Rheumatoid Arthritis: China

Li M, Zhou Y, Feng G, Su SB. · Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China. · Curr Mol Med. · Pubmed #19355917 No free full text.

Abstract: Toll-like receptors (TLRs) form a large family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of microbial components and potential host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing proinflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. The dysregulation of TLR signaling may cause autoimmunity. This review discusses the contribution of TLR signaling to the initiation and progression of autoimmune diseases, such as rheumatoid arthritis, experimental autoimmune encephalitis, myocarditis, hepatitis, kidney disease, systemic lupus erythematosus, diabetes, obesity, and experimental autoimmune uveitis as well as aging. The involvement of TLR signaling in the pathogenesis of autoimmune diseases may provide novel targets for the development of therapeutics.

Su XH, Zhang ML, Zhan WH, Huo CH, Shi QW, Gu YC, Kiyota H. · School of Pharmaceutical Sciences, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang 050017, Hebei Province, P. R. China. · Chem Biodivers. · Pubmed #19235157 No free full text.

Abstract: The plants of genus Celastrus, distributed in Asia, have been used as natural insecticides and folk medicines to treat fever, chill, joint pain, edema, rheumatoid arthritis, and bacterial infection in China for a long time. This contribution reviews the chemical constituents, isolated from the plants in genus Celastrus in the past few decades, and their biological activities. The compounds listed are sesquiterpenes (beta-agarofurans), diterpenes, triterpenes, alkaloids, and flavonoids.

Kumana CR. · Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong. · Hong Kong Med J. · Pubmed #18840910 links to  free full text

Abstract: Horizons in Medicine is a series produced annually by the Royal College of Physicians. Volume 19 is based on their Advanced Medicine Conference held in 2007 and offers updates on a wide range of topics in clinical medicine. This 'review of reviews' covers developments described in a selection of chapters. The chapters summarised include: Contemporary management of acute myocardial infarction; Imported infectious disease emergencies; New therapies in the management of type 2 diabetes; Stress and adrenal insufficiency; Making sense of a 'funny thyroid function test'; Myeloproliferative disorders: management and molecular pathogenesis; Drug allergies; Osteoporosis; Rheumatoid arthritis; Understanding migraine from bench to bedside.

Sun J, Lin Z, Feng J, Li Y, Shen B. · Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 30072, PR China. · Eur J Pharmacol. · Pubmed #18793632 No free full text.

Abstract: Since B cell activating factor belonging to tumor necrosis factor (TNF) family (BAFF) has been identified as a critical factor for B cell maturation and survival, convincing evidence indicates that deregulation of BAFF is involved in pathogenesis of B cell related autoimmune diseases. Blockade of BAFF activity significantly improves the symptoms of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis both in animal models and clinical trials. Therefore, BAFF-targeting therapy is a promising approach to treat B cell related autoimmune diseases.

Xu M, Liu L, Qi C, Deng B, Cai X. · School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong Special Administrative Region, PR China. · Planta Med. · Pubmed #18683125 No free full text.

Abstract: Sinomenine (SIN), an alkaloid isolated from CAULIS SINOMENII, has been used in the treatment of rheumatoid arthritis (RA) clinically. This study aimed to systematically evaluate the efficacy and safety of SIN by a comparison between SIN and non-steroidal anti-inflammatory drugs (NSAIDs). Forty-three electronic databases were systematically searched. The quality of eligible trials was assessed by Jadad's scale. Revman 5.0 software was used for data syntheses and meta-analyses. The results showed that (i) of the 121 potential studies identified, 10 clinical trials involving 1185 patients met the inclusion criteria; (ii) improved patients and rheumatoid factor disappearance patients after SIN treatments were significantly more than those treated by NSAIDs ( P < 0.00001 and P = 0.008); (iii) compared with NSAIDs, SIN was more effective in amelioration of morning stiffness ( P < 0.00001), painful joints ( P = 0.03), and erythrocyte sedimentation rate ( P < 0.00001), but there was no significant difference between the two remedies in the treatment of swollen joints, grip strength, and C-reactive protein ( P > 0.05); and (iv) adverse events occurred less frequently in the digestive system during SIN treatment than during NSAID treatment ( P = 0.0003) but occurred more frequently in the dermatomucosal system with SIN treatment ( P = 0.03), while adverse events of the nervous system were similar for both treatments ( P = 0.31). In conclusion, SIN may be a valuable remedy to treat RA clinically, although current evidence needs to be further verified by more high-quality trials.

Tu G, Xu W, Huang H, Li S. · Department of Medicinal Chemistry, School of Pharmaceutical Sciences, ShanDong University, 44, West Culture Road, Ji'nan, 250012, P.R. China. · Curr Med Chem. · Pubmed #18537616 No free full text.

Abstract: Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation and remodeling of extracellular matrix proteins that are associated with the tumorigenic process. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function.Thus, MMP inhibitors (MMPIs) are expected to be useful for the treatment of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. A vast number of MMPIs have been developed in recent years.With the failure of these inhibitors in clinical trials,more efforts have been directed to the design of specific inhibitors with different Zn-binding groups. This review summarizes the current status of MMPIs, the design of small molecular weight MMPIs , a brief description of available three-dimensional MMP structures, a review of the proposed therapeutic utility of MMPIs, and a clinical update of compounds that have entered clinical trials in humans.

Zhao H, Yuan Y, Li Y, Si CW, Tian GS, Wang GQ, Yang XD. · Department of Infectious Diseases, Peking University First Hospital, 8, Xishiku Street, West District, 100034 Beijing, People's Republic of China. · Rheumatol Int. · Pubmed #18493768 No free full text.

Abstract: Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disorder, characterized by spiking high fever, fever-associated evanescent rash, arthritis, myalgia, serositis and hepatosplenomegaly. White blood cell count, neutrophilic cell count, and serum ferritin level are markedly elevated in the active stage of the disease. Neurological complications of AOSD commonly were cranial nerve palsies, seizures, aseptic meningoencephalitis, peripheral neuropathy and Miller-Fisher syndrome. We report a previously healthy 60-year-old Chinese man who fulfilled the criteria for AOSD and had a combination of focal and peripheral neurological symptoms. Magnetic resonance angiography (MRA) and transcranial Doppler ultrasonography (TCD) showed narrowness of cerebral blood vessel. Peripheral neuropathy was confirmed by electromyography and sural nerve biopsy. His generalized neuropathy and other symptoms were rapidly improved by receiving glucocorticoid therapy. We do a literature review about neurological manifestations observed in AOSD patients.

Zhang BG, Liu QF. · Chinese Traditional Medicine Research Institute of Henan University, Kaifeng 475001, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #17608234 No free full text.

Abstract: To discuss the general situation of the clinic utilization of Guizhi decoction in modem times. Look up the literature about the clinic utilization research of guizhi decoction in recent years, then to analyze and coordinate the useful informations. Guizhi decoction is widely used in clinic areas. The range of Guizhi decoction' treatment involves circulation, immunity, procreation, endocrine, digestion, nerve, etc. and covers various clinic illness such as internal medicine, surgery, gynaecology and obstetrics, pediatrics, ophthalmology and otorhinolaryngology, stomatology, etc.

Dai SM, Shan ZZ, Xu H, Nishioka K. · Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, P R China. · Ann Rheum Dis. · Pubmed #17502360 No free full text.

Abstract: Recent data are presented which indicate a critical role for interleukin (IL)-18 in rheumatoid arthritis (RA). The T cells and macrophages invading the synovium or in the synovial fluid are the chief cellular targets of IL-18 in RA. Neutrophils, dendritic cells and endothelial cells may also be cellular mediators of IL-18. The direct effect of IL-18 on fibroblast-like synoviocytes or chondrocytes may not be essential or important. In RA, IL-18, which is mainly produced by macrophages, activates T cells and macrophages to produce proinflammatory cytokines, chemokines, adhesion molecules and RANKL which, in turn, perpetuate chronic inflammation and induce bone and cartilage destruction.

Yang HP, Dai M, Zhang DH. · Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · Zhongguo Shi Yan Xue Ye Xue Za Zhi. · Pubmed #17493365 No free full text.

Abstract: Suppressor of cytokine signaling (SOCS) is a new family of proteins produced in cells. It may play an important role in classic negative feedback loop to regulate cytokine signal transduction. SOCS-1 was observed and confirmed firstly. Expression of SOCS-1 can inhibit cytokine signal transduction of some cytokines, such as IL-6, LIF, OSM, INF-gamma, GH, and so on, many immune responses are regulated by them in vivo. Abnormal expression of SOCS-1 is closely related to some human diseases. It plays an important role in the development of leukemia, rheumatoid arthritis, liver cirrhosis and liver cancer. In this review, the advances of research on the relationship between SOCS-1 and cytokine, and its correlation with some diseases were summarized.

Chen XP, DU GH. · Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. · Chin Med J (Engl). · Pubmed #17376315 links to  free full text

Abstract: OBJECTIVE: To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED (1997 - 2006) online resources using the key term LOX-1. STUDY SELECTION: Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. RESULTS: The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. CONCLUSIONS: Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.

Dai J, Rabie AB. · The Biomedical and Tissue Engineering Group, Department of Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China. · Orthod Craniofac Res. · Pubmed #17284242 No free full text.

Abstract: OBJECTIVES: To provide a comprehensive literature review describing recent developments of the recombinant adeno-associated virus (rAAV) vector and exploring the therapeutic application of rAAV for bone defects, cartilage lesions and rheumatoid arthritis. DESIGN: Narrative review. RESULT: The review outlines the serotypes and genome of AAV, integration and life cycle of the rAAV vectors, the immune response and regulating system for AAV gene therapy. Furthermore, the advancements of rAAV gene therapy for bone growth together with cartilage repair are summarized. CONCLUSION: Recombinant adeno-associated virus vector is perceived to be one of the most promising vector systems for bone and cartilage gene therapy approaches and further investigations need to be carried out for craniofacial research.

Liu CF, Lin N. · (Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #17165577 No free full text.

Abstract: Extracts of Tripterygium wilfordii are effective in traditional Chinese medicine for treatment of rheumatoid arthritis (RA). Triptolide, a diterpenoid triepoxide purified from TWHF, has been identified as the major component of TWHF and might account for its therapeutic effects. To make for the clinical reasonable application and further development of triptolide, in this review was introduced the recent ten-years progress in mechanisms of anti-RA of it, including immunosuppression, anti-inflammation, inducing cell apoptosis, inhibiting vascular proliferation, protecting article cartilage and gene regulation. Triptolide is a potent immunosuppressant.

Chen J, Liu C, Lin J. · TheFirst Affiliated Hospital of Fujian Medical University, Department of Hematology and Rheumatology, Fuzhou, Fujian Province, China. · Cochrane Database Syst Rev. · Pubmed #17054209 No free full text.

Abstract: BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterised by sacroiliitis and spondylitis. Generally, treatment is limited to the alleviation of symptoms using non-steroidal anti-inflammatory drugs (NSAIDs). Recently, disease-modifying antirheumatic drugs (DMARDs) have been used for patients for whom NSAIDs do not work. Methotrexate (MTX), a widely used DMARD, is effective for rheumatoid arthritis (RA), and so might work for AS too. OBJECTIVES: To evaluate the efficacy and toxicity of MTX for treating AS. SEARCH STRATEGY: We conducted searches in any language in: CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 20, 2005); EMBASE (1980 to November 20, 2005); CINAHL (1982 to November 20, 2005), and the reference sections of retrieved articles. SELECTION CRITERIA: Randomised and quasi-randomised trials examining the efficacy of MTX versus placebo, other medication, or no medication, for AS. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed unblinded trial reports for inclusion, assessed methodological quality and entered trial data into RevMan 4.2 using the double-entry facility. Disagreements were resolved by a third reviewer. In the absence of significant heterogeneity, results for continuous data were combined using weighted mean difference or standardised mean difference. Relative risk was used for dichotomous data. MAIN RESULTS: Three trials, involving 116 patients, were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. Only the response rate in one trial showed a statistically significant benefit of 36% in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX is questionable. No serious side effects were reported in these trials. AUTHORS' CONCLUSIONS: There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality randomised controlled trials of longer durations and with larger sample sizes are needed to clarify the effect(s) of MTX on AS.

Mok MY, Wong SY, Chan TM, Tang WM, Wong WS, Lau CS. · University Department of Medicine, Queen Mary Hospital, Hong Kong. · Lupus. · Pubmed #16830885 No free full text.

Abstract: Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1-27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality.

Zheng RL, Lv H, Zhang W, Yu MX, Yuan Y. · Department of Neurology, Peking University First Hospital, Beijing 100034, China. · Beijing Da Xue Xue Bao. · Pubmed #16778982 No free full text.

Abstract: To report the clinical, radiological and neuropathological findings of a patient with rheumatoid meningitis. The patient was a 71-year-old Chinese man with a two-year history of rheumatoid arthritis and no other significant medical history, who presented to our hospital recurrent weakness of his left extremities, dysarthria and a continuous bilateral hand tremor. Cerebrospinal fluid (CSF) and serum examinations were normal apart from a mildly raised serum perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA). Brain magnetic resonance imaging (MRI) showed leptomeningeal enhancement in both frontal and parietal lobes, in addition to several old white matter infarcts. Meningeal biopsy showed numerous infiltrating macrophages and lymphocytes within the leptomeninges. The patient responded clinically and radiologically to corticosteroid and cyclophosphamide therapy. The patient subsequently developed herpes zoster over his left chest as a complication of his immunosuppressive treatment. His cyclophosphamide was ceased and intravenous immunoglobulin (IVIG) therapy was commenced, with good clinical response to both the herpes zoster and meningitis. According to the result of the biopsy, aseptic meningitis was considered the MRI results and the patient's clinical history were given, and a diagnosis of rheumatoid meningitis was made. The patient was p-ANCA positive. Although there was no evidence for cerebral vasculitis on biopsy, it remains a possibility that the patient's recurrent minor cerebral infarcts visible on MRI were vasculitic in nature.

Zhu J, Yu DT. · Rheumatology Department, Chinese PLA General Hospital, Beijing, China. · Curr Opin Rheumatol. · Pubmed #16763456 No free full text.

Abstract: PURPOSE OF REVIEW: Expression of matrix metalloproteinases and their tissue inhibitors has been an active area of investigation in rheumatoid arthritis and osteoarthritis. Only recently have investigators started to study these factors in spondyloarthropathy. The purpose of this review is to summarize these recent findings. RECENT FINDINGS: Multiple matrix metalloproteinases and their tissue inhibitors are expressed in the synovial fluid as well as serum samples of spondyloarthropathy patients. Their degrees of expression in the synovia correlate with parameters of arthritis activity such as cell infiltration. In the synovial fluids, the factor which is expressed in very high level is matrix metalloproteinase-3. Two separate cohorts demonstrate that serum levels of matrix metalloproteinase-3 correlate with disease activity in ankylosing spondylitis. Their usefulness appears to exceed those of erythrocyte sedimentation rate and C-reactive protein. Multiple studies also indicate that serum levels of matrix metalloproteinase-3 are suppressed when patients are treated with the anti-tumor necrosis factor-alpha antibody infliximab. SUMMARY: New biomarkers are in demand for spondyloarthropathy in deciding whether patients would benefit from treatment with tumor necrosis factoralpha blockers, monitoring response to treatment, or predicting potential of joint damage if untreated. Recent studies show that among the matrix metalloproteinase and their tissue inhibitors, serum MMP-3 is the one with potential usefulness.

Zhang LF, Zhao JX. · Dozhimen Hospital of Beijing of University Traditional Chinese Medicine, Beijing 100700, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #16494017 No free full text.

Abstract: The functions of Euonymus alatus in herbal canon, are removing blood stasis, restoring menstrual flow and killing worms, especially for gynecological diseases. The recently researches show E. alatus can depress blood sugar and blood lipid, resist hypersusceptibility, regulate immunity, and calcium abundant. It is effective for diabetes, hyperglycemia, chronic nephropathy, rheumatoid arthritis, urinary tract infection and prostate diseases, etc internal diseases, no matter singleness or together with other herbs.

Xu W, Li Q. · Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shan Dong University, 44 West Culture Road, Ji'nan 250012, P.R.China. · Curr Med Chem Anticancer Agents. · Pubmed #15992355 No free full text.

Abstract: Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesis of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.

Lu AP, Wu P, Ju DH, Jia HW, Li S, Xu SJ, Zhao N, Xiao C, Wu H, Teng JR, Li Y, Wang SJ, Zhou GQ, Zhang H, Wang AM. · Institute Of Basic Theory, China Acaemy Of Tradtional Chinese Medicine · Zhongguo Zhong Yao Za Zhi. · Pubmed #15988837 No free full text.

This publication has no abstract.

Cao W, He W. · Peking Union Medical College, Dong Dan San Tiao 5, Beijing 100005, People's Republic of China. · Immunobiology. · Pubmed #15518340 No free full text.

Abstract: According to present concepts, innate immunity plays an important role in tumor surveillance and immune modulation. The state of NK cells depends on the balance between inhibitory and activating signals from corresponding receptors. As one of the activating receptors, NKG2D recognises some self ligands such as MICA/B in human and Rae1 in mice, which is dissimilar to those toll-like receptors that recognise some pathogen-derived ligands. NKG2D is expressed not only on NK cells, but on gammadelta T cells, CD8+ alphabeta T cells in normal individuals and CD4+ alphabeta T cells in rheumatoid arthritis patients and plays a different role on respective cells. Whereas NKG2D can only function as a costimulatory receptor on CD8+ alphabeta T cells under the domination of alphabeta TCR in spite of a deficiency of costimulatory molecule CD28, NKG2D can directly activate NK cells even in the presence of inhibitory signals from MHC-I and corresponding receptor complexes. Experiments in mice have identified that alternative splicing produces two distinct NKG2D polypeptides that associate differentially with the DAP10 and DAP12 signaling subunits and that differential expression of these isoforms and of signaling proteins determines whether NKG2D only functions as a costimulatory receptor in the adaptive immune system (CD8+ T cells) or as both a primary recognition unit and a costimulatory receptor in the innate immune system (natural killer cells and macrophages). This review summarizes the research achievements in a new ligand family (UL16 binding proteins) of NKG2D in human and shows the possible prospects of ULBP function and application.

Mok MY, Lo Y, Leung PY, Lau CS. · Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. · J Rheumatol. · Pubmed #15517651 No free full text.

Abstract: Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not been addressed. We report the maternal and fetal morbidity of 5 pregnancies from 3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients reported in the English literature. Nine patients had their first manifestation in the 5th to 6th gestational month. Disease relapse in patients with known AOSDoccurred most commonly in the post-partum period. Most did not respond satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to administration of corticosteroids, especially in high doses.

Li EK, Tam LS, Tomlinson B. · Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, ROC. · Clin Ther. · Pubmed #15189743 No free full text.

Abstract: BACKGROUND: Current drug therapies for rheumatoid arthritis (RA), including nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs, help control inflammation but can cause significant toxicity. Drugs are needed that are able to suppress inflammation and modify the underlying immune response with improved tolerability. Leflunomide is an agent that affects the inflammatory process, particularly in RA. OBJECTIVE: This paper reviews the pharmacology of leflunomide, its approved use in RA, and the results of major clinical trials, including adverse events. METHODS: Relevant trials were identified through a search of the English-language literature indexed on EMBASE, MEDLINE, Current Contents, and the Cochrane Controlled Trials Register from January 1980 to November 2003. Search terms were limited to leflunomide. RESULTS: In 3 large Phase III clinical trials (US301, MN301, and MN302), leflunomide had equivalent clinical efficacy and tolerability to methotrexate and sulfasalazine and superior efficacy and tolerability compared with placebo. In US301 (N = 482), the ACR (American College of Rheumatology) 20 response rate (proportion of patients with > or =20% improvement from baseline in tender and swollen joint counts, patient's assessment of pain, patient's and physician's global assessment of disease activity, physical function, and acute-phase reactant value) at 1 year was similar with leflunomide and methotrexate and significantly greater with both active treatments than with placebo (52%, 46%, and 26%, respectively; both, P < 0.001). The efficacy of leflunomide was seen early (after 4 weeks of treatment) and was sustained throughout the study. There was less radiographic damage in both active-treatment groups compared with placebo (leflunomide, P < or = 0.001; methotrexate, P = 0.02). In MN301 (N = 358), the ACR20 response rate at 6 months was similar with leflunomide and sulfasalazine and significantly greater with both active treatments compared with placebo (55%, 56%, and 29%, respectively; both, P < 0.001). Radiographic progression was also similar with leflunomide and sulfasalazine, both of which were significantly superior to placebo (Larsen score, 0.42, 0.41, and 1.4; both, P < 0.001). An extension of this study revealed maintenance of efficacy at 12 and 24 months. In MN302 (intent-to-treat population, N = 999), 50.5% of patients in the leflunomide group were ACR20 responders at the end of 1 year, compared with 64.8% in the methotrexate group (P < 0.001 vs leflunomide). After 2 years, ACR20 response rates were similar with leflunomide and methotrexate (64.3% and 71.7%). The overall safety profile of leflunomide appears promising, although monitoring for elevations in liver enzymes and bone marrow suppression is recommended. The most common drug-related adverse events associated with leflunomide in these clinical trials were diarrhea, abnormalities in liver enzymes, rash, and hypertension.

Wu H, Geng P. · Qinghai College of Medicine, Xining 810000, Qingghai Province, China · Zhong Yao Cai. · Pubmed #14730716 No free full text.

This publication has no abstract.

Liu H, Tong F. · College of Zoological Sciences, Zhejiang University, Hangzhou 310029, Zhejiang, China. · Zhong Yao Cai. · Pubmed #14669739 No free full text.

This publication has no abstract.