益赛普治疗强直性脊柱炎的临床疗效观察

目的观察益赛普治疗强直性脊柱炎（AS）的临床疗效。方法符合AS诊断标准并处于活动期的患者45例采用完全随机设计方法分为治疗组和对照组，对照组22例给予传统治疗药物及对症治疗，疗程半年；治疗组23例在对照组治疗方案的基础上，前2个月给予益赛普，25mg／次，2次／周。治疗前、后主要观察指标包括活动性指数、功能性指数，晨僵时间、全身和脊柱疼痛程度等，次要观察指标包括扩胸度、枕壁距、Schober试验，血沉、C-反应蛋白及用药安全情况等。结果治疗组除2例经济困难未坚持治疗、1例出现下呼吸道感染而停止治疗外，余20例患者治疗半年后，多个主要观察指标中均有不同程度的改进，脊柱疼痛、晨僵时间均有明显的改善与好转，且疗效优于对照组（P〈0．05），总有效率90．0％。结论对于患有活动性强直性脊柱炎患者，在传统治疗药物基础上加用益赛普，能迅速减轻AS的症状和体征，并可改善AS患者的功能、活动范围和生活质量。     

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.     

Olanzapine: new indication. New indication in acute mania: just another neuroleptic

(1) Lithium is the first-line treatment for patients with acute mania. For patients with psychosis or intense agitation, an oral neuroleptic can be added (haloperidol or chlorpromazine, the best-assessed drugs of this class). (2) The licensed indications for oral olanzapine, a neuroleptic, explicitly mention the treatment of acute mania. (3) The clinical evaluation dossier on olanzapine in this setting (10 mg to 15 mg/day) is not particularly impressive. In particular, clinical trials included patients with a variety of associated psychotic symptoms. (4) The only comparative trial against another neuroleptic, haloperidol at a high starting dose (10 mg), showed that olanzapine was no more effective. The same applies to a trial comparing olanzapine with disodium valproate. (5) One placebo-controlled trial tested olanzapine as an additional treatment in patients who did not respond adequately to lithium or valproate disodium. Olanzapine potentiated the antimanic effects of the original treatment but also increased the incidence of adverse effects. (6) In patients with acute mania, the main adverse effects of olanzapine are drowsiness, weight gain, dizziness, and dry mouth. In the trial comparing olanzapine with haloperidol, olanzapine caused fewer extrapyramidal side effects but more weight gain than haloperidol. (7) Olanzapine costs 20 times more than haloperidol in France. (8) In practice, olanzapine is just another neuroleptic approved for the treatment of acute mania in patients with psychotic symptoms and agitation. There is no evidence that olanzapine has the best risk-benefit ratio in this category.     

依那西普不同用药方案治疗强直性脊柱炎疗效比较

目的观察不同用药方案依那西普[重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白,rhTNFR-Fc]治疗强直性脊柱炎(AS)患者的情况,并比较其不同的临床疗效。方法20例患者随机分成两组,分别给予25mg/次,2次/周和50mg/次,1次/周,连续给药8次,在不同时间点评价ASAS20、ASAS50、BASDAI50等指标。结果两组在第1、4、8次给药及停药后20dASAS20、ASAS50、BASDAI50差异无统计学意义(P>0.05);在总剂量相同(200mg)但是不同用药间隔情况下,25mg组患者与50mg组相比,达到ASAS20、ASAS50、BAS-DAI50改善的例数差异也无统计学意义,但是50mg组较早获得BASFI改善(P=0.0289)。其他指标在不同时间点差异均无统计学意义(P>0.05)。结论不同剂量rhTNFR-Fc、不同间隔时间治疗我国AS患者时疗效差异无统计学意义;50mg,1次/周的方法会给患者带来较早的功能方面(BASFI)的改善;50mg,1次/周给药更方便、经济。     

Infliximab: new indication. Psoriatic arthritis: just another intravenous me-too drug

Minimal assessment, based on a non comparative prospective cohort study of single-agent therapy.     

Etanercept: a review of its use in the management of ankylosing spondylitis and psoriatic arthritis

Etanercept (Enbrel), a recombinant, dimeric, soluble tumour necrosis factor (TNF) receptor protein, is approved in various countries for the treatment of adult patients with ankylosing spondylitis or psoriatic arthritis.Monotherapy with subcutaneous etanercept 25mg twice weekly or 50mg once weekly was effective and generally well tolerated in patients with ankylosing spondylitis or psoriatic arthritis participating in several large, well designed clinical studies. Treatment with etanercept was more effective than placebo in reducing disease activity and improving health-related quality of life (HR-QOL) in both patient populations, and in delaying structural disease progression in patients with psoriatic arthritis. The beneficial response to etanercept achieved with shorter-term treatment was sustained in studies of up to 4 years' total duration. Randomised, well designed, head-to-head comparisons, including pharmacoeconomic analyses, with other anti-TNF biological modulators are required to accurately position etanercept and fully establish its cost effectiveness. In the meantime, etanercept is a valuable treatment option for patients with ankylosing spondylitis or psoriatic arthritis who are suitable candidates for therapy.     

Alclofenac in ankylosing spondylitis.

Eighteen patients with definite ankylosing spondylitis were treated with 3 to 4 g. alclofenac daily for up to 8 months in an open trial against previous therapy. Therapeutic efficacy was greater than or equivalent to previous therapy in 10 of 18 patients after 1 month and 8 patients remain on alclofenac. There was a significant increase in symptoms, particularly morning stiffness after 1 month, but they tended to improve with time. Measurement of spinal movements was not found useful. Side-effects were commoner than expected but not serious. Alclofenac may prove a useful alternative drug in the management of ankylosing spondylitis and further trials are indicated.     

Infliximab: in ankylosing spondylitis

Infliximab is a monoclonal antibody that binds to tumour necrosis factor-alpha and blocks its biological activity. It is approved for use in patients with rheumatoid arthritis, Crohn's disease and ankylosing spondylitis.black triangle In well designed, placebo-controlled trials of 12 or 24 weeks' duration in patients with active ankylosing spondylitis, more infliximab 5 mg/kg recipients achieved a response than placebo recipients according to Ankylosing Spondylitis Assessment Study 20% (61.2% vs 19.2%) or Bath Ankylosing Spondylitis Disease Activity Index 50% (53% vs 9%) criteria (primary endpoints). black triangle Infliximab was also superior to placebo in terms of various secondary clinical endpoints and in reducing spinal inflammation (as assessed by magnetic resonance imaging).black triangle Prolonged efficacy has been demonstrated in patients with ankylosing spondylitis who received infliximab for up to 3 years.black triangle Infliximab is generally well tolerated in patients with ankylosing spondylitis, with most adverse events being of mild-to-moderate severity.     

Modafinil: new indication. For a minority of patients with sleep apnoea

(1) The first-line treatment for patients with troublesome obstructive sleep apnoea syndrome is night-time nasal continuous positive airway pressure, which reduces daytime drowsiness and improves cognitive performance. (2) Modafinil, a non amphetamine psychostimulant already marketed for idiopathic narcolepsy and hypersomnia, is the first drug to be approved in France for the treatment of patients with residual daytime drowsiness despite nasal continuous positive airway pressure treatment. (3) Clinical evaluation of modafinil for this indication consists of two short-term double-blind placebo-controlled trials, lasting 4 and 12 weeks, and including a total of about 500 patients. At a dose of 400 mg/day, 68% of patients experienced an improvement in their daytime drowsiness (usually partial), compared to 37% of patients on placebo. It is not known how many patients no longer had any daytime drowsiness. A major improvement occurred in about 14% of patients (7% on placebo). (4) The main adverse effects of modafinil are neuropsychological (headache, nervousness, insomnia, anxiety, nausea). (5) In short, modafinil is an option to consider when continuous positive airway pressure is not sufficiently effective and when drowsiness continues to significantly interfere with daily activities. However, it only appears to provide a major benefit to about 10% of patients. The only important improvement is in daytime drowsiness, and this is often offset by adverse effects such as headache. Effects of long-term treatment are not known.     

Imatinib: new indication. Chronic myeloid leukaemia, first-line option: favourable findings to be confirmed

(1) For many years the reference first-line treatment for patients with chronic myeloid leukaemia who do not qualify for bone marrow transplantation was interferon alfa-2, possibly combined with cytarabine. (2) Imatinib, a tyrosine kinase inhibitor, was initially approved for second-line treatment of adults with chronic myeloid leukaemia and in the accelerated phase or blast crisis. This indication has now been extended to cover first-line treatment and children. (3) An unblinded trial in 1106 adults compared imatinib (400 mg/day by mouth) as a first-line treatment with the combination of interferon (5 MIU/m2/day) and cytarabine (20 mg/m2/day, 10 days a month) subcutaneously. After 18 months, imatinib significantly increased progression-free survival rate (92.1% versus 73.5%) and quality of survival, but not overall survival. (4) In the paediatric setting, there are follow-up data from only 17 children who received imatinib as a first- or second-line treatment. The results were similar to those obtained in adults. (5) In the only available trial in adults, the number of treatment withdrawals for adverse events was lower among patients taking imatinib. Fatigue and depression were the two serious adverse events reported more commonly by people taking interferon + cytarabine. (6) Imatinib is given by mouth, which is more convenient than subcutaneous route required for interferon + cytarabine. (7) In practice, pending a second comparative trial and further follow-up, imatinib seems a therapeutic advance in the first-line treatment of chronic myeloid leukaemia.     

An overview of investigational new drugs for treating ankylosing spondylitis

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic condition. Pharmacological treatment relies on nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (in case of peripheral involvement) and anti-TNF agents in case of inadequate response. To date, there are no alternate options, and about 30% of the patients do not adequately respond to anti-TNF therapy.

Areas covered: This overview is based on recent publications and programmed studies. The author provides the reader with an overview of AS, its current management and provide details of novel insights into the disorder. From there, the authors highlight novel treatments under investigation before providing their expert opinion on the field.

Expert opinion: The first results with biodrugs targeting the IL-23/Th17 pathway are encouraging, and secukinumab will likely be available in the forthcoming years to treat AS. Other targets may be evaluated in this axis. The author believes that additional head-to-head studies are needed find the place of these new drugs in AS treatment strategies. Further studies are also needed to better evaluate their long-term outcome and safety.     

Rheumatoid arthritis and ankylosing spondylitis occurring together.

Rheumatoid arthritis and ankylosing spondylitis are often difficult to differentiate, though it is important to do so as the natural history and treatment of the two conditions differ. Nine patients have recently been seen, each of whom fulfilled the criteria for both rheumatoid arthritis and ankylosing spondylitis. In eight of the nine patients the histocompatibility antigen HLA-27 was present. A possible explanation of these cases is that one of the diseases occurred by chance in patients already suffering from the other, but this is extremely unlikely. If a chance association is not the correct explanation the basic concepts defining rheumatoid arthritis and ankylosing spondylitis must be reconsidered.