Obesity and the Risk of Incident Chronic Opioid Use in Rheumatoid Arthritis.

OBJECTIVE: The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). METHODS: Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. RESULTS: Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. CONCLUSION: Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.

Fibromyalgia 2016 criteria and assessments: comprehensive validation in a Norwegian population.

Background and aims The ACR1990 criteria of fibromyalgia (FM) have been criticized due to poor reliability of tender points counting (TPC), inconsistent definitions of the widespread pain, and by not considering other symptoms than pain in the FM phenotype. Therefore, several newer self-report measures for FM criteria have emerged. The aim of this study was to translate the fibromyalgia survey questionnaire (FSQ) to Norwegian and validate both the 2011 and the 2016 fibromyalgia survey diagnostic criteria (FSDC) against the ACR1990 criteria. Methods One hundred and twenty chronic pain patients formerly diagnosed with fibromyalgia according to the ACR1990 criteria, and 62 controls not diagnosed or where fibromyalgia was not suspected, were enrolled in this study. All responded to a Norwegian version of the FSQ. Also, they had a clinical examination according to ACR1990 fibromyalgia criteria including a counting of significant tender points with an algometer (TPC). The FSQ with the Widespread Pain Index (WPI) and Symptom Severity scale (SSS) subscales, Fibromyalgia Severity (FS) sum score, was examined for correlations with the fibromyalgia impact questionnaire (FIQ) and TPCs. Face-validity, internal consistence, test-retest reliability and construct validity with convergent and divergent approaches were examined and a Receiver Operating Characteristics (ROC) analysis was performed. Results The internal consistency of FS measured by Cronbach's alfa was good (=0.904). The test-retest reliability measures using intra class correlation were respectable for the FS, including WPI and SSS subscales (0.86, 0.84 and 0.87). FS, WPI and SSS correlated significantly with FIQ (0.74, 0.59 and 0.85) and TPC indicating an adequate construct, convergent validity. The medians of FS, WPI and SSS in the fibromyalgia-group were significantly different from the non-fibromyalgia-group indicating good construct, divergent validity. Using the 2011 and 2016 FSDC vs. ACR 1990 as a reference, sensitivity, specificity, positive likelihood ratio (LR +) and negative likelihood ratio (LR-) were identified. The accuracy rate for both 2011 and 2016 FSDC were respectable (84%). ROC analysis using FS revealed a very good Area Under the Curve (AUC) = 0.860. Conclusion The current study revealed that the Norwegian versions of FSQ is a valid tool for assessment of fibromyalgia according to the 2011 and 2016 (FSDC).

A comparison of direct and indirect methods for the estimation of health utilities from clinical outcomes.

BACKGROUND: Analysts frequently estimate health state utility values from other outcomes. Utility values like EQ-5D have characteristics that make standard statistical methods inappropriate. We have developed a bespoke, mixture model approach to directly estimate EQ-5D. An indirect method, "response mapping," first estimates the level on each of the 5 dimensions of the EQ-5D and then calculates the expected tariff score. These methods have never previously been compared. METHODS: We use a large observational database from patients with rheumatoid arthritis (N = 100,398). Direct estimation of UK EQ-5D scores as a function of the Health Assessment Questionnaire (HAQ), pain, and age was performed with a limited dependent variable mixture model. Indirect modeling was undertaken with a set of generalized ordered probit models with expected tariff scores calculated mathematically. Linear regression was reported for comparison purposes. Impact on cost-effectiveness was demonstrated with an existing model. RESULTS: The linear model fits poorly, particularly at the extremes of the distribution. The bespoke mixture model and the indirect approaches improve fit over the entire range of EQ-5D. Mean average error is 10% and 5% lower compared with the linear model, respectively. Root mean squared error is 3% and 2% lower. The mixture model demonstrates superior performance to the indirect method across almost the entire range of pain and HAQ. These lead to differences in cost-effectiveness of up to 20%. CONCLUSIONS: There are limited data from patients in the most severe HAQ health states. Modeling of EQ-5D from clinical measures is best performed directly using the bespoke mixture model. This substantially outperforms the indirect method in this example. Linear models are inappropriate, suffer from systematic bias, and generate values outside the feasible range.

Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.

BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Psychological factors such as depression and stress are under debate to contribute to the risk of relapse. The impact of mucosal healing to reduce the risk of relapse had not been studied prospectively. The aim of this study was to identify whether depression and stress increase and mucosal healing reduces the risk of clinical relapse in patients with UC in clinical remission. METHODS: Patients in clinical remission were followed prospectively for 1 year, or less if they relapsed. Endoscopy and histology score and long-term perceived stress (Perceived Stress Questionnaire) were measured at baseline. Mucosal healing was defined by a Mayo Endoscopy score of 0-1. Depression (Hospital Anxiety and Depression Scale) and acute perceived stress (Cohen Perceived Stress Scale) were measured at baseline and after 1, 3, 6, 9, and 12 months. A time-dependent multivariate Cox regression model determined the predictors of time to relapse. RESULTS: Seventy-five patients were included into final analysis, of which 28 (37.3%) relapsed. Short-term stress at the last visit before relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.10) and male gender (HR = 2.38, 95% CI = 1.01-5.61), but not baseline mucosal healing (HR = 0.86, 95% CI = 0.35-2.11), baseline long-term stress (HR = 0.20, 95% CI = 0.01-3.31), and depression at the last visit before relapse (HR = 1.08, 95% CI = 0.95-1.22) were predictive for a relapse. CONCLUSIONS: Short-term stress but not depression nor mucosal healing was predictive for the risk of relapse in patients with UC in clinical remission. Larger multicentre studies are necessary to confirm our findings.

The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis.

OBJECTIVE: This study aims to provide robust estimates of EQ-5D as a function of the HAQ and pain in patients with RA. METHOD: Repeated observations were made of patients diagnosed with RA in a US observational cohort (n = 100 398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We used a bespoke statistical method based on mixture modelling to appropriately reflect the characteristics of the EQ-5D instrument and to compare this with results from standard multiple regression. RESULTS: EQ-5D can be predicted from summary HAQ and pain scores. We identify four different classes of respondents who differ in terms of disease severity. Unlike the multiple regression, the mixture model exhibits very good fit to the data and does not suffer from problems of bias or predict values outside the feasible range. CONCLUSION: It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the quality-adjusted life year benefits, and therefore the cost-effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates. Reimbursement agencies rely on these types of analyses when formulating policy on the use of new drug therapies. Clinicians as well as economists should be concerned with these issues.

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis.

OBJECTIVES: The superiority of true drug treatment over placebo in reducing symptoms of fibromyalgia syndrome (FMS) is small and bought by relevant rates of drop-outs due to adverse events. Recent systematic reviews demonstrated that a substantial proportion of the beneficial and adverse effects of true drug is attributable to placebo in chronic pain trials. We determined the magnitude of the placebo and nocebo response and its impact on the benefits and harms of true drug in trials of drugs which were submitted for approval for treatment of FMS. METHODS: CENTRAL, MEDLINE and clinicaltrials.gov were searched from inception to June 30, 2012 for randomized double-blind placebo controlled trials with a parallel design for duloxetine, milnacipran, pregabalin and sodium oxybate in FMS-patients. The magnitude of placebo response was assessed by the pooled estimate of a 50% placebo pain reduction. The magnitude of nocebo response was determined by the pooled estimate of drop-out rates due to adverse events in placebo groups. RESULTS: 18 studies with 3546 patients on placebo were included. The pooled estimate of a 50% pain reduction by placebo was 18.6% (95% CI 17.4 to 19.9%). The pooled estimate of drop-out due to adverse events in placebo groups was 10.9% (95% CI 9.9 to 11.9%). CONCLUSIONS: The magnitude of placebo and nocebo response in trials of drugs applying for approval for FMS treatment was substantial. Study investigators aim to reduce placebo response. By contrast, clinicians often utilise placebo effects. Strategies to reduce nocebo responses in clinical trials and practice should be developed.

The 2010 American college of rheumatology fibromyalgia survey diagnostic criteria and symptom severity scale is a valid and reliable tool in a French speaking fibromyalgia cohort.

BACKGROUND: Fibromyalgia (FM) is a pain condition with associated symptoms contributing to distress. The Fibromyalgia Survey Diagnostic Criteria and Severity Scale (FSDC) is a patient-administered questionnaire assessing diagnosis and symptom severity. Locations of body pain measured by the Widespread Pain Index (WPI), and the Symptom Severity scale (SS) measuring fatigue, unrefreshing sleep, cognitive and somatic complaints provide a score (0-31), measuring a composite of polysymptomatic distress. The reliability and validity of the translated French version of the FSDC was evaluated. METHODS: The French FSDC was administered twice to 73 FM patients, and was correlated with measures of symptom status including: Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), McGill Pain Questionnaire (MPQ), and a visual analogue scale (VAS) for global severity and pain. Test-retest reliability, internal consistency, and construct validity were evaluated. RESULTS: Test-retest reliability was between .600 and .888 for the 25 single items of the FSDC, and .912 for the total FSDC, with all correlations significant (p < 0.0001). There was good internal consistency measured by Cronbach's alpha (.846 for FSDC assessment 1, and .867 for FSDC assessment 2). Construct validity showed significant correlations between the FSDC and FIQ 0.670, HAQ 0.413, MPQ 0.562, global VAS 0.591, and pain VAS 0.663 (all p<0.001). CONCLUSIONS: The French FSDC is a valid instrument in French FM patients with reliability and construct validity. It is easily completed, simple to score, and has the potential to become the standard for measurement of polysymptomatic distress in FM.

Pain as an important predictor of psychosocial health in patients with rheumatoid arthritis.

OBJECTIVE: To examine the evolution of psychosocial aspects of health-related quality of life in rheumatoid arthritis (RA) patients, and to identify their predictors. METHODS: All patients within a Swiss RA cohort and a US RA cohort who completed a Short Form 36 (SF-36) scale at least twice within a 4-year period were included. The primary outcome was psychosocial health as measured by the mental component summary (MCS) score of the SF-36. The evolution of this outcome over time was analyzed using structural equation models, which distinguish between the stable, the variable, and the measurement error components of the outcome's variance. RESULTS: A total of 15,282 patients (48,323 observations) were included. MCS scores were mostly stable over time (between 69% and 75% of the variance was not due to measurement error). The variable component of the SF-36 was mostly due to fluctuations at the moment of measurement and not to a global time trend of psychosocial health. Pain was the most important predictor of both the stable and variable components of psychosocial health, explaining ∼44% of the observed psychosocial health variance. CONCLUSION: This large cohort study demonstrates that pain is the most important predictor of a patient's psychosocial health in RA patients. This suggests that physicians should place greater emphasis on pain management.

Patient repositioning reproducibility of joint space width measurements on hand radiographs.

OBJECTIVE: Computer-based methods to measure radiographic joint space width (JSW) have the potential to improve the longitudinal assessment of rheumatoid arthritis (RA). The purpose of this report was to measure the long-term patient repositioning reproducibility of software-measured radiographic JSW. METHODS: Patients underwent baseline and followup hand radiography examinations with a followup time of ≤3 years. To eliminate any JSW change due to real disease progression, the evaluation was performed on "unaffected" joints, defined as having JSW and erosion Sharp scores of 0 at both baseline and followup. The root mean square SD (RMSSD) and coefficient of variation (CV) were used as the reproducibility metrics. RESULTS: The RMSSD was 0.14 mm (CV 10.5%) for all joints, 0.18 mm (CV 10.9%) for the metacarpophalangeal (MCP) joints, and 0.08 mm (CV 8.3%) for the proximal interphalangeal (PIP) joints. The distribution of JSW change was asymmetric, suggesting that narrowing due to RA progression occurred for several joints. A second analysis was performed, excluding joints where the loss of JSW was greater than 3 SDs. For this analysis, the RMSSD was 0.10 mm (CV 7.5%) for all joints, 0.12 mm (CV 7.3%) for the MCP joints, and 0.07 mm (CV 7.1%) for the PIP joints. CONCLUSION: Repositioning reproducibility is very good but is likely to be a dominating factor compared to reader and software reproducibility. Additionally, further evidence is given that a software method is able to detect changes in some joints for which the Sharp score is insensitive.

A comparison of patient characteristics and outcomes in selected European and U.S. rheumatoid arthritis registries.

PURPOSE: Randomized controlled trials (RCTs) have demonstrated the efficacy of biologic agents in the treatment of rheumatic diseases. However, results from RCTs may not be generalizable to clinical practice because of their strict inclusion and exclusion criteria. Assessment of safety using RCT data also is limited by short duration of follow-up and relatively small sample sizes, which generally preclude analysis of longer term outcomes and rare adverse events. In rheumatology, various observational cohorts and registries have been created to complement information obtained from RCTs, some with the primary purpose of monitoring effectiveness and safety of biologic agents. Most registries are either drug based or disease based. These registries include patients with a variety of rheumatic diseases including RA. METHODS: To provide a qualitative comparison of selected U.S. and European rheumatoid arthritis (RA) biologics registries and cohorts including ARTIS, BIOBADASER, BSRBR, BRASS, CLEAR, CORRONA, NDB, RABBIT, SCQM, and VARA. RESULTS: A careful comparison of these registries, as provided in this article, can provide a basis for understanding the many similarities and differences inherent in their design, as well as societal context and content, all of which can significantly impact their results and comparisons across registers. SUMMARY: The increasing use of biologic agents for treatment of rheumatic diseases has raised important questions about cost, safety, and effectiveness of these agents. The unique and variable features of patient populations and registry designs in Europe and the U.S. provide valuable and complementary data on comparative effectiveness and safety of biologic agents to what can be derived from RCTs.

Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT.

BACKGROUND: Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited. OBJECTIVE: To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function. RESULTS: Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant. CONCLUSIONS: Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.

Converting modified health assessment questionnaire (HAQ), multidimensional HAQ, and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients.

OBJECTIVE: The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ. METHODS: Analysis was limited to the comparison of rheumatoid arthritis (RA) patients at a random observation when the HAQ was recorded in conjunction with the MHAQ (n = 29,596), the MDHAQ (n = 13,665), or the HAQII (n = 15,823). Development models were randomly limited to 80% of the data (development sample) and the remaining 20% was used for model validation. RESULTS: Two conversion formulas were developed for each of the MHAQ, the MDHAQ, and the HAQII: a short model and a long model inclusive of questions common to both the modified measures and the original HAQ. Short models explained 81-83%, and long models 82-86%, of the variance. Predicted HAQ values of zero were assigned to all cases with an MDHAQ or HAQII score of zero, with remaining cases used for model estimation. Bland-Altman plots demonstrated good concordance between actual and predicted values for each measure. The validation sample closely approximated the results from the development sample (0.005 ≤ ΔR² ≤ 0.009) for each measure. CONCLUSION: We have developed and validated highly accurate conversion formulas from the MHAQ, MDHAQ, and HAQII to the original HAQ in a large sample of RA patients. The developed models are useful for conversion of measures in the research setting. Because of substantial variability at the individual patient level, application of the formulas to individual patients is inadvisable.

The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial.

OBJECTIVE: Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS: The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION: At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

Biologic drugs for rheumatoid arthritis in the Medicare program: a cost-effectiveness analysis.

OBJECTIVE: Since the introduction of the Medicare Prescription Drug Improvement and Modernization Act and its associated demonstration project, coverage of selected biologic drugs has been expanded for Medicare beneficiaries. For rheumatoid arthritis, coverage was extended to etanercept, adalimumab, and anakinra in addition to the previously covered infliximab. We undertook to develop a model to compare the costs and quality-adjusted life years (QALYs) generated by each of the 4 biologic agents. METHODS: Data were drawn from meta-analysis of randomized controlled trials and from a large longitudinal outcomes databank. Uncertainty was addressed using probabilistic and one-way sensitivity analyses. A lifetime horizon and Medicare viewpoint were adopted. RESULTS: In the base case analysis, anakinra was the least effective and least costly strategy. Etanercept, adalimumab, and infliximab were similar in terms of effectiveness, but infliximab was more costly. If decision makers are willing to pay a maximum of $50,000/QALY, the probability that infliximab is cost-effective is <1%. Findings were robust to a range of sensitivity analyses. Only if the dose of infliximab remains constant over time is this likely to be a cost-effective strategy. CONCLUSION: Infliximab is unlikely to be cost-effective in the Medicare population compared with either etanercept or adalimumab. Anakinra is substantially less costly but is also less effective than the 3 tumor necrosis factor alpha inhibitors.

Influence of nonclassical cardiovascular risk factors on the accuracy of predicting subclinical atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To determine whether nontraditional risk factors increase the accuracy of predicting the presence of carotid artery plaque based on traditional cardiovascular risk factors only in patients with rheumatoid arthritis (RA). METHODS: We identified risk factors that were independently associated with ultrasonographically located plaque. In predicting carotid artery plaque, the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for the combination of traditional and nontraditional risk factors was compared to the AUC of the ROC curve for traditional risk factors and nontraditional risk factors considered separately in 91 patients with RA. RESULTS: Thirty-one (34%) patients had carotid artery plaque. The 3 traditional risk factors of age > 55 years, hypertension, and ever-smoking, and the 3 nontraditional risk factors of a disease duration > 8 years, polymorphonuclear cell count > 4.5 x 10(6)/l, and hypothyroidism were each independently associated with the presence of plaque (odds ratios 2.08-8.78; p = 0.001-0.02). The percentage of patients with plaque was 0, 10%, 50%, and 83% in patients with 0-1, 2, 3, and 4-6 of these risk factors, respectively. In predicting plaque, the AUC of the ROC curve for the combination of traditional and nontraditional risk factors (0.90 +/- 0.03) was greater than that for either traditional (0.80 +/- 0.05; p = 0.006) or nontraditional (0.80 +/- 0.04; p = 0.005) risk factors considered separately. CONCLUSION: The combination of disease duration, polymorphonuclear cell counts, and thyroid status increased the accuracy of predicting subclinical atheroma in patients with RA. We believe that our findings merit external validation.

Minimal disease activity for rheumatoid arthritis: a preliminary definition.

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.