The use of nonsteroidal anti-inflammatory drugs—including the group of cyclooxygenase-2–specific coxibs—by patients with rheumatoid arthritis did not significantly impact renal function, judging from the results from a large prospective cohort study that was presented June 17 at the annual European Congress of Rheumatology in Rome.

Despite this reassuring finding, Dr. Burkhard Möller recommended that any patients who are scheduled to begin long-term, high-dose NSAID therapy should undergo a baseline assessment of glomerular filtration rate and be monitored thereafter.

“Renal toxicities rank among the best known complications of treatment with NSAIDs,” lead investigator Dr. Möller of Bern (Switzerland) University Hospital said in an interview. “NSAIDs are considered as a major reason or at least a cofactor for hospital admission due to acute renal failure. The statistical risk for acute renal failure is three times higher in patients taking these agents, especially during the first month of NSAID use. Therefore, there exists a well-argued general skepticism against use of NSAIDs, in addition to the known gastrointestinal and cardiovascular risks,” he explained.

Despite all the caveats, he continued, patients with chronic arthritis often require—in addition to disease-modifying treatment—further pain relief via nonnarcotic analgesics, such as NSAIDs.

In the study, Dr. Möller and his associates studied a nested cohort of 2,770 patients who were enrolled in the Swiss RA Registry and had at least two documented glomerular filtration rates (GFRs) according to the Cockroft-Gault formula. The patients were observed for a mean of 3.1 years. Their mean drug-exposure time was 2.5 years to conventional NSAIDs and 0.5 years to coxibs. At the congress, Dr. Möller reported on data from 1,657 patients.

At the start of annual observations, 20% of patients were taking NSAIDs and 18% were taking coxibs. By the end of the observation period, 18% of patients were still taking NSAIDs and 12% were still taking coxibs.

The median annual change in GFR in this most conservative analysis was 1.3 mL/min, and estimates were even less in additional longitudinal analyses for more than 4,000 patients. Neither start nor continuation of the NSAIDs altogether, or of the subgroup of coxibs or nonselective NSAIDs, significantly modified the clearance rates. Furthermore, no single NSAID was associated with worsening of GFR estimates in annual analyses.

“We did not find a dose effect, nor other modifications of renal function by NSAID except for patients with baseline grade IV renal insufficiency (clearance of less than 30 mL/min), which underwent accelerated loss of renal function,” Dr. Möller said.

Only 2% of physicians who treat this cohort of patients reported prevalence of renal comorbidity. However, the researchers found that the true frequency of at least moderate renal insufficiency (defined as chronic kidney disease of stage 3 or higher) was about 18%. “Thus, rheumatologists did not much care about the existent renal condition, and prescribed NSAID irrespective of this objective relative contraindication in two-thirds of the patients,” Dr. Möller noted.

He went on to conclude that NSAIDs “can still be estimated as valuable and safe drugs when used responsively. Many patients can be treated for years without any of the expected complications. If your patient is still suffering from unbearable pain despite appropriate disease-modifying therapy, it might be unethical not to treat him. In this situation, consider NSAIDs after careful evaluation of any potential risk, especially for gastrointestinal, cardiovascular, and renal complications. Measure or estimate the renal function by validated tools before starting NSAIDs. Do not use NSAIDs in [chronic kidney disease] stage 4 or 5, and control the kidney function in stage 3 after having started with NSAID therapy.”

Dr. Möller acknowledged certain limitations of the study, including the fact that it was not randomized and that about one-third of patients were lost during follow-up. Dr. Möller said that he had no relevant conflicts to disclose.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

据6月17日在罗马召开的欧洲风湿病学年会上提交的一项大规模前瞻性队列研究的结果，在类风湿性关节炎患者中应用非类固醇类抗炎药(其中包括环氧化酶2特异性昔布类药物)不会对患者的肾功能造成显著影响。

 

尽管这一结果令人欣慰，Burkhard Möller博士建议所有打算接受长期、高剂量非类固醇类药物(NSAID)治疗的患者均应进行肾小球滤过率基线评估，并在用药后保持监测。

 

 “在应用NSAID类药物治疗所致的并发症中，肾毒性是最知名的几种之一，”该论文的主要研究者，瑞士伯尔尼大学医院的Möller博士在一次受访时说。“NSAID被视作患者因急性肾衰竭入院的主要诱因或(至少也是)一种辅助因素。服用此类药物的患者发生急性肾衰竭的统计学风险要高3倍，尤其是在使用NSAID药物的第一个月。因此，就NSAID类药物而言，除了存在广为人知的胃肠道及心血管风险外，还存在一种论据充分的普遍怀疑态度。

 

他接着说道，尽管存在上述不足，除了需要接受缓解病情的药物外，患有慢性关节炎的患者常常还需要进一步使用非麻醉类镇痛药，如NSAID类药物。

 

在这项研究中，Möller博士及其同事对一项纳入2,770例患者的巢式队列进行了研究，这些患者均由瑞士类风湿关节炎登记处(Swiss RA Registry)招募，且患者档案中至少有2项肾小球滤过率 (GFR)的记录值(均采用Cockroft-Gault公式估算)。患者的平均观察期为3.1年。其应用传统NSAID类药物的平均时间为2.5年，应用昔布类药物的时间为0.5年。Möller博士在会议上对源于1,657例患者的数据进行了报告。

 

在年度观察开始时，正在服用NSAID类和昔布类药物的患者分别占总人数的20%和18%。截至观察期结束时，仍服用NSAID类和昔布类药物的患者分别占总人数的18%和12%。

 

这一最保守分析的结果显示，受试者GFR的年变化中位值为1.3 ml/min，而之后对超过4,000例患者进行纵向分析所得出的估测值则更低。无论是刚开始还是继续使用NSAID类药物，或该药的昔布亚类，或非选择性NSAID类药物，其对患者的肾脏清除率均未造成显著影响。此外，年度分析的结果显示，单独使用任何一种NSAID类单一药物均与GFR估算值降低无关。

 

 “我们发现，应用NSAID类药物并不存在剂量效应关系，其对患者肾功能的其他方面亦无影响，唯一的例外是基线评估分级为IV级肾功能不全(清除率<30 ml/min)的患者，这些患者的肾功能正在加速恶化。” Möller博士说。

 

在这一队列患者的主治医生中仅有2%报告了肾脏共病的患病情况。然而，研究者们发现，约有18%的患者存在至少中度的肾功能不全(定义为慢性肾病3期或更高)。“因此，风湿病学家并未过分关注患者的肾功能现状，并为这些患者开了包含NSAID类药物的处方，尽管其中有2/3的患者客观上存在相关禁忌证，” Möller博士指出。

 

他进一步总结说，NSAID类药物“在针对性用药的前提下，仍应被视作是一种安全而有价值的药物。许多患者即便持续用药数年也并未出现任何预期并发症。如果你的患者在接受缓解病情治疗后仍然存在无法忍受的疼痛，那么，不对他进行治疗可能就是不道德的。在这种情况下，在对患者可能存在的任何风险(尤其是胃肠道、心血管和肾脏的相关并发症)进行仔细评估后，便应该考虑应用NSAID类药物。在开始使用NSAID类药物前应使用验证工具对患者肾功能状况进行测量或评估。不应对慢性肾病4期或5期的患者应用NSAID类药物，且一旦开始使用NSAID治疗，便应该将患者肾功能控制在3期以内。

 

Möller博士承认该研究存在某些不足之处，包括该研究并未遵循随机化设计，且在随访期间有大约1/3的患者失访。Möller博士说他没有相关利益冲突需要披露。

 

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