Once-weekly administration of high-dosage Etanercept in patients with plaque psoriasis: results of a pilot experience (power study)

Etanercept is a soluble tumour necrosis factor receptor fusion protein which is approved for the treatment of plaque psoriasis at the dose of either 25mg twice weekly (BIW) or, for the initial 12 weeks, 50mg BIW. Alternative dosing regimens have not been evaluated in psoriasis. In this study, we compare the efficacy and tolerability of two etanercept dosing regimens--50mg BIW and 100mg once weekly (OW)--for 12 weeks in 108 patients with moderate-to-severe recalcitrant psoriasis. Efficacy measures included Psoriasis Area and Severity Index (PASI), severity of pruritus recorded on a visual analogue scale (VAS) and the influence on quality of life assessed by means of Dermatology Life Quality Index (DLQI). Both etanercept regimens caused a significant change in all the efficacy parameters after 4 weeks and 12 weeks, at a comparable rate. At week 12, a PASI improvement of at least 50% from baseline (PASI 50) was achieved by 74% of patients treated with 50mg BIW and 78% of patients treated with 100mg OW. A PASI 75 response was obtained in 54% and 50% of patients treated with 50mg BIW and 100mg OW, respectively. Treatment was well tolerated with similar type and frequency of adverse events between the two groups.     

Serum cytokines and bioumoral immunological characterization of psoriatic patients in long term etanercept treatment

The purpose of this study is to evaluate blood cytokines and immunological parameters in psoriatic patients during long-term treatment with Etanercept. Forty-five subjects of both sexes affected by psoriasis with or without arthritis entered the study and were treated with Etanercept according to international standard protocols. Biochemical blood analysis was carried out at baseline and during follow-up every second month. In particular, the following parameters were kept under control: antinuclear antibodies, anti-nDNA antibodies, anti-histone antibodies, blood cell count, circulating lymphocyte subtypes (CD3, CD4, CD8, CD16, CD19) and IgE. Cytokine profiles (IL-1-alpha, IL-1-beta, IL-6, IL-8, IL-10, IL-12, INF, TNF-alpha) were also evaluated in blood samples during the treatment up to 1 year of follow-up. A significant decrease in PASI score (p < 0.01) and in several cytokine levels was observed, particularly in IL-1, IL-6, IFN-gamma (p < 0.01) and to a lesser extent in TNF-alpha (p < 0.05). No statistically significant changes were recorded after 1 year of follow-up in blood immunological parameters, in particular in ANA titre, CD4/CD8 ratio, IgE levels, CD16, CD19 and eosinophils count. In conclusion, long-term treatment with Etanercept leads not only to a significant improvement in PASI score, but also to significant changes (reduction) in several proinflammatory and modulatory cytokines involved in the pathogenesis of the disease; on the other hand, there are no effects on immunological or bioumoral parameters showing that etanercept modulates rather than suppresses the physiological responses during psoriasis treatment.     

益赛普、柳氮磺砒碇治疗强直性脊柱炎对照研究

目的 通过与柳氮磺砒啶（SSZ）进行对照,研究益赛普对强直性脊柱炎（AS）的疗效.方法 选取处于活动期的AS患者40例,分别给予益赛普（50 mg/周）及柳氮磺砒碇（2.0g/日）进行治疗,总疗程为24周,对两药在12、24周时疗效及观察指标进行评估.结果 益赛普在12、24周时的有效率分别为90.0%,95.0%,柳氮磺吡啶都为70.0%.显示益赛普能显著改善临床实验观察指标（P〈0.05）,耐受性与柳氮磺吡啶差异无显著性（P〉0.5）. 结论益赛普是一种新型有效且安全的治疗AS的药物.     

Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes

BACKGROUND: Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder. Etanercept and narrow-band ultraviolet light B (NB-UVB) are widely used to treat this disease. OBJECTIVE: To evaluate the effectiveness, tolerability, and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis. METHODS: This 12-week, single-arm, open-label study evaluated the combination of etanercept 50 mg twice weekly and NB-UVB thrice weekly in 86 patients. The primary outcome measure was > or =75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75). Other measures included PASI 90, PASI 100, and the Dermatology Life Quality Index (DLQI). RESULTS: At week 12, 26.0% achieved PASI 100, 58.1% achieved PASI 90, and 84.9% of patients achieved PASI 75. Mean improvement from baseline in DLQI was 84.4%. No unexpected, untoward adverse events were noted. CONCLUSIONS: A 12-week course of etanercept plus NB-UVB phototherapy was well tolerated and produced clinically meaningful improvements in signs and symptoms of moderate to severe plaque psoriasis and in patient-reported outcomes. Further investigation of the safety and efficacy of the use of such combination for this indication in controlled clinical trials would be of interest.     

Absence of a clinically relevant interaction between etanercept and digoxin

Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr), is effective and well tolerated in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between digoxin and etanercept at steady state. In a crossover, open-label, nonrandomized, 3-period study, 12 healthy male subjects received loading oral doses of digoxin 0.5 mg every 12 hours on day 1 and 0.25 mg every 12 hours on day 2, followed by a daily maintenance dose of 0.25 mg for a total of 27 days. Etanercept was administered as a twice-weekly 25-mg subcutaneous dose beginning on day 9 and continuing up to day 37 for a total of 9 doses. All ratios of maximum plasma concentration (C(max)) and area under the plasma concentration versus time curve (AUC) for pharmacokinetics of digoxin fell within the confidence interval of 0.8 to 1.25. Although not considered clinically relevant, the mean C(max) and AUC of etanercept were 4.2% and 12.5% lower, respectively, when etanercept was given with digoxin than when administered alone. There were no clinically relevant changes in the electrocardiogram (ECG) parameters, and adverse events did not increase when both drugs were combined. In conclusion, there is no clinically relevant interaction between etanercept and digoxin, and both drugs can be safely coadministered without the need for a dosage adjustment.     

Etanercept: long-term clinical experience in rheumatoid arthritis and other arthritis

Etanercept is a dimeric fusion protein based on the p75 TNF-alpha receptor. It binds to TNF-alpha and blocks its biologic activity. In randomized, double-blind, placebo-controlled trials, etanercept has therapeutic activity in rheumatoid arthritis, psoriatic arthritis, polyarticular-course juvenile idiopathic arthritis and ankylosing spondylitis. Etanercept improves joint inflammation, physical function and slows/halts structural damage, especially when combined with methotrexate. A sustained response is observed in a substantial percentage of patients. Although some safety issues should be considered before starting etanercept treatment, in general terms, etanercept is a well tolerated drug with an acceptable safety profile. The use of any TNF-alpha antagonist must be in agreement with the National Recommendations for Biologic Therapy, and in difficult clinical situations, a balance between risk/benefit needs to be obtained.     

Etanercept: an updated review of its use in rheumatoid arthritis,psoriatic arthritis and juvenile rheumatoid arthritis

Etanercept is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59 to 75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11 to 14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a >or=30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗强直性脊柱炎的临床研究

目的评价重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白益赛普治疗强直性脊柱炎的疗效和安全性。方法应用益赛普治疗6例诊断为强直性脊柱炎的患者,剂量为50mg/次,皮下注射,每周1次,总疗程为12周,治疗前后对每位患者进行临床症状和体征以及实验室检查的评估。结果益赛普治疗后,BASDAI、BASFI、脊柱痛与夜间痛症状以及指地距与治疗前相比具有统计学意义（P〈0.05）。益赛普治疗后,患者的ESR和CRP这两项炎性指标较前均显著下降,其结果具有统计学意义（P〈0.05）,治疗期间未出现严重不良反应。结论益赛普治疗强直性脊柱炎有显著疗效,且具有良好的安全性。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白靶向治疗类风湿关节炎的临床疗效观察

目的观察重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)联合甲氨蝶呤(MTX)治疗类风湿关节炎的临床疗效观察及安全性。方法类风湿关节炎患者60例,随机分为两组。实验组30例,给予每周两次益赛普25mg注射,联合甲氨蝶呤(MTX)治疗12周;对照组30例,单用MTX治疗12周。结果实验组有效率96.7%,对照组有效率66.7%,实验组与对照组比较差异有统计学意义(P<0.05)。实验组在改善临床症状指标方面明显优于对照组(P<0.05),两组不良反应发生率比较无显著统计学意义。结论益赛普联合MTX治疗与单用MTX相比可明显改善类风湿关节炎临床症状和实验室指标,起效迅速,疗效显著,且不良反应无明显增加。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对强直性脊柱炎外周血细胞的影响

目的评价重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(商品名:益赛普)治疗强直性脊柱炎(AS)对患者外周血细胞的影响。方法本研究前6周为随机、双盲、安慰剂对照临床试验,52例AS患者随机接受6周的每周2次益赛普(25 mg)或安慰剂皮下注射;后6周均接受益赛普治疗,于第0、1、2、4、6、7、8、10、12周进行血常规检查及临床疗效评价,分析白细胞总数、中性粒细胞、淋巴细胞、血红蛋白和血小板的变化规律。结果益赛普治疗后第1周,AS患者外周血白细胞总数即较基线时下降(P<0.05),并且有11例患者出现白细胞减少,进一步分析显示益赛普治疗使AS患者中性粒细胞减少、淋巴细胞增多、中性粒细胞减少的程度要高于淋巴细胞增加的程度。临床分析表明白细胞减少与益赛普的疗效无关。同时还发现益赛普治疗可改善AS患者的贫血状态,降低异常升高的血小板。结论益赛普治疗AS在一定程度上可引起患者血液系统的变化,有必要在今后的治疗过程中定期监测血常规。     

青霉胺和低剂量糖皮质激素联合依那西普治疗类风湿性关节炎的疗效观察

目的:观察青霉胺和低剂量糖皮质激素联合依那西普(ETA)治疗类风湿性关节炎(RA)的有效性和安全性。方法:将收集的56例活动性RA患者随机分成2组,对照组28例每日口服青霉胺300mg+泼尼松10mg,qd,4周后减量为5mg;试验组在对照组的基础上联合使用ETA,每周皮下注射2次,每次25mg。疗程均为3个月。疗效采用美国风湿病学会(ACR)标准评定。结果:治疗6、12周后,对照组与试验组的实验室指标和临床症状均有改善,ACR20%改善标准(ACR20)有效率分别为21.4%和46.4%、39.3%和64.3%(P<0.05),进一步比较2组治疗前后简明疾病活动评分(DAS28)的变化,发现与治疗前比较,试验组患者DAS28在6周时已出现明显下降(P<0.05)。试验组的不良反应主要是注射部位反应、上呼吸道感染和胃肠道反应;对照组主要为皮疹反应。结论:青霉胺和低剂量糖皮质激素联合依那西普治疗RA安全、有效,且缓解病情时间更短。     

Etanercept: new indication. For ankylosing spondylitis: another option

(1) Nonsteroidal antiinflammatory drugs (NSAIDs) are the standard drug treatments in ankylosing spondylitis. Infliximab, a TNF-alpha antagonist immunosuppressant, is reserved for severely ill patients for whom standard treatment has failed. Infliximab is provided as an infusion and requires close monitoring. (2) Etanercept, another TNF-alpha antagonist immunosuppressant, was recently approved in Europe for the treatment of ankylosing spondylitis. (3) In three double-blind placebo-controlled trials (40 patients treated for 4 months, 277 patients treated for 6 months, 84 patients treated for 3 months), between 60% and 80% of patients on etanercept "responded" to treatment, with at least a 20% improvement in an endpoint combining various symptoms of ankylosing spondylitis. There are no direct comparisons to show whether this short-term effect differs tangibly from that of infliximab. (4) Etanercept has the same adverse effect profile as infliximab. In particular, both immunosuppressants increase the risk of tuberculosis and opportunistic infections. Risks associated with long-term immunosuppression, such as malignancy, are poorly understood: postmarketing follow-up data are only available for 6 years. (5) As of 7 December 2004, no detailed results had been published on randomised trials comparing etanercept with other recently approved immunosuppressants used to treat ankylosing spondylitis. (6) Etanercept is administered subcutaneously twice a week, on an outpatient basis, for the treatment of ankylosing spondylitis as well as psoriatic rheumatism. In contrast, infliximab is infused every 6 to 8 weeks and must be administered in hospital. (7) Etanercept is an alternative to infliximab as a treatment option for patients with ankylosing spondylitis who have failed to respond to standard treatments.     

Adalimumab: new preparation. Rheumatoid arthritis: no therapeutic advance

(1) There is no agreed treatment for patients with rheumatoid arthritis in whom first-line options, including methotrexate, have failed. Recent slow-acting antirheumatic drugs have not been compared with one another, but they seem to have similar risk-benefit ratios. Etanercept, a TNF-alpha antagonist, is the most convenient to use. (2) Adalimumab is the third TNF-alpha antagonist to be marketed in France for use in rheumatoid arthritis, after etanercept and infliximab. (3) The clinical evaluation dossier mentions no data from comparative trials with other slow-acting antirheumatic drugs used in refractory rheumatoid arthritis. (4) Placebo-controlled trials show that adalimumab alone has very modest efficacy. The best results are obtained when adalimumab is combined with methotrexate. On the basis of the least demanding criterion (ACR 20%), about two-third of patients are improved by this combination. (5) Clinical trials show that it is pointless to continue treatment with adalimumab for more than three months if efficacy is inadequate. (6) Adalimumab, like other TNF-alpha antagonists, can have potentially serious adverse effects, linked mainly to its immunosuppressive action. Opportunistic infections and cases of tuberculosis have been reported, even during short treatment periods. Many questions remain regarding long-term treatment effects, such as the risk of lymphoma, autoimmune disorders, and onset or aggravation of demyelinising diseases. (7) Adalimumab is given once every two weeks, subcutaneously, while etanercept 25 mg is given as two subcutaneous injections per week, and infliximab is given as an intravenous infusion every 8 weeks. (8) In practice, for patients with rheumatoid arthritis who do not respond to methotrexate and to other classical slow-acting antirheumatic drugs, etanercept is the best choice among recent slow-acting antirheumatic drugs.     

Treatment of psoriasis with different dosage regimens of etanercept: preliminary results from the Tαranta Plastic Study Group

This pilot open-label study is aimed to assess clinical response in psoriasis patients receiving diverse dose regimens of etanercept, consisting of the same global cumulative dose of etanercept administered over different treatment periods. Eligible patients were assigned sequentially in a 1:1 ratio to receive: etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) for 12 weeks. The final analysis included a total of 72 patients. At week 12 the Psoriasis Area and Severity Index (PASI) and Skindex-29 scores notably improved in both treatment arms, without significant differences between the two groups. The rate of patients attaining a PASI improvement >or= 50% (PASI 50) at week 12 was 92% in the high-dose group. In these patients, etanercept dosage was decreased to 50 mg QW from week 13, with persistence of the PASI 50 response at week 24 in all cases. Thereafter, treatment was discontinued up to week 36 and almost 30 % of patients experienced a gradual relapse of their psoriasis within this period. In the low-dose group, the PASI 50 response was observed in 75% of patients. These responders continued to be treated with etanercept 50 mg QW up to week 36 with persistence of the PASI 50 in 100% of cases at week 24 and 93% at week 36. In the low-dose regimen, 8 patients who did not respond at week 12 underwent dose escalation to 50 mg BIW for a further 12 weeks. At week 24, six of these patients gained the PASI 50 response, 4 of whom maintained the response up to week 36, after treatment discontinuation from week 24. Our results confirm that etanercept is very effective and well-tolerated in psoriasis and that the drug dosages and treatment duration may be modulated and adapted to clinical needs in a flexible way.     

Etanercept in psoriasis: the evidence of its therapeutic impact

INTRODUCTION: Psoriasis is a chronic inflammatory skin condition for which there is no cure. Treatment options are designed to control the disease symptoms and improve patients' quality of life, and physical and mental function. Established treatments can be effective but are also limited by tolerability, convenience, cosmetic, and economic issues. Etanercept, a fully human soluble tumor necrosis factor (TNF) receptor protein, is a recently approved systemic treatment for chronic moderate to severe plaque psoriasis. AIM: To evaluate the evidence for the therapeutic value of etanercept in psoriasis. EVIDENCE REVIEW: There is clear evidence that etanercept 25 mg or 50 mg twice per week reduces physician-assessed severity of psoriasis and can lead to clearing when compared with placebo. There is substantial evidence that etanercept improves patients' quality of life as determined by both disease-specific and generic instruments. Emerging evidence includes improvements in symptoms associated with depression and fatigue. The tolerability of etanercept in patients with psoriasis appears to be similar to placebo. Initial indications from clinical trials suggest that there is no increased risk of infection or malignancy in etanercept-treated patients with psoriasis. The most common adverse events are reversible injection site reactions. Economic evidence is at present limited, although intermittent etanercept 25 mg is considered cost effective in patients with severe disease unsuitable for systemic treatment. CLINICAL VALUE: Etanercept is an effective and efficient treatment for patients with moderate to severe psoriasis that may be suitable for intermittent use.     

依那西普治疗强直性脊柱炎的安全性研究

目的：观察依那西普治疗强直性脊柱炎（ankylosing spondylitis，AS）出现的不良反应。方法：本研究采用随机、双盲、安慰剂平行对照的方案，2005年4月至2006年1月对52例活动性AS患者随机分入依那西普组及安慰剂组，每组患者各26例，依那西普组平均年龄（27．7±8．5）岁，安慰剂组平均年龄（29．7±8．1）岁。整个研究持续12周，前6周为双盲治疗期，后6周为开放治疗期。在双盲期，依那西普组给予依那西普25mg／次，皮下注射，每周2次，连续用药6周；安慰剂组给予非活性物质25mg／次，皮下注射，每周2次，连续用药6周。开放治疗期，2组均使用依那西普25mg／次，皮下注射，每周2次，连续用药6周。于第0、1、2、4、6、7、8、10、12周进行血常规检查，观察分析注射部位皮肤反应、其他的皮肤及附属器官的反应、感染的发生情况、血液系统反应、肝酶水平、自身抗体反应及其他不良反应。结果：依那西普组和安慰剂组的不良反应发生率分别为23％和38％。差异无统计学意义（P〉0．05）；无严重不良事件发生。双盲期内依那西普组有26．9％的患者出现注射部位皮肤红肿、硬结和瘙痒反应，安慰剂组无l例出现该反应，2组差别有统计学意义（P〈0．05）。试验期间注射部位皮肤反应的发生率为34．6％。双盲期依那西普组有6例患者（23．1％）出现中性粒细胞减少，而安慰剂组无1例发生该反应，2组之间差异有统计学意义（P〈0．05）。依那西普组和安慰组的其他不良反应如上呼吸道感染（分别为5例与7例）、皮肤及附属器官反应（分别为6例和3例）、肝酶升高（分别为5例和8例）等，差异均无统计学意义（均P〉0．05）。结论：依那西普是一种较为安全的治疗AS的药物。     

Efficacy of a timed-release antihistamine/decongestant tablet for symptoms of nasal allergy

In a double-blind study, a timed-release tablet containing carbinoxamine maleate 8 mg and pseudoephedrine hydrochloride 120 mg was compared with placebo for the treatment of signs and symptoms of nasal allergy. Ninety-four adults with rhinitis caused by grass or ragweed allergy were paired according to severity of symptoms and nasal congestion, then assigned randomly to drug or placebo. After baseline measurements were taken, three doses of drug or placebo were given at 12-hour intervals. The active drug was significantly better than placebo in relieving the following symptoms: nasal congestion, nose blowing, sneezing, nasal pruritus, rhinorrhea, ophthalmic pruritus, and sniffles. Improvement over baseline in mean total nasal air flow also was greater in subjects given active drug. The incidence of nonspecific symptoms, including possible drug side effects, was similar between groups. We conclude that the timed-release tablet is safe and effective therapy for the treatment of signs and symptoms of nasal allergy.     

Flumecinol for the treatment of pruritus associated with primary biliarg cirrhosis

Objective: To determine whether flumecinol (3-trifluoromethyl-α-ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis. Methods and Results: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7–day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (X²= 1.24, P= 0.2 7). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95 % confidence interval (CI) –2.1 to 20.81 and for VAS quality of life was 5.0 (95% C1 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 19 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P= 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95 % CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95 % C1 – 5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side-effects. Conclusion: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.     

Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats

BACKGROUND AND PURPOSE: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis. EXPERIMENTAL APPROACH: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature. KEY RESULTS: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression). CONCLUSIONS AND IMPLICATIONS: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.     

Etanercept: new preparation. Useful after methotrexate failure in inflammatory rheumatism

There is no reference second-line treatment for patients with rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthropathy or ankylosing spondylitis after failure or intolerance of a slow-acting antirheumatic drug such as methotrexate. Etanercept, a immunosuppressant targeting TNF-alpha (like infliximab), is now approved in France for use in these situations, with the exception of spondylitis. In the second-line treatment of adults with rheumatoid arthritis, the clinical evaluation dossier on etanercept contains data from dose-finding studies and two placebo-controlled trials involving patients in whom several single-agent treatments had failed. At a dose of 25 mg subcutaneously twice a week, etanercept worked partially in about half the patients. Without direct comparisons, the place of etanercept relative to other slow-acting antirheumatic drugs is difficult to establish. From indirect comparisons, etanercept seems a slightly better treatment option than infliximab. In the first-line treatment of rheumatoid arthritis, one trial showed that etanercept worked faster than methotrexate, but there was no significant difference between the two treatments after two years. Little is known about the efficacy of etanercept in patients with juvenile chronic arthritis who do not respond adequately to methotrexate. There are no comparative trials. One double-blind placebo-controlled trial showed that etanercept, when it worked, remained active for at least 7 months. In one trial, etanercept was more effective than placebo in patients with psoriatic arthropathy and ankylosing spondylitis who continued to receive their usual treatment, which included a slow-acting antirheumatic drug in about 50% of cases. More than 50% of patients treated with etanercept have a cutaneous reaction to the injection. These reactions are usually mild or moderate. Active pharmacovigilance is needed, given its mechanism of action, and previous notifications of a wide variety of adverse effects (even though it is sometimes difficult to establish a foolproof link between etanercept and the adverse effect). Long-term studies of large numbers of patients are needed to determine the precise risk of side effects including haematological, infectious, neurological, oncological and immunological effects. In practice, methotrexate remains the first-line treatment for inflammatory arthritis. Etanercept can be a useful second-line treatment, especially in juvenile chronic arthritis.