escalation compared to etanercept and adalimumab. For all TNF inhibitors, time to switching decreased from 2000 to 2005. CONCLUSION: TNF inhibitor use patterns changed from 2000 to 2005, with more frequent changes among the different TNF inhibitors and a shorter duration of treatment before the change. Only about 50% of TNF inhibitors are still continued at 2 years, reflecting the difference between randomized clinical trials and real-world experience

BACKGROUND:Cardiovascular disease (CVD) is a major cause of increased mortality in rheumatoid arthritis (RA) patients, and it is recommended to treat risk factors for CVD in RA patients aggressively, including increased lipid levels. However, the effect of biological disease modifying antirheumatic drugs (DMARD) on the lipid profile of RA patients remains under-researched, and what data exist are often contradictory. OBJECTIVES:To review available data published to date on lipid profile changes in RA patients treated with biologic DMARDs.METHODS:We searched the PubMed database without time limits until January 31, 2008 for original clinical trials regarding the effect of biological DMARDs on the lipid profiles of RA patients, tabulating total cholesterol, LDL, HDL and atherogenic index (ratio of total cholesterol to HDL) data for RA patients treated with biologic DMARDs. Percent change values from baseline to end of study were calculated.RESULTS:Eighteen studies fulfilled our inclusion criteria. The total cholesterol levels of patients treated with biological DMARDs was reported to increase in eleven studies (mean change 14.8%). One study reported a decrease (change 4.07%), and six reported no significant change. In HDL levels, nine studies reported increases (mean change 13.1%), two reported decreases (mean change 8.69%) and six reported no significant changes. Five studies reported an increase in LDL levels (mean change 11.2%), no studies reported a decrease, and six studies reported no significant change. The atherogenic index was reported to increase in two studies (mean change 4.27%), decrease in two studies (mean change 7.26%), and not significantly change in nine studies. Only a third of the reviewed articles reported on the LDL/HDL ratio, but of those that did, two reported an increase (mean change 4.55%), one reported a decrease (change 8.03%), and three reported no significant changes.DISCUSSION:Our data suggest increases in lipid levels between baseline and end of study in clinical trials of RA patients treated with biologic DMARDs. However, the clinical implications of this finding with regard to cardiovascular outcomes are not clear in part due to the fact that in most of the studies the atherogenic index was not significantly changed from baseline to end of study. Those studies that do provide data on effects on cholesterol rarely provide information on the complete lipid profile

OBJECTIVE:To examine effects of the COX-2 inhibitor market withdrawals on NSAID utilization among patients at increased risk of gastrointestinal (GI) and cardiovascular (CV) toxicities. METHODS:A prospective cohort study was conducted using patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. The study population included rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients prescribed NSAIDs by rheumatologists from 1/1/2003 to 12/31/2005. Three cohorts were defined based on calendar year. The primary outcome assessed whether or not an NSAID gastroprotective strategy was prescribed. Secondary outcomes included rates of COX-2 inhibitor utilization and gastroprotective co-therapy utilization, stratified by the presence of cardiac and GI risk factors. RESULTS:NSAID gastroprotection utilization decreased from 65.1% in 2003 to 47.7% (p<0.001) in 2005. COX-2 inhibitor use decreased from 55.1% to 29.2% (p<0.001), whereas nonselective NSAIDs (nsNSAIDs) use increased from 50.2% to 73.9% (p=<0.01). Among patients with two or more risk factors for NSAID related GI bleeding, gastroprotection decreased from 74.4% in 2003 to 60.9% (p<0.01). For patients with two or more CV risk factors from 2003 to 2005, COX-2 inhibitor utilization decreased significantly, whereas nsNSAID utilization increased significantly.CONCLUSIONS:The COX-2 inhibitor withdrawals resulted in a rapid decline in NSAID gastroprotection prescribed by participating U.S. rheumatologists despite the availability of other gastroprotective options. Channeling toward nsNSAID use was widespread, including among patients at increased CV risk. Longer term follow-up is required to determine the clinical significance of these changes in NSAID prescribing, particularly for NSAID-related GI and CV-related toxicities

ABSTRACT: INTRODUCTION: Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS: The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS: Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS: In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself