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ID PMID Title PublicationDate abstract
19426483 Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis. 2009 INTRODUCTION: Rheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA. METHODS: Synovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein. RESULTS: We observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay. CONCLUSIONS: Hypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA.
19725967 Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullina 2009 INTRODUCTION: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. METHODS: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. RESULTS: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. CONCLUSIONS: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.
20231197 Reproducibility of joint swelling assessment by sonography in patients with long-lasting r 2010 May OBJECTIVE: To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data. METHODS: In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen's kappa statistic. RESULTS: Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001). CONCLUSION: PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA.
19344530 Inflammation predicts accelerated brachial arterial wall changes in patients with recent-o 2009 INTRODUCTION: Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-mediated dilatation (GMD)) structural responses in early RA patients, and determined progress over one year. METHODS: Brachial artery FMD and GMD and carotid intima media thickness (cIMT) were studied using ultrasound in 20 patients diagnosed with early RA in whom symptoms had been present for less than 12 months, and in 20 control subjects matched for age, sex and established cardiovascular risk factors. FMD and GMD were re-assessed after 12 months in RA patients and the change in each parameter was calculated. Data were analysed by univariate regression. RESULTS: Mean FMD and GMD were significantly lower in early RA patients at baseline than in controls, but each parameter significantly improved in one year. FMD and GMD responses were positively associated with each other. Patients' age, C-reactive protein (CRP) level and cIMT at baseline and CRP level at one year, were negatively associated with change in brachial responses in one year. CONCLUSIONS: Patients with recent-onset RA have altered brachial artery responses signifying both functional and structural abnormalities. However, early control of inflammation may reduce arterial dysfunction and thus the tendency for atherosclerotic progression.
19644894 Depression, inflammation, and pain in patients with rheumatoid arthritis. 2009 Aug 15 OBJECTIVE: An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. METHODS: In total, 218 RA outpatients completed self-administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. RESULTS: Depression scores were mildly and positively correlated with the CRP level (r = 0.46, P < 0.001). Both the depression score (standardized beta = 0.35, P < 0.001) and the CRP level (standardized beta = 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. CONCLUSION: Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control.
20925993 Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. 2010 Jul Previous qualitative studies have revealed discrepancies between patients' and physicians' perceptions of rheumatoid arthritis (RA) and its treatment. Questionnaires were administered to 2795 patients with RA (756 from Europe; 2039 from the USA) to measure patients' perceptions regarding pain management in RA. Although the majority of patients reported their RA as somewhat-to-completely controlled, 75% of European and 82% of US patients reported their pain as moderate-to-severe in the previous 2 months. The majority of European (60%) and US (65%) patients reported dissatisfaction with their arthritis pain. Patients' pain levels corresponded with their disease severity. A higher percentage of patients who reported severe pain were being treated for depression than those who had moderate or mild pain. Patients in the USA rated pain relief as the top required benefit from their RA medication. A comprehensive examination of patients' perspectives regarding pain could lead to better patient care and pain management strategies.
19796371 Predicting joint damage in rheumatoid arthritis using MRI scanning. 2009 Predicting prognosis in the patient with newly diagnosed rheumatoid arthritis is of key importance so that high-cost therapies can be tailored to the needs of the individual. In a recent issue of Arthritis Research and Therapy, the prognostic significance of MRI changes at the forefoot has been studied. While progression to radiographic erosion occurred rarely in this group of patients exposed to potent disease-suppressing therapies, including TNF inhibitors, MRI bone edema, representing osteitis, has been further implicated as a forerunner to bone erosion. Early MRI scans of the forefoot were helpful in defining those with the potential to progress as well as those in a good prognosis category.
21046924 Autonomic (sympathetic) nervous system involvement in rheumatoid arthiritis patients. 2010 Jan Fifty Rheumatoid arthritis (RA) patients between the age group of 20 to 60 years were investigated for sympathetic autonomic functions using standard tests. All the patients liable to develop dysautonomia or having a treatment interfering with autonomic nervous system were excluded. Previous studies to evalute sympathetic nervous system involvement used only a single test like sweating response, orthostatic test. In the present study 3 tests of sympathetic nervous system evaluation have been used. The evaluation was done by cardiovascular tests like orthostatic test, sustained hand grip and cold pressor test. A control series of 50 healthy subjects was tested to determine abnormal threshold for each one of the 3 tests. The reference value of Ewing and Clark were used to interpret the results of the tests. Sympathetic dysfuction was found in 26% of rheumatoid arthritis patients.
20551094 Quantifying bone marrow edema in the rheumatoid cervical spine using magnetic resonance im 2010 Aug 1 OBJECTIVE: To determine the reliability and feasibility of a new magnetic resonance imaging (MRI) score to quantify bone marrow edema (BME), synovitis, and erosions in the cervical spine of patients with rheumatoid arthritis (RA); and to investigate the correlations among neck pain, clinical markers of RA disease activity, and MRI features of disease activity in the cervical spine. METHODS: Thirty patients with RA (50% with neck pain) and a Disease Activity Score 28-joint count > 3.2 had an MRI scan of their cervical spine. STIR, VIBE, and T1-weighted postcontrast sequences were used to quantify BME. MRI scans were scored for total BME, synovitis, and erosions using a new scoring method developed by the authors and assessed for reliability and feasibility. Associations between neck pain and clinical markers of disease activity were investigated. RESULTS: BME was present in 14/30 patients; 9/14 (64%) had atlantoaxial BME, 10/14 (71%) had subaxial BME, and 5/14 (36%) had both. Interobserver reliability for total cervical BME score was moderate [intraclass correlation coefficient (ICC) = 0.51]. ICC improved to 0.67 if only the vertebral bodies and dens were considered. There was no correlation between neck pain or clinical measures of RA disease activity and the presence of any MRI features including BME, synovitis, or erosions. CONCLUSION: Current RA disease activity scores do not identify activity in the cervical spine. An MRI score that quantifies BME, synovitis, and erosions in the cervical spine may provide useful information regarding inflammation and damage. This could alert clinicians to the presence of significant pathology and influence management.
19447930 Relationship between pack-year history of smoking and response to tumor necrosis factor an 2009 Jun OBJECTIVE: To determine whether there is a quantitative relationship between smoking history and response to therapy with tumor necrosis factor (TNF) antagonists. METHODS: A history of cigarette smoking was obtained from a questionnaire completed by each patient starting therapy with TNF antagonists since 2002 (n=154). A core set of demographic and clinical variables was recorded at baseline and at 3 and 12 months. The extent of smoking was quantified in pack-years (py), with 1 py equivalent to 20 cigarettes per day for 1 year. The association between smoking intensity and response was assessed using contingency tables and logistic regression analysis. Response to therapy was defined according to the European League Against Rheumatism improvement criteria. RESULTS: There was an increasing trend of no response at 3 and 12 months with increasing py history [p (trend)=0.008 and 0.003, respectively]. The change in Disease Activity Score (DAS)28 over the first 3 months was inversely associated with the number of py (r=-0.28, p=0.002). The association of py history with response failure was independent of age, sex, disease duration, baseline disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, IgM rheumatoid factor, and smoking at baseline. The most significant effect was seen in patients treated with infliximab. CONCLUSION: RA patients with a history of smoking were more likely to show a poor response to TNF antagonists. Response failure was associated with the intensity of previous smoking, irrespective of smoking status at initiation of anti-TNF therapy.
20049648 Immunotherapy of rheumatoid arthritis targeting inflammatory cytokines and autoreactive T 2010 Feb Rheumatoid arthritis is a chronic disorder for which there is no known cure. Concentrating on specific elements of the abnormal immune response that characterizes the disease, scientists are reaching into biotechnology's bag of tricks to develop immunotherapeutic techniques. This paper will present some advances in the immunotherapy of rheumatoid arthritis targeting inflammatory cytokines and autoreactive T cells.
21044442 Perioperative use of methotrexate. 2010 Sep Methotrexate (MTX) is the disease modifying antirheumatic 'anchor' drug for the treatment of patients with rheumatoid arthritis (RA). Despite its widespread use and the frequent need of elective orthopaedic and other types of surgical procedures in patients with RA, some confusion exists concerning the use of MTX in the perioperative period. Currently available data do not suggest a need to discontinue MTX because of surgery. There is some evidence that treatment with MTX is safe prior to and after elective surgical procedures. Importantly, disease activity is better controlled when MTX is not interrupted from weekly administration.
19333984 Physician ability to assess rheumatoid arthritis disease activity using an electronic medi 2009 Apr 15 OBJECTIVE: To assess physicians' concordance with Disease Activity Score in 28 joints (DAS28) categories calculated by an electronic medical record (EMR)-embedded disease activity calculator, as well as attitudes toward this application. METHODS: Fifteen rheumatologists used the EMR-embedded disease activity calculator to predict a rheumatoid arthritis (RA) DAS28 disease activity category at the time of each clinical encounter. RESULTS: Physician-predicted DAS28 disease activity categories ranged from high (>5.1, 15% of cohort, 66 of 429 patient visits) to moderate (>3.2-5.1, 21% of cohort, 90 of 429 patient visits) to low (2.6-3.2, 29% of cohort, 123 of 429 patient visits) to remission (<2.6, 35% of cohort, 150 of 429 patient visits). Overall concordance between calculated DAS28 results and physician-predicted RA disease activity was 64%. Using either the physician-predicted or the calculated DAS28 category as the gold standard, accuracy was greatest for patients in remission (75% and 88% accuracy, respectively) and those with high disease activity (68% and 79% accuracy, respectively), and less for patients with moderate (48% and 62% accuracy, respectively) or low disease activity (62% and 31% accuracy, respectively). CONCLUSION: Accurate physician prediction of DAS28 remission and high disease activity categories, even without immediate availability of the erythrocyte sedimentation rate or the C-reactive protein level at the time of the visit, may be used to guide quantitatively driven outpatient RA management.
20688805 Four different patterns of fatigue in rheumatoid arthritis patients: results of a Q-sort s 2010 Nov OBJECTIVES: Many patients with RA complain about fatigue. Whereas qualitative studies have covered the meaning of fatigue for RA patients, it was still unknown whether subgroups of patients could be distinguished. This study aimed to describe different perspectives on the experience of fatigue. METHODS: Participants were 30 outpatients with established controlled RA of the Medical Spectrum Twente, with a mean fatigue severity score of 4.67 (visual analogue scale 0-10). They evaluated 57 statements about fatigue according to Q-methodology. Data were analysed with PCQ for Windows (Portland, OR, USA), using centroid factor analysis with varimax rotation (i.e. the participants but not the items of a scale are the variables). Factor scores of statements on the different dimensions were calculated to investigate which items are relevant when describing and distinguishing fatigue experiences. Demographic and clinical patient characteristics were collected to describe each of the dimensions that resulted from centroid factor analysis. RESULTS: After statistical and theoretical considerations, a four-factor structure of the data was obtained. Each factor represented a perspective on the experience of fatigue, shared by a certain group of patients. Physical, psychological and social patient characteristics seemed to be associated with those experiences. The factors were labelled as: 'Little impact of fatigue'; 'Good coping and bad sleep'; 'Search for balance'; and 'High distress'. CONCLUSIONS: Results indicated that fatigue experience is a complex phenomenon. Existing questionnaires to measure fatigue do not meet this complexity. Extensive research is warranted and new efforts to develop instruments that take into account all aspects of fatigue are indicated.
20110517 Equivalent responses to disease-modifying antirheumatic drugs initiated at any time during 2010 Mar OBJECTIVE: To evaluate responses by time to initiation of nonbiologic disease-modifying antirheumatic drugs (DMARD) in a DMARD-naive cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months, range 0.6-15.9). Subjects who started their first DMARD within 5 months of symptom onset were compared to subjects who started after 5 months. Disease Activity Scores (DAS-44) and total Sharp Score (TSS) progression rates were analyzed using Wilcoxon rank-sum and chi-square tests; multiple linear regression analysis adjusted for potential covariates. The slope of the least-squares regression line was calculated to estimate the annualized TSS progression rates. RESULTS: Of 233 RA patients, 76% were female and mean age was 50 (SD 13) years. At DMARD start, DAS-44 was similar in all subsets within the 0.6 to 15 months' duration between symptom onset and DMARD initiation. Erosion scores tended to be higher in those who started DMARD later, but Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were higher in those who started DMARD earlier. During the 2 years after DMARD initiation, improvements in HAQ-DI and DAS-44 were similar in the various duration subsets, with about 25% ever achieving DAS remission (DAS < 1.6). Radiographic progression tended to be numerically but not statistically more rapid in the earlier subsets. CONCLUSION: Following initiation of nonbiologic DMARD therapy at various times within 15 months of symptom onset, improvements of DAS-44, HAQ-DI, remission rate, and radiographic progression rate were similar, although higher baseline erosion scores were present in those with later initiation of DMARD.
20179980 A case of dermatomyositis with "liver disease associated with rheumatoid diseases" positiv 2010 Aug We reported a case of dermatomyositis (DM) with liver disturbance in a 50-year-old Japanese female. She presented with fever, muscle weakness, and typical DM rashes. On clinical and serological examinations, the liver impairment was initially diagnosed as probable autoimmune hepatitis, which was denied by a histological study despite positive anti-liver-kidney microsome-1 antibody. Finally, she was diagnosed as having DM with "liver disease associated with rheumatoid diseases", and treatment with oral prednisone (40 mg/day) achieved normalization of liver and muscle enzyme levels as well as improvement of symptoms associated with DM. Liver involvement in patients with polymyositis (PM)/DM has not been well described and is considered to be uncommon. Full clarification of the etiology of liver impairment with a histological examination in collagen diseases including PM/DM is useful to determine the proper dose of corticosteroids for the treatment of collagen diseases and their liver complications.
19116932 Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription co 2009 Jan OBJECTIVE: Synoviolin is an E3 ubiquitin ligase, and its overexpression is implicated in the pathogenesis of rheumatoid arthritis (RA). We reported previously that Ets binding site 1 (EBS-1) within the synoviolin promoter is crucial for the expression of synoviolin, and GA binding protein (GABP) binds to this site. This study was undertaken to elucidate the precise mechanisms of transcriptional regulation via EBS-1. METHODS: We performed purification and identification of complex components that bind to EBS-1 and inspected their contributions to the transcriptional regulation of synoviolin in rheumatoid synovial cells. We biochemically purified proteins that had EBS-1 binding activity and identified the proteins using liquid chromatography tandem mass spectrometry analysis. The identified proteins were verified to recruit and form the complex on EBS-1 using electrophoretic mobility shift assay and coimmunoprecipitation assay. Furthermore, their transcription activities were tested by reporter assays and RNA interference experiments. RESULTS: We identified interleukin enhancer binding factor 3 (ILF-3) as a novel factor in the complex. ILF-3 was demonstrated to activate the synoviolin promoter via association with GABPalpha in rheumatoid synovial cells. In addition, further activation was observed with ILF-2 and GABPbeta, previously reported interactants of ILF-3 and GABPalpha, respectively. Moreover, ILF-3-knockdown experiments showed reduced expression of the synoviolin gene. CONCLUSION: Our findings indicate that ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABPalpha in rheumatoid synovial cells. ILF-3 might be a target for RA treatment through its effect on IL-2 in T cells and synoviolin in rheumatoid synovial cells.
19116921 Different patterns of associations with anti-citrullinated protein antibody-positive and a 2009 Jan OBJECTIVE: To identify additional variants in the major histocompatibility complex (MHC) region that independently contribute to risk in 2 disease subsets of rheumatoid arthritis (RA) defined according to the presence or absence of antibodies to citrullinated protein antigens (ACPAs). METHODS: In a multistep analytical strategy using unmatched as well as matched analyses to adjust for HLA-DRB1 genotype, we analyzed 2,221 single-nucleotide polymorphisms (SNPs) spanning 10.7 Mb, from 6p22.2 to 6p21.31, across the MHC. For ACPA-positive RA, we analyzed samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) and the North American Rheumatoid Arthritis Consortium (NARAC) studies (totaling 1,255 cases and 1,719 controls). For ACPA-negative RA, we used samples from the EIRA study (640 cases and 670 controls). Plink and SAS statistical packages were used to conduct all statistical analyses. RESULTS: A total of 299 SNPs reached locus-wide significance (P<2.3x10(-5)) for ACPA-positive RA, whereas surprisingly, no SNPs reached this significance for ACPA-negative RA. For ACPA-positive RA, we adjusted for known DRB1 risk alleles and identified additional independent associations with SNPs near HLA-DPB1 (rs3117213; odds ratio 1.42 [95% confidence interval 1.17-1.73], Pcombined=0.0003 for the strongest association). CONCLUSION: There are distinct genetic patterns of MHC associations in the 2 disease subsets of RA defined according to ACPA status. HLA-DPB1 is an independent risk locus for ACPA-positive RA. We did not identify any associations with SNPs within the MHC for ACPA-negative RA.
20676650 MBD4 gene is associated with rheumatoid arthritis in Chinese patients in Taiwan. 2012 Jan This study examines whether or not MBD4 polymorphism is a marker for rheumatoid arthritis (RA) susceptibility or severity for Chinese patients in Taiwan. This study included 193 patients with RA, while 190 unrelated healthy individuals living in Central Taiwan served as controls. The relationship between MBD4 polymorphism and clinical manifestations of RA was evaluated. For the genotype and allelic frequency of MBD4-1057 polymorphism, there were no statistically significant differences between patients with RA and controls. There were significant differences in the distribution of MBD4-8666 polymorphism frequencies between patients with RA and controls [P = 0.013; P (corrected) (Pc) = 0.039]. There were also significant relationships in the distribution of MBD4-9229 polymorphism genotype between patients with RA and controls (P = 0.007; Pc = 0.021). However, we did not detect any associations for MBD4-1057, MBD4-8666 or MBD4-9229 with rheumatoid factor presence, extra-articular involvement or bone erosion in patients with RA. Results suggest that MBD4-8666 and MBD4-9229, but not MBD4-1057, gene polymorphisms are related to RA in Chinese patients in Taiwan.
20843902 The Hawthorne effect, sponsored trials, and the overestimation of treatment effectiveness. 2010 Nov OBJECTIVE: To determine if the results of rheumatoid arthritis (RA) clinical trials are upwardly biased by the Hawthorne effect. METHODS: We studied 264 patients with RA who completed a commercially sponsored 3-month, open-label, phase 4 trial of a US Food and Drug Administration approved RA treatment. We evaluated changes in the Health Assessment Questionnaire disability index (HAQ) and visual analog scales for pain, patient global, and fatigue during 3 periods: pretreatment in the trial, on treatment at the close of the trial, and by a trial-unrelated survey 8 months after the close of the trial, but while the patients were receiving the same treatment. RESULTS: The HAQ score (0-3) improved by 41.3% during the trial, but only by 16.5% when the endpoint was the post-trial result. Similar results for the other variables were patient global (0-10) 51.9% and 34.6%, pain (0-10) 51.7% and 39.7%, fatigue (0-10) 45.6% and 24.6%. Worsening between the trial end and the first survey assessment was HAQ 0.29 units, pain 0.8 units, patient global 0.8 units, and fatigue 1.1 units. CONCLUSION: Almost half the improvement noted in the clinical trial HAQ score disappeared on entry to a non-sponsored followup study, and from 23% to 44% of improvements in pain, patient global, and fatigue also disappeared. These changes can be attributed to the Hawthorne effect. Based on these data, we hypothesize that the absolute values of RA outcome variables in clinical trials are upwardly biased, and that the treatment effect is less than observed.