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ID PMID Title PublicationDate abstract
10503562 Decreased peripheral blood T cell cytokine gene expression in rheumatoid arthritis. 1999 Currently, few informations are available about spontaneous production of T cell cytokines in rheumatoid arthritis (RA) peripheral blood (PB), because these cytokines are generally under the detection threshold of ELISAs. Because the Th1/Th2 balance could help to determine the outcome of RA, we used a sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to mesure spontaneous T cell production of IL-2, IL-4, IL-10, and IFN-gamma mRNAs using unstimulated PBMC from 25 active RA patients, not taking any DMARDs for at least 6 weeks, and 19 healthy controls. Spontaneous IL-2 and IL-4 mRNA expressions are significantly lower in RA patients compared to healthy controls. Levels of IL-10 and IFN-gamma are similar in the two groups. No correlation was found between cytokine mRNA levels and clinical parameters. Spontaneous IL-4 and IL-10 mRNA levels are respectively correlated to the number of CD4+ T cells and to the number of monocytes in PB. After in vitro stimulation, IFN-gamma mRNA production by RA PBMC is significantly decreased. Most of the patients cannot be classified as having a T cell cytokine type 1 or type 2 secretion pattern in PB. IL-2 and IL-4 mRNAs in PB of active RA are produced at a low spontaneous level and the response to in vitro activation by mitogen is weak.
11577402 [Clinical study on mortality of rheumatoid arthritis compared with malignant rheumatoid ar 2001 Aug OBJECTIVE: To determine how the mortality of patients with rheumatoid arthritis (RA) behave in comparison with that of patients with malignant rheumatoid arthritis (MRA). METHODS: The mortality of RA patients selected at randam identified in 1991-2000 (n = 104) was compared with that of 18 MRA patients. Hazard ratios of death were calculated with a multivariate survival analysis. A clinical study of patients with both RA and MRA was performed in mortality. RESULTS: Excess mortality was seen in MRA patients in Kaplan-Meier survival curves (p = 0.02 by log-rank test). MRA patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in both RA and MRA patients. Vasculitis was not reported as the cause of death in MRA patients. Secondary amyloidosis played an important role in RA death rather than MRA. CONCLUSION: There remained an excess mortality in MRA patients compared with RA, and infection was attributable to the key cause of death in both RA and MRA suggesting therapeutic side effects.
11393506 Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept. 2001 Jun Patients with long-standing, severe, erosive rheumatoid arthritis who have extra-articular manifestations and have undergone joint replacement surgery are at increased risk for serious infection and premature mortality. New therapies, including cytokine antagonists, hold great promise for improving the course of rheumatoid arthritis. However, they have powerful anti-inflammatory effects that may mask symptoms of serious infection. We report a case of fatal pneumococcal sepsis occurring in a 37-year-old woman with rheumatoid arthritis treated with the tumor necrosis factor antagonist etanercept and suggest management strategies for early detection and management of this complication.
10777121 Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients wi 2000 CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.
9516666 Schizophrenia among patients treated for rheumatoid arthritis and appendicitis. 1998 Feb 9 The widely accepted negative association between schizophrenia and rheumatoid arthritis (RA) is based on the results of investigations which sought RA in large samples of schizophrenic patients. Using a discharge register, we examined the frequency of schizophrenia in a sample of 5626 RA patients. Appendicitis patients (n = 5330) were used as a comparison group. The cumulative incidence of hospital care with the diagnosis of schizophrenia during 8 years was higher in the RA group (0.64%) than in the appendicitis group (0.47%). Schizophrenia was significantly more common in the RA group than in the appendicitis group among the young. The age-adjusted prevalence of schizophrenia was 0.96% in the RA group and 0.51% in the appendicitis group. Because of this unexpected finding, we examined the incidence of RA and appendicitis among a birth cohort born in 1966. The frequencies of RA and appendicitis among schizophrenic cohort members (n = 76), cohort members with psychiatric diagnosis other than schizophrenia (n = 438), and members without psychiatric diagnosis (n = 10503) were similar. These findings do not support the negative association between schizophrenia and RA. Prolonged institutionalization per se may have been the protective factor against RA in the previous studies. The findings also raise the hypothesis that genes that predispose to schizophrenia provide protection from appendicitis, historically a common cause of mortality.
9189012 Polymorphism of the human immunoglobulin heavy chain locus in rheumatoid arthritis. 1997 The genetic origin of Rheumatoid Arthritis (RA) is largely unknown. The purpose of this investigation was to assess the potential genetically determined involvement of the immunoglobulin (Ig) heavy chain variable region (VH) locus in the pathogenesis of RA. We tested the hypothesis of whether there is a genetic linkage between a structural abnormality of the VH gene complex and autoantibody hyperproduction in RA. We used restriction endonuclease generated polymorphism with human VH gene-family-specific probes to examine genomic DNA from a RA family and from unrelated RA patients from both the Tunisian and the European populations. The use of DNA samples from these ethnic origins permitted a further evaluation of the polymorphism of the human VH locus. While we found that the polymorphism of the VH locus was lower in the Tunisian population, we could not detect a restriction site polymorphism pattern restricted to RA. Together, our results do not support the involvement of major abnormalities of the Ig VH locus as a primary source in the development of RA.
10036640 Tyrosine phosphorylated proteins in synovial cells of rheumatoid arthritis. 1998 Two of the key events in the pathogenesis of rheumatoid arthritis are the synovial cell proliferation and lymphocyte infiltration into the synovium. The resulting synovitis is longlasting and leads to destructive arthritis, which is a hallmark of rheumatoid arthritis. Accumulating evidence suggests that one of the key biochemical events in the altered cell function of RA is phosphorylation of the tyrosine residues of proteins. In this paper we review the cellular components participating in the chronic inflammation of RA joints. We present the results of analyzing tyrosine phosphorylated proteins of synovial cells from RA patients and discuss a possible pathogenic role of non-receptor tyrosine kinase in RA.
11358416 What is the impact of early rheumatoid arthritis on the individual? 2001 Mar Rheumatoid arthritis has a significant impact on patients' physical, emotional and social functioning that often occurs very early in the disease with the onset of symptoms. Patients therefore come to their consultation with the rheumatologist, having often experienced these symptoms over a period of some months, with specific expectations (for reassurance and diagnosis) and their own understanding and beliefs about the aetiology and prognosis of their symptoms. Information and advice given by rheumatologists will be rejected by patients if it cannot be accommodated within these lay beliefs. The diagnosis itself can cause a variety of reactions, including relief, disbelief, anger, fear and devastation. Following diagnosis, patients are faced with the problems of adapting to a new self-concept, managing their symptoms and trying to assimilate the large amount of information that they are given about their disease, its treatment, preferred health behaviours, prognosis and so on. There are a number of ways in which health professionals can reduce this impact in early disease. Eliciting patients' lay beliefs about the cause of their symptoms will ensure that information given in the consultation is relevant to individual patients and is presented in a way that has meaning for them. Determining patients' expectations of the rheumatologist will ensure that patients' needs for information and reassurance are met and that unrealistic or inappropriate expectations can be discussed and re-negotiated. Understanding patients' attitudes towards treatment interventions will inform shared clinical decision-making and promote adherence. Obtaining this information in the context of a time-limited consultation can be assisted by the use of validated clinical tools, presented as self-completed questionnaires. Further research is needed to determine the content, frequency, timing and methodology of educational interventions in early rheumatoid arthritis and to improve the understanding of the complex interaction between lay beliefs and disease outcome.
11439164 Experimental chronic arthritis and granulomatous inflammation induced by bifidobacterium c 2001 Jul Effects of cell walls (CWs) from two almost identical strains of Bifidobacterium adolescentis were studied in rats, using three different doses. A single i.p. injection of both CWs triggered a long-lasting arthritis with CW degradation products present in the joint tissue. Histologically, the arthritis was characterized by inflammatory cells, synovial hyperplasia, pannus formation and bone erosion, closely resembling human rheumatoid arthritis (RA). In addition, CWs of the other strain induced a remarkable granuloma formation in the spleen and liver. Both CWs have the same peptidoglycan (PG) type A4alpha/beta, but differ from each other in three aspects. CW of the granuloma inducing strain: firstly has more lysine and less ornithine in PG stem peptides; secondly is more resistant to lysozyme degradation, and thirdly is better retained in the spleen. All these in comparison to the other strain used. Such characteristics are associated with the capacity to induce chronic arthritis, but it remains open how crucial they are for the granuloma formation.
11600945 [The Extensor Pollicis et Indicis: An Accessory or Rudimentary Deep Extensor Tendon to the 2001 Sep PURPOSE/BACKGROUND: Are the supernumerary deep extensor tendons to the thumb in man of accessory or rudimentary origin? METHOD AND CLINICAL MATERIAL: Two findings of extensor pollicis et indicis (EPI) were classified referring to the literature of comparative anatomy. RESULTS: Extensor pollicis longus (EPL) and extensor indicis (EI) developed phylogenetically from EPI. A common origin and proximal muscle belly of EPL and EI is a frequent manifestation of incomplete rudimentary EPI. A complete rudimentary EPI with absent EPL and EI has not yet been found in man. The accessory EPI coexisting with EPL and EI occurs in about 2 % of humans. CONCLUSION: During the EI-tendon transposition to EPL, the tendons must be identified very carefully because of the numerous variants of the deep extensors. Transposition of extensor digitorum communis of the index or just one tendon of a double-tendoned EI to EPL by mistake, will make separate extension of the thumb impossible postoperatively.
10441026 Role of the inflamed synovial volume of the wrist in defining remission of rheumatoid arth 1999 Aug The purpose of this study was to assess the role of inflamed synovial volume (ISV) in defining a state of remission in rheumatoid arthritis (RA) with contrast-enhanced, fat-suppression, three-dimensional (3D) gradient-recalled acquisition in the steady state with radiofrequency spoiling (SPGR) magnetic resonance (MR) imaging. Sixteen patients with RA (5 remission and 11 non-remission patients) were enrolled in this study. Contrast-enhanced, fat-suppression, 3D-SPGR MR imaging was performed before (n = 12) and after (n = 16) a mean 17 months of disease-modifying antirheumatic drugs (DMARDs). ISV was calculated by using a segmentation method. Statistical analysis of changes in ISVs and residual ISVs between the remission and the non-remission groups was performed. Intra- and inter-observer reproducibility was tested. Residual ISVs and relative changes in ISVs were 3.23 +/- 1.84 cm(3) and 51.4% (range 47.6-55.2%) in the remission group and 6.26 +/- 2. 03 cm(3)and 31.4% (range -73.5-53.5%) in the non-remission group. Both values were significantly different between the two groups (P < 0.05 and 0.05, respectively). Volume measurement showed high reproducibility: Intra- and inter-observer mean percentage errors were 5.04, 7.06, and 5.09%, respectively. Residual ISVs and relative changes in ISVs measured by MR imaging may provide objective and quantitative parameters in defining a state of remission in RA after therapy; however, the clinical utility of these measurements remains to be verified. J. Magn. Reson. Imaging 1999;10:202-208.
11477289 Renal type AA amyloidosis associated with rheumatoid arthritis: a cohort study showing imp 2001 Jul OBJECTIVE: To determine the incidence of renal AA amyloidosis and its association with rheumatoid arthritis (RA) in a cohort of all renal biopsies at one referral hospital and to measure the effect of a monthly pulse of cyclophosphamide on renal function and survival in these RA patients. METHOD: All renal biopsies with proven AA amyloidosis from a single pathology unit linked to a major nephrology referral unit in a university hospital were selected retrospectively and RA patients were identified. We studied 6931 renal biopsies. The effect of treatment with and without pulse cyclophosphamide on renal function and survival was studied in these patients. RESULTS: From March 1977 to February 1999, the incidence of AA amyloidosis was 2.4 cases/yr. The incidence and prevalence of the association of AA amyloidosis with RA were 0.68 cases/yr and 0.22% (15/6931) respectively. RA patients treated with cyclophosphamide (n=6) had a lower rate of renal function loss (P=0.013) and a higher median survival (P=0.026) than untreated patients (n=9). During the follow-up period, two out of six treated patients (33%) and all nine untreated patients (100%) died. CONCLUSIONS: AA amyloidosis is a rare complication of RA and complicates the evaluation of treatment. This retrospective study suggests that treatment with cyclophosphamide is able to reduce the incidence of end-stage renal failure and to increase survival. Prospective studies are needed to clarify this issue.
11247860 A prospective study of renal disease in patients with early rheumatoid arthritis. 2001 Apr OBJECTIVES: This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA). METHODS: 235 patients (185 women, mean age 49.4 years) with early RA of less than one year's duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of > or =5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities. RESULTS: At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low. CONCLUSIONS: This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.
9182921 Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. 1997 Jun OBJECTIVE: The repertoire of T cells in patients with rheumatoid arthritis (RA) is characterized by clonal expansion of selected CD4+ T cells, which are autoreactive and lack the expression of the functionally important CD28 molecule. The goal of this study was to determine the contribution of these unusual lymphocytes to the disease process. METHODS: RA patients (n = 108) and normal controls (n = 53) were examined for the expression of CD4+ CD28- T cells by 2-color fluorescence-activated cell sorter analysis. Clinical data were ascertained by retrospective chart review. RESULTS: The frequencies of CD4+ CD28- T cells displayed a bimodal distribution, defining carriers and noncarriers in normal subjects and RA patients. In longitudinal studies, the noncarrier and carrier phenotypes were stable over time. Carriers of CD4+ CD28- T cells accumulated in the RA population (64% versus 45%; P = 0.02). The expansion of CD4+ CD28- T cells correlated with extraarticular involvement, but not with disease duration, antirheumatic treatment, or severity of joint destruction. The patient subsets with nodular disease (P = 0.02) and rheumatoid organ disease (P = 0.04) had the highest proportion of CD4+ CD28- T cell carriers. The size of the CD4+ CD28- compartment correlated with extraarticular progression of RA (P = 0.001 in nodular RA, P = 0.003 in rheumatoid organ disease). CONCLUSION: The bimodality of distribution of CD4+ CD28- T cell frequencies is compatible with genetic control of the generation of these unusual T cells. In RA patients, CD4+ CD28- T cells are not an epiphenomenon of the disease process, but predispose patients to developing inflammatory lesions in extraarticular tissues.
10765982 Isolation and characteristics of autoreactive T cells specific to aggrecan G1 domain from 2000 Mar Our previous work showed that the cartilage proteoglycan aggrecan could induce an erosive polyarthritis and spondylitis in BALB/c mice and the G1 globular domain of the aggrecan (G1) contained the arthritogenic region. To elucidate whether autoreactive T cells to G1 are expressed in rheumatoid arthritis patients, we analyzed the frequency of human G1-specific T cells in the peripheral blood of five rheumatoid arthritis patients and tried to establish G1-reactive T cell lines from these rheumatoid arthritis patients. The results showed that the G1-specific T cells in PBL were detectable at the range of 4.97 +/- 0.5 x 10(-6) in peripheral blood lymphocytes. We have also generated 15 G1-specific T lymphocyte lines from these patients with a standard split-well method. All these cells expressed fine specificity to human recombinant G1, but not to unrelated antigen. All the 15 lines expressed a pan-T cell marker and 13 of them selectively used the alphabeta T cell receptor. Two of them used gammadelta T cell receptor. The 13 of these T cell lines was CD4 positive. One line expressed CD8. One line expressed both CD4 and CD8. Moreover, 14 out of 15 lines expressed the Th-1 cytokine profile, characterized by interferon-gamma positivity and IL-4 negativity. No Th-2 type cell line was generated. These data provide strong evidence in favor of the presence of autoreactive T cells in the rheumatoid arthritis patients. What is the mechanism(s) that these autoreactive T cells attack self-target and whether these G1-specific, Th-1 type T cell lines can induce arthritis in immune deficiency mice are currently under investigation.
9916387 Comparative studies of quality and bioavailability of methotrexate in Thai patients with r 1998 Dec The bioavailability of the two generic methotrexate oral preparations (Emtrexate, Pharmachemie Company, Holland and Methotrexate Remedica, Remedica, Cyprus as the test preparations), were compared to the innovator (Methotrexate Lederle, Lederle, U.S.A. as the reference) in 10 patients with rheumatoid arthritis. A single 7.5 mg oral dose of each preparation was given to the subjects in a randomized, double-blind, three-period crossover design with a 1 week washout period. Serum methotrexate concentrations were determined by using Fluorescence Polarization Immunoassay (Abbott TDx). No significant differences in pharmacokinetic parameters (AUC, Cmax, and Tmax) were observed between the test and reference preparations. The mean and 90 per cent CI of the ratio Emtrexate/Methotrexate Lederle and Methotrexate Remedica/Methotrexate Lederle of the Cmax, AUC0-8, and AUC0-alpha were 0.93 (0.87-1.00), 0.9 (0.82-0.98), 0.88 (0.79-0.99) and 0.97 (0.93-1.02), 0.95 (0.90-0.99), 0.94 (0.86-1.02), respectively. These values were well within the acceptable bioequivalence range of 0.8-1.25. The mean and 90 per cent CI of Tmax difference between Emtrexate-Methotrexate Lederle and Methotrexate Remedica-Methotrexate Lederle also overlapped the stipulated bioequivalence range of the Tmax differences of +/- 0.25 hour. Thus, Emtrexate and Methotrexate Remedica were considered bioequivalent to the reference Methotrexate Lederle regarding the rate of absorption and the extent of absorption.
11517739 [Double-blind trial of the effectiveness of antibodies to interferon-gamma and tumor necro 2001 AIM: Objective evaluation of the effectiveness and tolerance of antibodies to interferon-gamma (TNF-gamma) vs those to tumor necrosis factor-alpha (TNF-a) and placebo in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind randomised controlled trial of effectiveness and tolerance of anticytokine antibodies was conducted in 30 patients with active RA. The drugs were given i.m. for 5 consecutive days. The results were assessed on day 7 and 28. RESULTS: Antibodies to both cytokines produced a marked therapeutic effect in RA, much greater than placebo effect. Improvement by day 7 was achieved in 9, 7 and 2 patients on anti-TNF-a, anti-INF-g and placebo, respectively. By day 28 in 8, 8 and 0 patients, respectively. Tolerance of anticytokines was good. Significant differences between the results of treatment with anti-INF-g and anti-TNF-a were not found. CONCLUSION: Administration of antibodies to INF-a proved ineffective and well tolerated method in the treatment of severe RA resistant for a number of standard basic drugs. Anti-IFN-a holds great promise when used in combination with classic antirheumatoid drugs, primarily with methotrexate.
9933752 Association between HLA-DRB1*15 and Japanese patients with rheumatoid arthritis complicate 1999 Feb We performed serological phenotyping of HLA antigens in 175 patients with rheumatoid arthritis (RA) with (n = 41) and without (n = 134) renal involvement (RI), and DNA typing of HLA class II alleles in 75 patients. Among the patients with RA, the frequency of serologically determined HLA-DR4 was found to be significantly increased (odds ratio: 1.8, confidence interval: 1.3-2.5, p = 2.4x10(-4)). In the patients without RI, the frequency of serological DR4 significantly increased (odds ratio: 2.2, confidence interval: 1.6-3.3, p = 2. 6x10(-5)). On the other hand, among the patients with RI, a serological determinant, DR15, did significantly increase (odds ratio: 2.7, confidence interval: 0.9-8.4, p = 1.2x10(-3)) in comparison to the controls. At the DNA level, we found that the association of Japanese RA patients with serological HLA-DR4 was based on that with a genotype of HLA-DRB1*0405 (odds ratio: 2.4, confidence interval: 1.5-4.0, p = 4.4x10(-4)) and also found an association of HLA-DRB1*1501 (odds ratio: 2.8, confidence interval: 1.2-6.6, p = 0.017) with RA patients having RI. Our results confirmed the association of HLA-DRB1*04 with RA over the ethnic barrier at the DNA level. Our results also suggested a distinct genetic effect of HLA-DRB1*1501 in the aspect of the susceptibility of RI in RA.
11680793 Role of glycopeptide-specific T cells in collagen-induced arthritis: an example how post-t 2001 Oct Immunization of mice with type II collagen (CII), a cartilage-restricted protein, leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis (RA). CIA symptoms consist of an erosive joint inflammation caused by an autoimmune attack, mediated by both T and B lymphocytes. CD4+ alphabeta T cells play a central role in CIA, both by helping B cells to produce anti-CII antibodies, and by interacting with other cells in the joints, eg macrophages. In H-2q mice, most CII-specific CD4+ T cells recognize the CII(256-270) peptide presented on the major histocompatibility complex (MHC) class II Aq molecule. Post-translational modifications (hydroxylation and variable glycosylation) of the lysine residue at position 264 of CII generate at least four different T-cell determinants that are specifically recognized by distinct T-cell subsets. Most T cells recognize CII(256-270) glycosylated with the monosaccharide galactose, which is consequently immunodominant in CIA. Recent studies indicate that the arthritogenic T cells in CIA are glycopeptide-specific, suggesting that induction of self-tolerance may be rendered more difficult by glycosylation of CII. These data open the possibility that outoimmune disease may be caused by the creation of new epitopes by posttranslational modification of proteins under circumstances such as trauma, inflammation or ageing.
10796401 Antimalarials for rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0. 52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.