萘丁美酮与萘普生治疗类风湿关节炎的对比

目的：比较萘丁美酮与奈普生治疗类风湿关节炎（ＲＡ）疗效。方法：萘丁美酮组４４例，服１．０ｇ，ｑｎ，４ｗｋ，萘普生组３２例，服０．２５ｇ，ｂｉｄ，４ｗｋ，用双盲对照法。前组１２例、后组１０例服药延长至０．５ａ。结果：４ｗｋ总有效率前组为６６％，后组４７％，０．５ａ总有效率前组９２％，后组７０％，但均无统计学差异（Ｐ＞０．０５）。结论：２药对ＲＡ的疗效相似，但不良反应胃烧灼感与水肿，萘丁美酮少于萘普生。     

Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis

Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.     

萘丁美酮对类风湿关节炎患者的临床疗效和安全性观察

目的对比萘丁美酮和双氯芬酸钠治疗类风湿关节炎(RA)的疗效和安全性.方法125例活动性RA患者分为二组,随机口服萘丁美酮或双氯芬酸钠,疗程12周.结果萘丁美酮组的总有效率达92.31%,和双氯芬酸钠组的88.5%相当(P=0.573).萘丁美酮对血沉和CRP具有显著性改善(P＜0.05),优于双氯芬酸钠组.二种药物引起胃肠道症状的种类与频率相似.胃镜结果显示,治疗后胃黏膜积分在萘丁美酮组为0%.结论萘丁美酮具有较好的抗炎和止痛作用,对活动性指标血沉和CRP的改善作用显著优于双氯芬酸钠.经胃镜证实的黏膜损伤在萘丁美酮组显著轻于双氯芬酸钠组.     

尼美舒利治疗类风湿关节炎和骨性关节炎的临床研究

目的：观察国产尼美舒利对类风湿关节炎（ＲＡ）和骨性关节炎（ＯＡ）的疗效和安全性。方法：选取ＲＡ患者５９ 例和ＯＡ患者４４ 例。ｐｏ 尼美舒利片１００ ｍｇ,ｂｉｄ;对照组ｐｏ 布洛芬缓释胶囊３００ｍｇ,ｂｉｄ。治疗时间为４ｗｋ。分别观察治疗前后临床指标和炎性实验指标的变化。结果：尼美舒利治疗ＲＡ４ｗｋ 后,疼痛程度、压痛关节数、关节压痛指数、关节肿胀指数、握力、晨僵时间、血沉均显著改善。对ＲＡ的总有效率为８３．３％ 。治疗ＯＡ４ｗｋ 后,膝关节活动痛、１５ｍ 行走时间、日常活动能力及病人综合评估均有显著改善。对ＯＡ的总有效率为７５．０％ 。其不良反应总发生率为１９．２％ , 以胃肠道反应为常见（９．６％）。尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率与布洛芬相比均无显著性差异。结论：尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率均与布洛芬相当。     

Cardiovascular risk profile of antirheumatic agents in patients with osteoarthritis and rheumatoid arthritis

Several new drugs have become available for the treatment of patients with osteoarthritis and rheumatoid arthritis (RA). These agents include selective cyclooxygenase (COX)-2 inhibitors, leflunomide and anti-tumour necrosis factor (TNF)-alpha antagonists. COX-2 inhibitors have a more favourable gastrointestinal adverse effect profile than conventional non-steroidal anti-inflammatory drugs (NSAIDs). However, the COX-2 inhibitors are also associated with hypertension, oedema and congestive heart failure, the well-known adverse effects of conventional NSAIDs. Patients with treated hypertension should be monitored regularly when conventional NSAIDs or COX-2 inhibitors are administered. At present, there is a considerable debate regarding the risk of cardiovascular events with the COX-2 inhibitors. The available literature gives no unequivocal answers. This matter can only be solved by an appropriate trial assessing the cardiovascular risk of these agents. Patients with RA appear to have an enhanced cardiovascular risk which might be related to an unfavourable lipid profile. Corticosteroids induce hypercholesterolaemia in patients other than those with RA. It was recently shown that total and high-density lipoprotein (HDL) cholesterol were low in patients with RA who had a high disease activity. Contrary to the expectation, combination therapy with prednisolone rapidly improved the atherogenic index (total/HDL cholesterol). Ongoing studies investigating this topic are underway. It is not known to what extent corticosteroids induce hypertension in patients with RA. Hence, we advocate blood pressure control for these patients. A small percentage of patients with RA develop hypertension when taking leflunomide, and no other serious cardiovascular adverse effects have been reported in the literature. Blood pressure monitoring is recommended especially in the first months of treatment. TNFalpha antagonists are contraindicated in patients with RA who have congestive heart failure. No specific cardiovascular adverse effects have been reported with the use of these agents in the non-cardiovascular compromised patient. TNFalpha antagonists are the most powerful anti-inflammatory drugs presently available. As inflammation plays an important role in RA as well as in cardiovascular disease and, in view of the increased cardiovascular risk in RA, it is tempting to expect that suppression of inflammation ultimately will lower the cardiovascular morbidity and mortality in patients with RA.     

Valdecoxib: a review of its use in the management of osteoarthritis, rheumatoid arthritis, dysmenorrhoea and acute pain

Valdecoxib is an orally administered, highly selective cyclo-oxygenase (COX)-2 inhibitor with anti-inflammatory and analgesic properties. In well designed trials, valdecoxib demonstrated efficacy versus placebo in patients with osteoarthritis (OA), rheumatoid arthritis (RA), primary dysmenorrhoea and postoperative pain. Initial results in patients with migraine headache were promising. The efficacy of valdecoxib appears dose dependent up to 40 mg/day. Valdecoxib 10 mg/day was as effective as naproxen and rofecoxib in improving signs and symptoms of OA. The American College of Rheumatology 20% response rate was similar in recipients of valdecoxib, naproxen and diclofenac in patients with RA. In patients with dysmenorrhoea, valdecoxib 20 or 40 mg up to twice daily provided as effective pain relief as naproxen sodium 550 mg twice daily. In acute post-surgical pain, single-dose valdecoxib 40 mg had a rapid onset of action, provided similar analgesia to oxycodone 10 mg plus paracetamol (acetaminophen) 1000 mg and provided a longer time to rescue medication than rofecoxib or oxycodone/paracetamol after oral surgery. Pre-emptive administration of valdecoxib 10-80 mg was particularly effective in dental pain. Valdecoxib had opioid-sparing effects after hip or knee arthroplasty and reduced pain after laparoscopic cholecystectomy. Valdecoxib is generally well tolerated. The incidence of gastroduodenal ulcers was generally lower than with nonselective NSAIDs (i.e. NSAIDs not specifically developed as selective COX-2 inhibitors). With concomitant aspirin, the ulcer rate in valdecoxib recipients increased significantly, but was still lower than that in recipients of aspirin plus nonselective NSAIDs. In conclusion, valdecoxib, a COX-2-selective inhibitor, is as efficacious in pain relief as nonselective NSAIDs, with better gastrointestinal tolerability. It was as effective in RA, OA and primary dysmenorrhoea (the approved indications) as nonselective NSAIDs and as effective as rofecoxib in RA flare. In acute post-surgical pain, valdecoxib provided similar pain relief to oxycodone/paracetamol, had a long duration of action, a rapid onset of analgesia and was opioid-sparing. Valdecoxib provides a valuable alternative in the treatment of chronic arthritis pain and acute pain.     

氯诺昔康治疗类风湿关节炎和骨性关节炎41例

目的:研究氯诺昔康治疗类风湿关节炎和骨性关节炎的疗效及安全性.方法:类风湿关节炎(34例)和骨性关节炎(48例)所致膝关节疼痛患者分别随机双盲分成2组,试验组(n=41)行膝关节腔注射氯诺昔康(8mg,每周1次),对照组(n=41)用安慰剂,疗程为3周.对二药治疗前后的疼痛指数进行比较.结果:试验组和对照组在治疗3周后的平均疼痛指数分别减少31.80和8.20(P＜0.05),显示氯诺昔康对关节炎的疼痛有显著疗效.2组不良事件发生率分别为7.31%和4.87%,均无严重不良事件发生.结论:氯诺昔康对类风湿关节炎和骨性关节炎具有良好的镇痛抗炎作用,且耐受性良好.     

Section 2 Long-term use of fenoprofen in rheumatoid arthritis: the therapeutic ratio

Summary

Two previously reported double-blind trials of fenoprofen in 60 patients with rheumatoid arthritis are reviewed. In a preliminary crossover study, 2.4?g. fenoprofen daily was shown to produce statistically highly significant improvements in pain, morning stiffness, analgesic requirements, grip strength, and articular index, but no significant reduction in joint size.

In a 6-month double-blind study, fenoprofen (2.4?g. daily) proved to be as effective as aspirin (mean daily dose: 4?g.) in relieving rheumatoid arthritis symptoms, with considerably fewer side-effects.     

JAK-STAT inhibitors: Immersing therapeutic approach for management of rheumatoid arthritis

Rheumatoid arthritis is a world leading cause of musculoskeletal disease. With the introduction of biological agents as treatment alternatives the clinical possibilities have grown exponentially. Currently most common Disease-modifying anti-rheumatic drugs (DMARDs) treatment option involves intravenous or subcutaneous injection, and some patients struggle to respond to DMARDs or lose their primary reaction. An oral drug formulation with lowered costs of manufacturing and flexibility for healthcare workers to preferably perform treatment will result in decreased healthcare expenditures and increased medication compliance. The JAK-STAT inhibitors, a new class of small molecules drugs, fulfills these criteria and has recently shown efficacy in rheumatoid arthritis. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical trials. Convincing clinical results suggest that therapeutic inhibition of the JAK proteins can effectively modulate a complex cytokine-driven inflammation.     

Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain

Celecoxib is a cyclo-oxygenase (COX) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX-2 over COX-1. Results of randomised double-blind multicentre studies indicate that celecoxib is superior to placebo and has similar efficacy as conventional nonsteroidal anti-inflammatory drugs (NSAIDs) in improving the signs and symptoms of osteoarthritis and rheumatoid arthritis. Analgesic efficacy and improvements in functional status are apparent within 2 weeks of starting therapy and are maintained throughout treatment. Available data suggest that celecoxib has analgesic efficacy in patients with postsurgical dental pain, although this is yet to be confirmed. In patients with osteoarthritis of the knee, celecoxib 100 and 200 mg and naproxen 500 mg twice daily were similarly efficacious and superior to placebo. Once and twice daily celecoxib dosage regimens provided comparable efficacy. Improvements in physical function paralleled those in pain relief. Celecoxib also has efficacy in treating the signs and symptoms of osteoarthritis of the hip. The effects of celecoxib were not diminished in elderly patients with osteoarthritis of the hip or knee. All dosages of celecoxib (100 to 400 mg twice daily) and naproxen 500 mg twice daily produced significant anti-inflammatory and analgesic effects in patients with active rheumatoid arthritis. In patients with stable rheumatoid arthritis, celecoxib 200 mg twice daily showed sustained symptomatic improvements similar to those of twice daily slow-release diclofenac 75 mg over a 24-week period. Celecoxib was well tolerated in clinical trials. Upper gastrointestinal complications occurred in significantly fewer patients treated with twice daily celecoxib 25 to 400 mg than in those receiving comparator NSAIDs. There was no evidence of a dose relationship in endoscopic ulcer development and incidences in celecoxib and placebo recipients were lower than in those receiving twice daily naproxen 500 mg or ibuprofen 800 mg 3 times daily. Conclusions: Celecoxib is the first COX-2 specific inhibitor approved for use in osteoarthritis and rheumatoid arthritis. Celecoxib produces significant improvements in pain and inflammation and these effects are maintained during treatment for up 24 weeks in clinical trials. Studies indicate that celecoxib has similar efficacy to conventional NSAIDs in relieving pain and improving functional status, but is associated with a lower incidence of upper gastrointestinal ulceration and complications. This promising gastrointestinal safety profile, together with sustained symptomatic relief, places celecoxib as a useful alternative for the treatment of osteoarthritis and rheumatoid arthritis, particularly in patients at high risk of developing gastrointestinal events. Although data are encouraging, its place in acute pain states remains to be established.     

Etanercept: a review of its use in the management of rheumatoid arthritis

Etanercept (Enbrel), a soluble fusion protein that binds specifically to the cytokine human tumour necrosis factor (TNF), is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis in the US, Italy, the rest of the EU and other countries worldwide. Subcutaneous etanercept was efficacious and generally well tolerated in several large, well designed, clinical trials and in the clinical-practice setting in adult patients with rheumatoid arthritis, including methotrexate-naive patients with early disease and those with long-standing, treatment-resistant active disease. Etanercept plus methotrexate combination therapy was generally superior to either monotherapy in reducing disease activity and structural joint damage, as well as improving health-related quality of life (HR-QOL). Furthermore, etanercept monotherapy was superior to placebo and at least as effective as methotrexate therapy in reducing disease activity and improving HR-QOL in patients with early or refractory disease. The beneficial effects of etanercept monotherapy or combination therapy were sustained in the long term (< or =9 years). Some pharmaco-economic analyses suggest that etanercept is a cost-effective option in the treatment of patients with rheumatoid arthritis. Direct head-to-head comparisons with other biological agents would help to definitively position etanercept with respect to these agents. Nevertheless, extensive clinical experience indicates that etanercept is a valuable treatment option in adult patients with long-standing moderate to severe active rheumatoid arthritis and an emerging option in those with early disease.     

Sulfasalazine: a review of its use in the management of rheumatoid arthritis

Sulfasalazine (salazosulfapyridine) [Azulfidine, Salazopyrin] is a well established disease-modifying antirheumatic drug (DMARD) used in the treatment of patients with rheumatoid arthritis. Clinical trials with sulfasalazine have used an array of measures of disease activity, such as the number of tender and swollen joints, Ritchie articular index (RAI) and erythrocyte sedimentation rate (ESR). In randomised, double-blind, placebo-controlled trials, sulfasalazine was associated with statistically significant benefits for various measures of disease activity, according to results of individual trials and/or meta-analysis. Sulfasalazine was associated with broadly similar efficacy to that of various other DMARDs in several randomised, double-blind, comparative trials. Promising results have also been demonstrated with sulfasalazine in combination with other DMARDs (e.g. methotrexate and hydroxychloroquine) in patients with early rheumatoid arthritis and in those with more established disease. Sulfasalazine was generally well tolerated in clinical trials, the most frequently reported adverse effects being adverse gastrointestinal effects, headache, dizziness and rash; myelosuppression can also occur. Sulfasalazine has a relatively short lag time until its onset of action and is often considered to be among the more efficacious traditional DMARDs. Based on considerations of safety, convenience and cost, many rheumatologists (particularly outside of the US) select sulfasalazine as initial therapy, although preferred first-line treatment options vary between countries.     

Infliximab: a review of its use in the management of rheumatoid arthritis

Infliximab is a chimaeric monoclonal antibody to human tumour necrosis factor-alpha (TNFalpha). It binds to both soluble and transmembrane forms of TNFalpha at picomolar concentrations in vitro. Secondary to inhibition of TNFalpha, infliximab reduces serum levels of inflammatory mediators and vascular endothelial growth factor, decreases the expression of chemokines in the synovial tissue and reduces lymphocyte migration into the joints of patients with rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted over 26 and 30 weeks, infliximab plus methotrexate was significantly more effective than placebo plus methotrexate according to American College of Rheumatology response criteria in patients with active rheumatoid arthritis. A substantial response to infliximab-containing regimens was evident within 2 weeks. Extension phases of these studies indicate sustained clinical efficacy for up to 54 weeks. Of considerable importance are preliminary 1-year radiographic findings that show zero median progression of joint damage in infliximab plus methotrexate recipients compared with a 7 to 8% deterioration in placebo plus methotrexate recipients. Headache, nausea, upper respiratory tract infection and infusion-related reactions are the most commonly reported adverse events with infliximab. Serious events occurred in 4.4% of infliximab versus 1.8% of placebo recipients. In the largest clinical trial, 2 patients died from disseminated infection and 3 developed new or recurrent malignancies, although the exact relationship between infliximab and these events is unknown. To date, 2 patients with rheumatoid arthritis have developed drug-induced lupus. About 10% of patients may develop antibodies to infliximab, although the clinical significance of these is presently unknown. Conclusion: Infliximab represents an important advance in the treatment of rheumatoid arthritis, with tolerability concerns raised by early studies having been eased somewhat by more recent data in larger patient numbers. If preliminary results indicating that infliximab is able to arrest joint destruction in patients with rheumatoid arthritis are corroborated, the drug will likely become an integral component of future management strategies for this difficult-to-treat condition.     

Juvenile rheumatoid arthritis: therapeutic perspectives

Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need, especially for pediatric use, to develop agents that can be taken orally. Long-term studies will be required to assess the tolerability and toxicity of these approaches in JRA, since cytokines and other mediators play important roles in host defenses, and the chronic inhibition, exogenous administration or constitutive over-expression of some cytokines/mediators may have undesirable effects.     

The positive effect of pregnancy in rheumatoid arthritis and the use of medications for the management of rheumatoid arthritis during pregnancy

Inflammopharmacology - Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist...     

塞来昔布治疗类风湿关节炎和骨关节炎有效性和安全性的临床研究

目的评价塞来昔布治疗类风湿关节炎(RA)和骨关节炎(OA)的有效性和安全性。方法采用随机、双盲、双模拟和对照研究的方法,将48例患者分为治疗组24例,其中RA14例,OA10例,每天早、晚各服塞来昔布100mg和安慰剂1片;对照组24例,其中RA13例,OA11例,每天早、晚各服双氯芬酸50mg和安慰剂1片,治疗12周以评价药物的安全性和有效性。结果譹两组患者对关节炎疼痛的评估(VAS)均有明显改变;两组差值为3.0,其95%可信区间(CI)为-14.4~20.4;②患者对疾病的总体评价,两组差值为0.1,其95%CI为-0.39~0.59;譻研究者对疾病的总体评价,两组差值为0.05,其95%CI为-0.59~0.49;譼对照组发生胃肠道不良事件3起,治疗组未报告胃肠道不良事件(Fisher精确概率检验,P=0.233)。结论塞来昔布、双氯酚酸均能显著降低患者对关节炎疼痛的评估,改善患者及研究者对疾病状况的总体评价,塞来昔布具有良好耐受性。     

Biologics in development for rheumatoid arthritis: relevance to osteoarthritis

The osteoarthritis disease process affects not only the cartilage but also the entire joint structure, including the synovium, bone and periarticular muscles. Characteristically, abnormal biomechanical forces result in an imbalance between chondrocyte anabolic and catabolic pathways, which ultimately leads to progressive joint destruction. Within cartilage and synovium, pro-inflammatory cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own production and induce chondrocytes to produce additional catabolic mediators, including proteases, chemokines, nitric oxide, and prostaglandins. The success of targeted biological therapy in rheumatoid arthritis has taught that the blockade of a single dominant cytokine can lead to remarkable clinical benefit, even in complex disease. The effectiveness of biologicals in inflammatory arthritides as disease modifying agents has increased the likelihood that similar strategies can be developed to target specific molecular mechanisms in osteoarthritis (OA). However, since the clinical development program for disease-modifying OA drugs (DMOADs) is complicated by the slow progression of disease in many patients, the introduction of DMOADs will be greatly enhanced by advances in imaging and biomarkers that serve as validated surrogate endpoints for meaningful clinical outcomes.