Miyake Kazumasa, Kusunoki Masanori, Shinji Yoko, Shindo Tomotaka, Kawagoe Tetsuro, Futagami Seiji, Gudis Katya, Tsukui Taku, Nakajima Atsushi, Sakamoto Choitsu
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
J Gastroenterol. 2009;44(2):113-20. doi: 10.1007/s00535-008-2278-2. Epub 2009 Feb 13.
Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment.
This retrospective cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least 3 months. Potential risk factors for endoscopic PU were analyzed in RA outpatients on longterm NSAID treatment.
PU incidence was 31% with bisphosphonate co-therapy and 17% without the co-therapy. PU incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogues (PG) co-therapy, 14% with histamine-H(2) receptor antagonists(H2RA) co-therapy, and 27% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for PU (OR, 2.29; 95% CI, 1.09-4.81). Other risk factors for ulcer development were advanced age (greater than 60 years) and smoking (OR, 2.58; 95% CI, 1.03-6.49 and OR, 2.71; 95% CI, 1.13-5.53, respectively.) Factors that significantly reduced the incidence of PU were H2RA or PPI/PG cotherapies (OR, 0.29; 95% CI, 0.12-0.68.).
Bisphosphonate co-therapy as well as advanced age and smoking was found to be a significant risk factor in PU, while co-therapies of standard-dose H2RA or PPI/PG proved effective in preventing PU in Japanese RA patients on long-term NSAID treatment.
类风湿性关节炎（RA）患者因非甾体抗炎药（NSAIDs）导致消化性溃疡（PU）的风险增加。然而，在日常临床环境中，潜在药物相互作用对PU发生发展的影响尚未确定。目的是评估日本长期接受NSAID治疗的RA门诊患者联合用药出现的对PU具有临床重要意义的相互作用。
这项回顾性队列研究纳入了196例连续接受NSAID治疗至少3个月的RA门诊患者。对长期接受NSAID治疗的RA门诊患者内镜下PU的潜在危险因素进行了分析。
双膦酸盐联合治疗组PU发生率为31%，未联合治疗组为17%。质子泵抑制剂（PPI）或前列腺素E1类似物（PG）联合治疗组PU发生率仅为5%，组胺H2受体拮抗剂（H2RA）联合治疗组为14%，未使用抗溃疡药物组为27%。在多因素逻辑回归分析中，双膦酸盐联合治疗仍然是PU的一个显著危险因素（比值比[OR]，2.29；95%置信区间[CI]，1.09 - 4.81）。溃疡发生的其他危险因素是高龄（大于60岁）和吸烟（OR分别为2.58；95% CI，1.03 - 6.49以及OR为2.71；95% CI，1.13 - 5.53）。显著降低PU发生率的因素是H2RA或PPI/PG联合治疗（OR，0.29；95% CI，0.12 - 0.68）。
双膦酸盐联合治疗以及高龄和吸烟被发现是PU的显著危险因素，而标准剂量H2RA或PPI/PG联合治疗在预防长期接受NSAID治疗的日本RA患者发生PU方面被证明是有效的。
