Rheumatoid Arthritis: Felson DT

Felson DT. · No affiliation provided · Arthritis Res Ther. · Pubmed #18341701 links to  free full text

Abstract: Geographic or ethnic differences in the occurrence of disease often provide insights into causes of disease and possible opportunities for disease prevention. Persons in China appear to have a consistently lower prevalence of rheumatoid arthritis and fibromyalgia than persons in the United States and Europe; reasons for these prevalence differences might include genetic differences, differences in environmental exposures or a combination of both. With increasing obesity, gout is becoming endemic in China. Finally, symptomatic knee osteoarthritis is extremely common in China and constitutes a major public health problem there.

Neogi T, Felson DT. · No affiliation provided · J Rheumatol. · Pubmed #18260160 links to  free full text

This publication has no abstract.

Felson DT. · No affiliation provided · J Rheumatol. · Pubmed #15124237 links to  free full text

This publication has no abstract.

van Tuyl LH, Vlad SC, Felson DT, Wells G, Boers M. · VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #19405006 No free full text.

Abstract: OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

Oldfield V, Felson DT. · Wolters Kluwer Health|Adis, Auckland, New Zealand. · Curr Opin Rheumatol. · Pubmed #18388530 No free full text.

This publication has no abstract.

Boers M, Anderson JJ, Felson DT. · VU University Medical Centre, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #12734919 No free full text.

Abstract: This article summarizes the process proposed to come to a definition of low disease activity in rheumatoid arthritis (RA). The purpose of this definition is to aid the interpretation of trial and longitudinal study results. A conceptual proposal is "a disease activity state that is deemed a useful treatment target by both physicians and patients." An operant definition can be derived by judgmental (opinion-based) or statistical (data-based) approaches, but the first seems more appropriate. Once a few candidate definitions have been selected, their usefulness and prognostic validity can be tested in longitudinal datasets.

Felson DT, Anderson JJ. · Boston University Arthritis Center, Massachusetts, USA. · J Rheumatol. · Pubmed #11246690 No free full text.

Abstract: We have assessed the discriminant validity of functional status measures and measures that are part of the core set for rheumatoid arthritis. Papers were identified by a systematic literature search in MEDLINE and hand searching of references.

Felson DT, LaValley MP, Baldassare AR, Block JA, Caldwell JR, Cannon GW, Deal C, Evans S, Fleischmann R, Gendreau RM, Harris ER, Matteson EL, Roth SH, Schumacher HR, Weisman MH, Furst DE. · Boston University School of Medicine, Massachusetts, USA. · Arthritis Rheum. · Pubmed #10524687 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

van Gestel AM, Anderson JJ, van Riel PL, Boers M, Haagsma CJ, Rich B, Wells G, Lange ML, Felson DT. · Department of Rheumatology, University Hospital Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #10090187 No free full text.

Abstract: We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.

Zhang B, Lavalley M, Felson DT. · Clinical Epidemiology Unit, Boston University, 715 Albany Street, A203 Boston, MA 02118, USA. · Ann Rheum Dis. · Pubmed #18697778 No free full text.

Abstract: OBJECTIVE: To test whether rheumatoid arthritis (RA) trials treatment efficacy versus control is better detected for patients with lower tender joint counts (TJC) or swollen joint counts (SJC) than for higher counts. METHODS: Using data from six large multicentre trials (N = 2002) and an intent-to-treat approach at 6 months, two subtrials were created within each trial, the lower disease activity group (defined by TJC less than overall median) and the higher disease activity group. The same approach was used for SJC. Active treatment was tested for treatment control differences using several RA trial outcome measures: ACR20, EULAR response, ACRHybrid. Sample sizes needed for higher TJC and SJC RA trials versus lower TJC and SJC trials were compared. RESULTS: Subtrials of subjects with lower TJC were found to have much higher sensitivity to change than those of subjects with higher TJC across all trials and outcome measures. A trial with lower TJC patients would require a smaller sample size than those with higher TJC patients. Results were not consistent for SJC subgroups. Three reasons were found for sensitivity to change of lower TJC: compared with higher TJC, those with lower TJC showed greater response to active treatment. SUBJECTS: with higher TJC on control treatment had greater percentage improvement and more variable responses than those in the lower TJC group. CONCLUSIONS: In RA trials, patients with lower disease activity within the range of current trial eligibility are more likely to show treatment efficacy than patients with higher disease activity. Lowering thresholds especially for TJC in trials may make it easier to detect treatment effects in RA.

Neogi T, Xie H, Felson DT. · Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts 02118, USA. · J Rheumatol. · Pubmed #18412313 No free full text.

Abstract: OBJECTIVE: We assessed whether individual American College of Rheumatology core set measures (CSM), and the CSM grouped as composite patient-derived (CPD) or composite physician/assessor-derived (CMD), performed differently in rheumatoid arthritis (RA) clinical trials. METHODS: We used data from 9 RA trials [anti-tumor necrosis factor-alpha (TNF-alpha) and disease modifying antirheumatic drug (DMARD)] in which CSM had been assessed, conducted from the early 1990s to present, with a total of 2969 patients. We grouped the CSM as CPD (pain, patient global assessment, function) and CMD [tender joint count (TJC), swollen joint count (SJC), physician global, inflammatory marker]. Using bootstrap simulation, we estimated the sample size that would be required to distinguish active treatment from placebo with the Wilcoxon rank-sum test in the clinical trials for the outcomes of percentage change of each individual CSM, of the Disease Activity Score (DAS), and average percentage change of the CMD or of the CPD. RESULTS: Comparing the performance of individual CSM relative to one another, the physician and patient global assessments and TJC would require the lowest sample sizes to distinguish active treatment from placebo, while use of the SJC, inflammatory marker, and function would require the highest. The CMD performed similarly to the DAS, requiring similar sample sizes, while the CPD would require 1.7 times greater sample size to distinguish treatment from placebo. The results were similar across DMARD and anti-TNF-alpha trials. CONCLUSION: Because of their demonstrated sensitivity to change, composite measures assessing RA outcomes in clinical trials should continue to include physician/assessor-derived core set measure assessments.

Felson DT, Zhang B, Siegel JN. · Clinical Epidemiology Unit, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA. · Ann Rheum Dis. · Pubmed #18408109 No free full text.

This publication has no abstract.

Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH, Anonymous00077. · CDC, Atlanta, Georgia 30341-3717, USA. · Arthritis Rheum. · Pubmed #18163481 links to  free full text

Abstract: OBJECTIVE: To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by arthritis overall, rheumatoid arthritis, juvenile arthritis, the spondylarthritides, systemic lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. A companion article (part II) addresses additional conditions. METHODS: The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey (NHIS). For analysis of overall arthritis, we used the NHIS. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. RESULTS: More than 21% of US adults (46.4 million persons) were found to have self-reported doctor-diagnosed arthritis. We estimated that rheumatoid arthritis affects 1.3 million adults (down from the estimate of 2.1 million for 1995), juvenile arthritis affects 294,000 children, spondylarthritides affect from 0.6 million to 2.4 million adults, systemic lupus erythematosus affects from 161,000 to 322,000 adults, systemic sclerosis affects 49,000 adults, and primary Sjögren's syndrome affects from 0.4 million to 3.1 million adults. CONCLUSION: Arthritis and other rheumatic conditions continue to be a large and growing public health problem. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions, more studies generalizable to the US or addressing understudied populations are needed.

Felson DT, Furst DE, Boers M. · Boston University School of Medicine, Boston, Massachusetts 02118, USA. · J Rheumatol. · Pubmed #17477484 No free full text.

Abstract: OBJECTIVE: To assess whether the American College of Rheumatology response criteria ACR20 should be replaced by another definition of response with enhanced discriminant validity. METHODS: We worked with statisticians to define over 100 different ways of defining response, including dichotomous definitions (e.g., ACR20; ACR50; ACR70; low disease activity), ordinal definitions (EULAR response; ACR20, ACR50, ACR70), disease activity indexes [Disease Activity Score (DAS); Disease Activity Index, SDAI], continuous definitions (mean percentage improvement in all core set measures; nACR, ACRn), and hybrid definitions (ACR20, ACR50, ACR70 defined for a patient as 0, 1, 2, 3 scale with continuous measures between intervals) along with variations on each of these approaches (e.g., percentage vs absolute change in DAS; e.g., measures requiring vs not requiring joint count improvement). To test clinical validity, we administered a survey using patients from a trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. For Sn-to-Chge, we are collecting data from large disease modifying antirheumatic drug multicenter trials in rheumatoid arthritis and ranking candidate definitions of response on their average p values in distinguishing active treatment from placebo or combination compared to single comparator. RESULTS: We surveyed 52 rheumatologists about which trial patients had improved and by how much. Trial data were obtained and tested for sensitivity to change. CONCLUSION: A rigorous data-driven consensus process was used to reassess the ACR20.

Wells GA, Boers M, Shea B, Brooks PM, Simon LS, Strand CV, Aletaha D, Anderson JJ, Bombardier C, Dougados M, Emery P, Felson DT, Fransen J, Furst DE, Hazes JM, Johnson KR, Kirwan JR, Landewé RB, Lassere MN, Michaud K, Suarez-Almazor M, Silman AJ, Smolen JS, Van der Heijde DM, van Riel PL, Wolfe F, Tugwell PS. · Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #16206362 No free full text.

Abstract: Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.

Fraenkel L, Bogardus ST, Concato J, Felson DT, Wittink DR. · VA Connecticut Healthcare System, West Haven, CT 06516, USA. · Ann Rheum Dis. · Pubmed #15020312 links to  free full text

Abstract: OBJECTIVE: To elicit treatment preferences of patients with rheumatoid arthritis (RA) for disease modifying antirheumatic drugs (DMARDs) with varying risk profiles. METHODS: Patient values for 16 DMARD characteristics were ascertained using published data about side effects, effectiveness, and cost. Patient preferences were determined by Adaptive Conjoint Analysis, an interactive computer program that predicts preferences by asking patients to make trade-offs between specific treatment characteristics. Simulations were run to derive preferences for four drugs: methotrexate, gold, leflunomide, and etanercept, under different risk-benefit scenarios. Infliximab was not included because it is given with methotrexate, and we did not include preferences for combination therapy. Based on each patient's expressed preferences, and the characteristics of the treatments available at the time of the study, the option that best fitted each patient's perspective was identified. RESULTS: 120 patients (mean age 70 years) were interviewed. For the base case scenario (which assumed the maximum benefits reported in the literature, a low probability of adverse effects, and low equal monthly "co-pays" (out of pocket costs)), 95% of the respondents preferred etanercept over the other treatment options. When all four options were described as being equally effective, 88% continued to prefer etanercept owing to its safer short term adverse effect profile. Increasing etanercept's co-pay to $30.00 decreased the percentage of patients preferring this option to 80%. CONCLUSIONS: In this study, older patients with RA, when asked to consider trade-offs between specific risk and benefits, preferred etanercept over other treatment options. Preference for etanercept is explained by older patients' risk aversion for drug toxicity.

Anderson JJ, Bolognese JA, Felson DT. · Boston University, Boston, Massachusetts 02118, USA. · Arthritis Rheum. · Pubmed #14613263 links to  free full text

Abstract: OBJECTIVE: Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. METHODS: We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. RESULTS: The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. CONCLUSION: The simulation studies demonstrate that data-driven outcome definitions can provide better sensitivity to change than does the ACR20 or DDAS. Using such methods would improve power, but at the expense of trial standardization. The studies also show how patient population and treatment characteristics affect the power of specific outcome measures in RA clinical trials, and provide quantification of those effects.

Anderson JJ, Wells G, Verhoeven AC, Felson DT. · Boston University School of Medicine, Massachusetts, USA. · Arthritis Rheum. · Pubmed #10643696 links to  free full text

Abstract: OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.

Lipsky PE, Felson DT, Maini RN. · No affiliation provided · Arthritis Rheum. · Pubmed #12384946 links to  free full text

This publication has no abstract.