Radner Helga, Ramiro Sofia, Buchbinder Rachelle, Landewé Robert B M, van der Heijde Désirée, Aletaha Daniel
Division of Rheumatology,Department of InternalMedicine 3,MedicalUniversityVienna,Vienna,
Cochrane Database Syst Rev. 2012 Jan 18;1(1):CD008951. doi: 10.1002/14651858.CD008951.pub2.
Even with optimal disease-modifying treatment and good control of disease activity, persistent pain due to structural damage is common in people with inflammatory arthritis and therefore additional treatment for pain might be required. Because comorbidity is highly prevalent in people with inflammatory arthritis, it is important to consider comorbidities such as gastrointestinal or liver diseases in deciding upon optimal pharmacologic pain therapy.
To assess the efficacy and safety of pharmacological pain treatment in patients with inflammatory arthritis who have gastrointestinal or liver comorbidities, or both.
We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies to June 2010. We also searched the 2007-2010 ACR and EULAR abstracts and performed a hand search of reference lists of articles.
All randomised or quasi-randomised controlled trials (RCTs or CCTs) were considered for inclusion for assessment of efficacy. For safety we also considered single arm trials, controlled before-after studies, interrupted time series, cohort and case-control studies, and case series of 10 or more consecutive cases. Pain therapy comprised paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs (tramadol) and neuromodulators (anti-depressants, anticonvulsants and muscle relaxants). The study population comprised adults (>18 years) with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis who had gastrointestinal and/or hepatic comorbid conditions. Outcomes of interest were pain, adverse effects, function and quality of life. Studies that included a mixed population of inflammatory arthritis and other conditions were included only if results for inflammatory arthritis were reported separately.
Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data.
Out of 2869 articles only one single arm open trial was identified that fulfilled our inclusion criteria. This trial assessed the safety and efficacy of naproxen (dosage not specified) in 58 patients with active rheumatoid arthritis and gastrointestinal comorbidities for up to 52 weeks. Thirteen participants (22%) remained on gold therapy, four participants (10%) remained on hydroxychloroquine, 27 (47%) remained on corticosteroids, 12 (21%) remained on salicylates and all participants continued on antacids and bland diet. The presence of faecal occult blood was reported in 1/58 participants tested between weeks 1 to 26 and 2/32 participants tested between weeks 27 to 52. Over the course of the study, seven participants (12.1%) withdrew due to adverse events but of these, only two participants withdrew due to gastrointestinal side effects (abdominal pain n=1, nausea n=1) and no serious adverse events were reported. Noteable, out of 14 studies excluded due to inclusion of mixed population (osteoarthritis or other rheumatic conditions) or intervention already withdrawn, five trials reported higher risk of developing gastrointestinal events in patients with prior gastrointestinal events when treated with NSAIDs.
AUTHORS' CONCLUSIONS: On the basis of the current review, there is scant evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain treatment in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondylarthritis. Based upon additional studies that included a mixed population of participants with a range of rheumatic conditions, NSAIDs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinaI comorbidity as there is consistent evidence that they may be at increased risk.
即使采用了最佳的改善病情治疗方法且疾病活动得到良好控制,炎症性关节炎患者因结构损伤导致的持续性疼痛仍很常见,因此可能需要额外的疼痛治疗。由于炎症性关节炎患者中合并症非常普遍,在决定最佳的药物性疼痛治疗方案时,考虑诸如胃肠道或肝脏疾病等合并症很重要。
评估药物性疼痛治疗对患有胃肠道或肝脏合并症或两者皆有的炎症性关节炎患者的疗效和安全性。
我们检索了MEDLINE、EMBASE和Cochrane CENTRAL数据库,检索截至2010年6月的研究。我们还检索了2007 - 2010年美国风湿病学会(ACR)和欧洲抗风湿病联盟(EULAR)的摘要,并对文章的参考文献列表进行了手工检索。
所有随机或半随机对照试验(RCT或CCT)均被考虑纳入以评估疗效。对于安全性,我们还考虑了单臂试验、前后对照研究、中断时间序列、队列研究和病例对照研究,以及连续10例或更多病例的病例系列。疼痛治疗包括对乙酰氨基酚、非甾体抗炎药(NSAIDs)、阿片类药物、类阿片药物(曲马多)和神经调节剂(抗抑郁药、抗惊厥药和肌肉松弛剂)。研究人群包括患有类风湿关节炎、银屑病关节炎、强直性脊柱炎或其他脊柱关节炎且有胃肠道和/或肝脏合并症的成年人(>18岁)。感兴趣的结局是疼痛、不良反应、功能和生活质量。仅当分别报告炎症性关节炎的结果时,才纳入包括炎症性关节炎和其他疾病混合人群的研究。
两位综述作者独立选择纳入试验,评估偏倚风险并提取数据。
在检索到的2869篇文章中,仅识别出一项符合我们纳入标准的单臂开放试验。该试验评估了萘普生(剂量未明确)对58例患有活动性类风湿关节炎和胃肠道合并症患者长达52周的安全性和疗效。13名参与者(22%)继续接受金制剂治疗,4名参与者(10%)继续接受羟氯喹治疗,27名(47%)继续接受皮质类固醇治疗,12名(21%)继续接受水杨酸盐治疗,所有参与者继续使用抗酸剂并保持清淡饮食。在第1至26周接受检测的58名参与者中有1名、第27至52周接受检测的32名参与者中有2名报告出现粪便潜血。在研究过程中,7名参与者(12.1%)因不良事件退出,但其中只有2名参与者因胃肠道副作用(腹痛1例,恶心1例)退出,且未报告严重不良事件。值得注意的是,在因纳入混合人群(骨关节炎或其他风湿性疾病)或干预措施已被撤回而排除的14项研究中,有5项试验报告,有胃肠道既往事件的患者在接受NSAIDs治疗时发生胃肠道事件的风险更高。
基于当前的综述,几乎没有证据可指导临床医生了解胃肠道或肝脏合并症应如何影响类风湿关节炎、银屑病关节炎、强直性脊柱炎或其他脊柱关节炎患者的疼痛治疗选择。基于纳入一系列风湿性疾病混合人群的其他研究,对于有炎症性关节炎且有胃肠道合并症病史的患者,应谨慎使用NSAIDs,因为有一致的证据表明他们可能风险增加。