双氯芬酸二乙胺乳胶剂联合甲氨蝶呤治疗银屑病性关节炎疗效观察

目的探讨双氯芬酸二乙胺（扶他林）乳胶剂联合甲氨蝶呤治疗银屑病性关节炎的临床疗效。方法将32例银屑病性关节炎患者随机分为一组和二组,每组16例。一组局部外用扶他林乳胶剂联合甲氨蝶呤治疗,二组单独使用甲氨蝶呤,疗程均为6周。观察并比较2组临床疗效。结果治疗6周后,一组总有效率为93.8%高于二组的81.2%,差异有统计学意义（P〈0.05）;且不良反应轻微。结论局部外用扶他林乳胶剂联合甲氨蝶呤治疗银屑病性关节炎安全有效。     

来氟米特加甲氨蝶呤治疗银屑病关节炎的疗效观察

目的：研究来氟米特加甲氨蝶呤治疗银屑病关节炎（PSA）疗效和安全性。方法：39例PsA患者分为治疗组和对照组,治疗组用来氟米特加甲氨蝶呤治疗,对照组用甲氨蝶呤治疗,疗效为12周。分别对两组在6周、12周时进行疗效评估。结果：治疗组在6周、12周时的有效率为55.5％、88.9％,对照组为47.6％、61.9％。显示来氟米特加甲氨蝶呤对PsA的疗效比单用甲氨蝶吟好,能显著改善临床症状和疾病的活动性指标,不良反应二者相当。结论：来氟米特加甲氨蝶呤为治疗PsA的有效治疗方案,且相对安全。     

药物性肝炎344例临床分析

目的:探讨药物性肝炎的病因、临床特点及治疗.方法:回顾性分析我院2004～2009年收治的药物性肝炎344例的临床资料,通过对基础病、用药种类、临床表现、实验室检查及临床转归等总结其发病规律及特点.结果:引起药物性肝炎的基础病主要为肺结核、糖尿病、甲亢、风湿性关节炎、精神性疾病等;引发药物性肝炎的药物种类较多,主要以中药、抗结核药、抗生素为主;临床表现乏力、纳差、尿黄、眼黄、身黄、恶心、皮肤瘙痒等;停药及保肝治疗后治愈率93.9%,肝衰竭发生率6.1%,死亡率0.9%,发生肝衰竭以抗结核药为主,其次为中药.人工肝支持治疗药物性肝炎,可明显降低病死率,缩短病程.结论:应高度重视药物性肝炎,注意了解药物的成分、适应证、禁忌证,影响药物性肝炎的因素主要有用药种类、用药时间及是否合并乙肝等.     

Autoimmune hepatitis after long-term methotrexate therapy for rheumatoid arthritis

Methotrexate (MTX) therapy may be effective in patients with rheumatoid arthritis (RA) or psoriasis due to its anti-inflammatory and immunosuppressive properties. Potential liver toxicity of MTX exists, but the incidence of MTX-specific lesions in liver biopsy of patients with RA and elevated serum transaminase levels is rare; however, severe hepatic damage may occurs unexpectedly in these patients. We describe the first documented case of an adult patient with RA who developed an acute flare of severe hepatitis after long-term therapy with MTX. Autoantibodies positivity, elevated serum IgG levels and compatible liver biopsy findings prompted us to diagnose autoimmune hepatitis, most probably triggered by a breakdown of immune tolerance induced by MTX. A complete remission was achieved in this patient with corticosteroids therapy.     

Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.     

Enzymes as target antigens of liver-specific autoimmunity: the case of cytochromes P450s

Characterization of liver-specific autoantigens has given a fresh impetus to research in the pathogenesis of autoimmune liver diseases, viral-triggered and drug-induced autoimmunity affecting the liver. Intriguing is the fact that most of the liver-specific autoantigens are enzymes of key importance for cell's homeostasis. Detection of autoantibodies against the respective antigens is carried out for diagnostic and research purposes using indirect immunofluorescence, immunoblotting, enzyme-linked immunosorbent assays, radioimmunoassay, immunoprecipitation or assays determining inhibition of enzyme activity. In patients with autoimmune hepatitis, a liver disorder of unknown etiology and pathogenesis, disease-specific autoantibodies are frequently directed against drug metabolizing enzymes of phase 1, namely cytochrome P450 2D6 (CYP2D6). The same and other members of these families of enzymes (CYPs) have also been described as targets of liver-specific autoimmunity in chronic hepatitis C virus (HCV)-infected patients, patients with autoimmune hepatitis as part of the autoimmune polyglandular syndrome type-1 (APS-1) and drug-induced autoimmunity. How these enzymes become 'self targets' is not yet established. An antigen release following hepatocyte injury could provide the stimulus for an immune response towards epitopes on these enzymes but the highly-specific, antigen-restricted initiation of the observed autoimmune response is against such an explanation. Accordingly, in this review we will focus on the pathogenic role -if any- of autoimmune responses against liver-related CYPs in autoimmune hepatitis, HCV infection, APS-1 and drug-induced autoimmunity. Learning more about the specificity of antibody responses against these enzymes may help us better understand the mechanisms underlying liver autoimmunity and may facilitate the development of therapeutic and preventive interventions.     

药物诱导的自身免疫性肝炎

自身免疫性肝炎（AIH）是机体自身的免疫系统破坏肝细胞导致的一种肝脏慢性炎症性疾病。一般认为，AIH的发生与遗传因素和环境因素的共同作用有关。诱发AIH的环境因素有病毒、毒素及药物等。就药物而言，米诺环素、干扰素、他汀类药物、氯美辛和英夫利昔单抗等均能诱发具有遗传易感性患者的肝细胞损伤。药物诱发的自身免疫性肝炎（DAIH）通常发生在用药后2～24个月；约80％～90％患者为女性。DAIH的临床表现为乏力、食欲不振、上腹部不适，黄疸、肝肿大，常伴有发热、皮疹及关节疼痛。DAIH的临床特征有：发病率低；与剂量无关；用药与发病之间有一长时间的间隔；出现高丙种球蛋白血症和高滴度自身抗体（如ANA、ASMA）。目前治疗DAIH的有效方法为免疫抑制。大多数患者的病情在应用糖皮质激素单独治疗或与硫唑嘌呤联合治疗后改善。     

Efficacy and safety of adalimumab treatment in patients with rheumatoid arthritis,ankylosing spondylitis and psoriatic arthritis

Introduction: In the last couple of years, the number of patients with chronic inflammatory rheumatic diseases being treated with TNF α antagonist has increased dramatically. Adalimumab, a fully human monoclonal antibody against TNF α, is one of the most frequently administered TNF α antagonists. Yet, unresolved issues are the long-term safety of TNF α antagonists and high treatment costs.

Areas covered: The authors summarize the available data on short- and long-term efficacy and safety of adalimumab in the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The reader will find a comprehensive overview on the safety and efficacy of adalimumab for these conditions. Clinically relevant questions of adalimumab therapy are discussed. A special focus of this review is on the safety of adalimumab therapy.

Expert opinion: Adalimumab is effective and reasonably safe in the short- and long-term treatment of patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who do not respond to the standard therapy. It inhibits radiographic progression in rheumatoid and psoriatic arthritis. Treatment with a TNF α inhibitor such as adalimumab is associated with high treatment costs.     

Drug-induced lupus

Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.     

Clinical monograph for drug formulary review: systemic agents for psoriasis/psoriatic arthritis

BACKGROUND: Significant advances in the pharmacologic treatment of psoriasis, most notably the introduction of the biologic agents efalizumab and alefacept, have occurred recently. In addition, another biologic agent, etanercept, was recently approved for the treatment of psoriasis and psoriatic arthritis, thus adding to the list of biologic agents approved for the treatment of these disease states. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used systemic agents for the treatment of psoriasis and psoriatic arthritis. OBJECTIVE: To provide readers with a comprehensive clinical monograph on psoriasis and psoriatic arthritis agents, written with a managed care perspective, as used in actual drug formulary decision making by a PBM. METHODS: The drug formulary of this PBM is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UpToDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs produced by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: The biologic agents do not appear to be as efficacious as traditional systemic therapies but are associated with fewer long-term toxicities that often limit treatment duration with traditional systemic agents. Although no head-to-head comparisons between alefacept and efalizumab exist, efalizumab appears to offer slightly higher efficacy rates, while alefacept has a longer duration of action. Etanercept at the higher approved dose appears more efficacious compared with efalizumab or alefacept for the treatment of psoriasis, and it is the only biologic currently approved for the treatment of psoriatic arthritis. Efalizumab and alefacept are generally well tolerated, but rebound flare of psoriasis is associated with efalizumab, thus requiring continuous treatment to avoid a flare in disease. Efalizumab and etanercept can be self-administered by the patient, while alefacept and infliximab require administration by a health care professional. CONCLUSIONS: Systemic therapy is reserved for patients with moderate-to-severe psoriasis or patients with psoriatic arthritis. The biologic agents are not as efficacious as traditional therapies but, due to better tolerability, are gaining acceptance in the treatment of psoriasis and psoriatic arthritis. The biologic agents differ in efficacy rates and are generally well tolerated. Clinical attributes, overall efficacy, and economic costs associated with the biologic agents will be significant factors in selecting agents for the treatment of psoriasis and psoriatic arthritis.     

Efficacy and safety of adalimumab treatment in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis

INTRODUCTION: In the last couple of years, the number of patients with chronic inflammatory rheumatic diseases being treated with TNF α antagonist has increased dramatically. Adalimumab, a fully human monoclonal antibody against TNF α, is one of the most frequently administered TNF α antagonists. Yet, unresolved issues are the long-term safety of TNF α antagonists and high treatment costs. AREAS COVERED: The authors summarize the available data on short- and long-term efficacy and safety of adalimumab in the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The reader will find a comprehensive overview on the safety and efficacy of adalimumab for these conditions. Clinically relevant questions of adalimumab therapy are discussed. A special focus of this review is on the safety of adalimumab therapy. EXPERT OPINION: Adalimumab is effective and reasonably safe in the short- and long-term treatment of patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who do not respond to the standard therapy. It inhibits radiographic progression in rheumatoid and psoriatic arthritis. Treatment with a TNF α inhibitor such as adalimumab is associated with high treatment costs.     

Investigation of the Mechanism of Therapeutic Protein-Drug Interaction Between Methotrexate and Golimumab,an Anti-TNFα Monoclonal Antibody

A prominent example of human therapeutic protein-drug interaction (TP-DI) is between methotrexate (MTX) and anti-TNFα mAbs. One plausible mechanism for this TP-DI is through the pharmacodynamic effect of MTX on immunogenicity. However, there is no definitive evidence to substantiate this mechanism, and other competing hypotheses, such as MTX suppressing FcγRI expression thereby affecting mAb PK, have also been proposed. In order to understand this mechanism, a cynomolgus monkey study was conducted using golimumab as a model compound. Golimumab elicited high incidences of immunogenicity in healthy cynomolgus monkeys. Concomitant dosing of MTX delayed the onset and reduced the magnitude of anti-drug antibody (ADA) formation. The impact of MTX on golimumab PK correlated with the ADA status. Prior to ADA formation, MTX has no discernable effect on golimumab PK. Additionally, no alteration in FcγRI expression was observed following MTX treatment. The impact of MTX on golimumab immunogenicity and PK has been observed in patients with rheumatoid arthritis, psoriatic arthritis (PsA), and ankylosing spondylitis. In a representative phase 3 study of golimumab in patients with PsA, patients not receiving concomitant MTX was reported to have ~?30% lower steady-state trough golimumab levels compared to those who received MTX. However, further analysis showed that PsA patients who were negative for ADA in both treatment groups had comparable trough levels of golimumab. Taken together, our results suggest that the mechanism of TP-DI between MTX and golimumab can mostly be attributed to the pharmacodynamic effect of MTX, i.e., the lowering of immunogenicity and immunogenicity-mediated clearance of mAbs.     

Adalimumab: in psoriatic arthritis

Adalimumab, a fully human monoclonal antibody, is a tumour necrosis factor antagonist that has been investigated for efficacy in psoriatic arthritis, based on well-established use of the drug in rheumatoid arthritis. In well-controlled Phase III trials, adalimumab (40 mg administered subcutaneously every other week) has shown efficacy in adult patients with psoriatic arthritis who had an inadequate response to previous treatment with NSAIDs (24-week ADEPT trial; n = 313) or disease-modifying antirheumatic drugs (12-week study; n = 100). In these trials, adalimumab recipients experienced a significantly greater improvement in arthritis response (p < 0.001 in the ADEPT trial, and p 相似文献   

In vivo effects of high-dose methotrexate on bone remodeling in rats

Methotrexatae (MTX) is a folate antagonist. MTX osteopathy is well recognized to accompany a high-dose therapy with this drug for the treatment of childhood malignancy. Clinical tests also show that low-dose MTX used in the treatment of rheumatoid arthritis may impair bone formation in a population already predisposed to osteoporosis. However, results of clinical tests are hard to interpret, as it is necessary to take into account malignancy-induced changes in the osseous tissue, long-term immobility and concurrent administration of glucocorticosteroids. We conducted in vivo tests to evaluate the effects of oral and intramuscular administration of high dose of MTX on bone remodeling processes in rats. Effects of MTX on the processes of bone remodeling were evaluated by assessing macrometric and histomorphometric parameters as well as mechanical properties of the femur. The tests were carried out on male Wistar rats. Animals were divided into four groups, composed of 7 animals each: Control group (0.9% NaCl solution), MTX-1 po group (MTX at the dose of 1 mg/kg po daily for 10 days: every day for the first five days, and after an 18-day interval, every day for five days), MTX-1 im group (MTX at the dose of 1 mg/kg im daily for 10 days: every day for the first five days, and after an 18-day interval, every day for five days), MTX-5 im group (MTX at the dose 5 mg/kg im daily for 2 days a week for the period of four weeks). Changes in bone remodeling were examined 4 weeks after the first MTX administration. These results show that MTX administered intramuscularly at high doses inhibited the formation and mineralization of new osseous matrix and impaired mechanical properties of the femoral bone, whereas its oral administration had no effect on bone remodeling in rats.     

Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from adalimumab studies

In recent years, there have been major advances in the management of rheumatoid arthritis (RA), leading to the development of tumour necrosis factor (TNF) antagonists. With these agents, it is possible to arrest joint damage and, by treating early in the disease course, to prevent joint damage. It is also now thought that early treatment can achieve clinical remission in a substantial proportion of patients. With these increased expectations, a change is required in the way clinical improvement and drug efficacy is measured. The existing standard endpoint commonly used in RA clinical trials, the American College of Rheumatology (ACR) 20% response measure, is inadequate for the new goals of therapy that should be based on clinical remission and radiographic assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown to be effective in achieving remission and preventing radiographic progression of joint damage in patients with RA and other inflammatory arthropathies, including psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in patients with early RA, combination treatment with adalimumab plus methotrexate (MTX) has been shown to be superior to either treatment alone in inducing significant clinical remission while being generally well tolerated. Compared with monotherapy, combination therapy resulted in significantly more patients (49% vs 25%; p < 0.001) remaining in clinical remission after 2 years. Suppression of joint damage assessed by the degree of inhibition of radiographic progression was also significantly higher for patients treated with adalimumab plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those treated with MTX alone. These data support the notion that clinical remission is a realistic therapeutic goal in patients with RA.     

Etanercept Immunex

Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of early and moderate to severely active rheumatoid arthritis (RA). Etanercept was launched as a first-line agent in the US for the treatment of moderate-to-severe active RA in June 2000 [375481]. It can also be used in conjunction with methotrexate (MTX) in patients who do not respond adequately to MTX alone [303266], [310436]. It was launched in the EU in November 2000 [388846]. Enbrel was also launched for the treatment of polyarticular-course juvenile RA (JRA) patients who have an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs) in May 1999. Additionally, it is in phase III trials for psoriatic arthritis and a BLA filing for this indication is expected for the first half of 2001 [364948]. Etanercept was launched in the US in November 1998, for the treatment of moderate-to-severe RA in patients with inadequate responses to one or more DMARDs, or in combination with MTX in patients who do not respond adequately to MTX alone [306175]. The drug was subsequently approved by the US FDA for use as a first-line therapy to treat patients with moderately to severely active RA [375481]. In February 2000, Wyeth Europe received clearancefor etanercept in 15 EU countries by the EMEA for the treatment of active arthritis in adults when the response to DMARDs has been inadequate [354844]. It has since been launched in the UK (June 2000) [388840], and by October 2000 had been launched in all EU member states [388846]. In November 1998, the company filed a supplemental BLAfor the treatment of children and teenagers with moderately to severely active polyarticular course JRA. In May 1999, etanercept was approvedfor this indication by the US FDA and approvedfor this indication in Europe in February 2000 [307061], [310436], [326379]. The increasing understanding of the role of TNF in a number of other diseases has led to its clinical assessment in these areas. Following positive clinical results in phase II studies [317562], [315793], (320666], (359789], (373980] in patients with chronic heart failure, etanercept entered phase III trials for this indication in June 1999 [330068], and a BLA filing for this indication is expected in 2003 [396110]. Additionally, Immunex initiated a phase III trial of etanercept in psoriatic arthritis in March 2000, and as of May 2000, the company was planning a BLA filing for this indication in the first half of 2001 [364948]. An open-label trialfor the treatment of Crohn's disease is in progress in Belgium [367,039], and results from this trial were presented at Digestive Disease Week in May 2000 [379907]. While WO-09103553 claims the recombinant human receptor, the fusion protein consisting of the etanercept domain and the immunoglobulin region was disclosed in WO-09406476. In February 1997, US-05605690 was issued to Immunex for methods of using etanercept to treat diseases mediated by TNF. The patent also claims methods of using recombinant etanercept to decrease the levels of TNF in RA patients [235456]. In June 1999, Immunex strengthened its patent estate covering the product with a patent licensing agreement for Genentech's immunoadhesin patents covering the product [327250]. A royalty agreement with Serono SA and Immunex on sales of etanercept was agreed in 1999. The agreement reflected the strength of Ares-Serono's intellectual property status [352813]. In June 1999, Lehman Brothers predicted Immunex's sales at US $300 million in 1999, rising to peak annual sales of US $1.5 billion [328701]. Salesfor the drug's first full quarter on the market in 1999 were US $59.7 million [330068]. By November 1999 the drug had made sales of US $500 million; Immunex expects the drug will generate over US $2 billion in annual sales by 2004 [353185]. In September 2000, Merrill Lynch reported that if sales of the drug continue at the present rate then it is likely that demand will temporarily outstrip supply in 2001. Resolution of the supply issue is expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of ENBREL sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believe that the drug has the potential to exceed US $5 billion in sales in the US [382577].     

云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎的远期疗效观察

目的:观察云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎的远期疗效。方法:将57例类风湿关节炎患者分为2组,治疗组30例采用静脉滴注云克,口服甲氨蝶呤+来氟米特治疗;对照组27例采用单纯口服甲氨蝶呤+来氟米特治疗。观察治疗前及治疗后4、12周时的关节症状、实验室指标变化,并评价其疗效和不良反应。结果:治疗4周后,治疗组达到美国风湿病学会(ACR)20为27例(90.00%),ACR50为7例(23.33%);对照组达到ACR20为18例(67.00%),ACR50为0,2组比较差异均有统计学意义(P<0.05);治疗后12周治疗组达到ACR50为21例(70.00%),ACR70为9例(30.00%);对照组达到ACR50为9例(33.33%),ACR70为2例(7.41%),2组比较差异有统计学意义(P<0.01)。2组不良反应比较差异无统计学意义(P>0.05)。结论:云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎远期效果、安全性好。     

阿克他利治疗类风湿关节炎29例

目的探讨阿克他利(ACT)治疗类风湿关节炎(RA)的疗效和安全性。方法采用随机、双盲、平行对照的研究方法,以甲氨蝶呤(MTX)为阳性对照药。共入选病例60例,ACT组29例,用ACT 100 mg,po,tid;NIX组31例,用MTX 10 mg,po,qw。12 wk为1个疗程,其中ACT和MTX组分别有21和19例完成2个疗程。结果治疗12和24 wk后,ACT组总有效率为55.17%和66.67%,MIX组总有效率为60.00%和73.68%,2组间疗效比较差异无统计学意义(P>0.05)。ACT能显著改善患者的症状和体征(P<0.05),但2组间改善程度相比差异无统计学意义(P>0.05)。12和24 wk时,ACT组的不良反应发生率分别为10.34%和13.79%,MTX组为16.13%和22.58%(P>0.05)。结论ACT是一个安全性好且具有较好疗效的治疗RA的新型抗风湿药。     

Hepatitis Caused by Lotus‐f3?

Abstract: We present a case of hepatitis and jaundice are associated with ingestion of Lotus‐f3 submitted to our regional pharmacovigilance centre. A 56‐year‐old woman with psoriatic arthritis developed increased liver enzymes and jaundice 3 weeks after having started to take the product. The woman had been treated with etanercept for more than a year. She was hospitalized with hepatitis, and viral causes were ruled out. Liver biopsy suggested autoimmune or toxic hepatitis. Both etanercept and Lotus‐f3 were withdrawn, and 6 weeks later the liver enzymes were normalized without any treatment. Etanercept was subsequently successfully reintroduced, and based on the rapid resolution of the hepatitis, a toxic effect of Lotus‐f3 was suggested. This was the first report in the national adverse drug reaction database for this product, but three similar cases have now been reported. Lotus‐f3 contains an extract of green tea, which has been associated with hepatotoxicity. The Norwegian adverse drug reaction database contains nine reports of hepatitis or jaundice associated with natural products. Four different natural products containing extracts of green tea have been suspected in eight out of these nine reports.     

TNF inhibitors in the treatment of arthritis

Rheumatoid arthritis (RA) is a chronic destructive arthritis leading to joint destruction as a consequence of chronic inflammatory processes. Established therapy with slow-acting disease-modifying anti-rheumatic drugs (DMARDs), as with low-dose methotrexate (MTX), leads to a significant improvement of disease symptoms, but are unable to stop joint destruction. Novel therapeutic agents like monoclonal antibodies (mAb), cytokine receptor-human immunoglobulin constructs or recombinant human proteins have been tested in RA and in other chronic arthritides like ankylosing spondylitis or psoriatic arthritis with convincing success. In particular, clinical trials testing anti-TNF alpha agents either alone or in combination with MTX have proven the feasibility and efficacy of these novel approaches.