ADVERSE EVENTS IN PATIENTS WITH BLOOD LOSS: A POOLED ANALYSIS OF 51 CLINICAL STUDIES FROM THE CELECOXIB CLINICAL TRIAL DATA BASE

Background: Despite their accepted efficacy, it is well recognized chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of gastrointestinal (GI) toxicity, including overt bleeding, ulceration, occult blood loss, and the development of clinically significant anemia (decreases in hemoglobin ≥2 g/dL). Objectives: To investigate the clinical importance of blood loss in patients in the celecoxib clinical trial data base. Methods: Pooled analysis of 51 blinded, controlled clinical studies ≥4 wks duration comparing celecoxib, a selective cyclooxygenase-2 NSAID, with NSAIDs or placebo. Patients with osteo-/rheumatoid arthritis, ankylosing spondylitis, chronic low back pain, Alzheimer disease and polyps were included; the majority were treated for >6 mths. The adverse event (AE) profile in patients with clinically significant blood loss (defined as decreases in hemoglobin >2 g/dL and/or hematocrit by >10% from baseline) was compared with the AE profile in patients without such blood loss. For the primary analysis, an AE was considered to be associated with blood loss if it occurred at any time during the time window (see below). Comparisons were based on the percentage of patients with AEs and not annualized for the duration of the observation period. In addition, events that occurred in <1% of patients in both groups were excluded from any comparisons. A ≥4-fold difference between groups was defined arbitrarily as being markedly higher. Results: 839 of 51,048 patients experienced defined clinically significant blood loss. Baseline demographics were similar in patients with/without clinically significant blood loss. The incidence of AEs was markedly higher in patients who experienced clinically significant blood loss than those who did not. The majority of these differences were for GI AEs (gastric ulcer, GI hemorrhage, melena) or their likely sequelae (anemia, increase in blood creatinine, decrease in hemoglobin and/or hematocrit) as might be expected following NSAID treatment. However, the incidence of the following non-GI related AEs was also markedly higher in patients with defined clinically significant blood loss compared with patients without such blood loss: coronary artery disease (1.2% vs 0.3%, respectively), myocardial infarction (1.1% vs 0.2%), asthenia (1.3% vs 0.3%), and pneumonia (2.4% vs 0.4%). Withdrawals due to AEs were more common among patients who experienced clinically significant blood loss (18%) than those who did not (10%). Conclusions: Clinically significant blood loss, even when detected only as decreases in hemoglobin >2 g/dL and/or hematocrit by >10% from baseline, may have clinically important adverse consequences beyond the sequelae previously known to be associated with NSAID-related GI effects. References: 1. Chan et al. Lancet. 2010;376:173-79. Disclosure of Interest: G. Sands Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., B. Shell Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Zhang Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.Citation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 602Session: Rheumatoid arthritis – non-biologic treatment (Poster Presentations )