| Summary: | 碩士 === 高雄醫學大學 === 臨床藥學研究所 === 100 === Objectives: To examine the risk of hospitalization for GI adverse events and drug switching events with regard to early discomfort of gastrointestinal (GI) adverse events among users of non-steroidal anti-inflammatory drugs (NSAIDs) with or without co-medication with gastro-protective drugs (GPDs).
Methods: This is a retrospective cohort study. The Taiwan Longitudinal Health Insurance Database (LHID) 2000 during 1997 to 2008 was used to identify patients with newly diagnosis of RA (ICD-9-CM: 714.0~714.3, n=22,968) or OA (ICD-9-CM: 715.0~715.9, n=156,933) in 1998-2007 to allow for at least one follow-up year.
To observe the association of different treatment groups and GI events (or switching events), there were two follow-up designs: the first one was followed by person and the second one was followed by medication intervals of consecutive use. The medical utilization of NSAIDs was classified into three main classes: traditional non-steroidal anti-inflammatory drugs (tNSAIDs), preferential COX-2 selective inhibitors (pC2SIs), and specific COX-2 selective inhibitors (COXIBs) with or without combination with proton pump inhibitors (PPIs).
The study endpoints are the first diagnosis of hospitalization for GI events (ICD-9-CM of upper GI: 530~535,578 or of lower GI: 555, 562, 569) in the first follow-up study, and drug switching to another class of NSAID or GI events (same as the first study) in the second study.
Drug dose dispensed was presented as total amount of defined daily dose (DDD). Statistical analysis, for different treatment groups , we used Kaplan-Meier estimates and the Cox proportional hazards regressions with covariates of patient’s age, gender, prior GI history times, co-medication, and comorbidity score to estimate the hazard ratios (HR) of hospitalization for GI events and drug switching among different treatment groups.
Results: A total of 24,163 newly diagnosis RA patients and 144,041 newly diagnosis OA patients were identified from LHID 2000. A majority (98.70%) of users had been prescribed tNSAID, 53.37% were classified as tNSAID alone and 42.33% as tNSAID augmentation.
Use of tNSAID+COXIB and tNSAID+pC2SI was statistically significantly associated with lower risk of hospitalization for upper GI events when comparing to use of tNSAID alone (HRs=0.78 and 0.70, 95%CI 0.70~0.87 and 0.58-0.85 for patients with prior GI history; HRs=0.83 and 0.81, 95%CI 0.79~0.87 and 0.74~0.88 for patients without prior GI history). However, compared to tNSAID alone, those treatment groups with PPI use and without prior GI history had higher risk of developing GI events (HR=1.21, 95%CI=1.09~1.34 for tNSAID+PPI; HR=0.95, 95%CI= 0.86~1.05 for tNSAID+pC2SI+PPI; HR=1.14, 95%CI = 0.93~1.39 for tNSAID+COXIB+PPI).
There were 890,833 intervals identified from 166,762 patients. A majority of patient-intervals (91.73 %) of consecutive use were prescribed with tNSAID use. Given no prior GI history, patients in the tNSIAD+PPI treatment group was less likely to switch (HR=1.62, 95%CI=1.45~1.81) than tNSAID alone. However, the HRs for switching to COXIB, COXIB+PPI, pC2SI and pC2SI+PPI were 6.75 (95%CI= 6.60~6.89), 6.48 (95%CI= 5.35~7.86), 8.43 (95%CI=8.30~8.56) and 8.81 (95%CI=7.36~10.5) respectively. For the relative risk of GI events comparison, patient-intervals with COXIB or pC2SI alone had significantly lower risk of developing upper GI adverse events (HR= 0.82, 95%CI=0.74-0.92; HR=0.88, 95%CI=0.82-0.95) and had a trend of lower risk for developing lower GI adverse events (HR=0.83, 95%CI =0.55~1.24; HR=0.96, 95%CI= 0.73~1.27).
Conclusions Our results provide that COX-2 selective inhibitors (pC2SI and COXIB) compared to tNSAID have a lower risk to develop GI adverse events. Due to the regimen of tNSAID+PPI was less likely to switch, it could be an acceptable augmentation in clinical practice for reducing potential GI adverse events.
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