Celecoxib, a cyclooxygenase-2 inhibitor, improved upper gastrointestinal lesions in rheumatoid arthritis patients as assessed by endoscopic evaluation

Abstract

We prospectively evaluated the effects of celecoxib (CEL) on the gastrointestinal (GI) tract of rheumatoid arthritis (RA) patients with endoscopically identified GI mucosal injury after therapeutic switching from the long-term use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Upper GI endoscopy was performed on RA patients who had been treated with NSAIDs for ≥3 months. GI mucosal injury was evaluated according to the modified LANZA score. Patients with mucosal injury without ulcers were switched from NSAIDs to CEL, while those with ulcers were switched to CEL with famotidine after ulcer healing. At week 16 of treatment, GI mucosal injury was endoscopically revaluated. An efficacy analysis was performed before therapeutic switching and at 8 and 16 weeks post-switching. Endoscopic analysis revealed GI mucosal injury, including six ulcers, in 45 of the 82 patients (54.9%). Sixteen weeks after switching to CEL, LANZA scores were significantly improved [2.1 ± 0.8 (pre-switching) vs. 1.6 ± 1.3, P = 0.0073] in patients with LANZA scores of 1, 2, or 3 (n = 35). The Disease Activity Score using 28 joint counts (DAS28) [erythrocyte sedimentation rate item score (ESR4) (P = 0.0257) and C-reactive protein item score (CRP4) (P = 0.0031)] was also significantly improved by week 16. Based on these results, we conclude that preexisting NSAID-induced upper GI injury is improved following therapeutic switching to CEL without any reduction in analgesic efficacy.

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

“…This study argues that the celecoxib-induced stomach, liver and brain lesions resulting from extended COX-2 inhibition are a function of NO system dysfunction, which is particularly worsened after a high-dose application. Considering the advanced safety profile of celecoxib[ 10 ], lower celecoxib regimens such as 200 mg/kg and 500 mg/kg given intraperitoneally were without notable effect on gastric, liver or brain lesions (thus, these results are not specifically shown). These lesions could be all influenced by the NOS substrate L-arginine and in particular by the stable pentadecapeptide BPC 157, which is an agent known to counteract non-selective NSAID-induced ulcerogenesis as well as the liver and brain lesions that interact with the NO system[ 1 , 9 ].…”

“…It was previously shown that celecoxib improved gastric lesions[ 10 ], induced the regression of preneoplastic lesions in the liver[ 11 ] and counteracted brain lesions and convulsions[ 12 - 14 ].…”

“…Furthermore, we should emphasize that the previous high-dose regimens used to demonstrate the toxicity of all non-selective NSAIDs[ 5 - 8 ] were compared with μg-ng regimens of BPC 157 as a potential antidote to counteract these effects[ 1 ] and to examine the safety profile of celecoxib. Thus, we consistently used this selective NSAID at very high doses that consequently markedly exceeded the maximal dose used in patients[ 10 ]. Likewise, in rats treated with celecoxib, both BPC 157 regimens, μg and ng, were also validated against the NO-related agents L-NAME and L-arginine, which were given either alone and/or in combination.…”

The prevalence of endoscopic gastric mucosal damage in patients with rheumatoid arthritis

“…And, treatment with COX-2-selective NSAIDs might help resolve this issue in RA patients. It has already been reported that COX-2-selective NSAIDs have a gastric ulcer-protective effect compared with non-selective NSAIDs in RA patients [ 26 , 27 ]. Our present study also demonstrated that the modified LANZA score of RA patients treated with COX-2-selective NSAIDs was lower than that in RA patients treated with non-selective NSAIDs.…”

Implementation of Proton Pump Inhibitor Deprescription Protocol in Geriatric Residents

“…The protocol encouraged use of misoprostol (100 µg once daily) for gastropathy prophylaxis, buffered aspirin (81 mg once daily) for cardiovascular prophylaxis, and celecoxib (200 mg twice daily) for rheumatoid arthritis based on the limited amount of evidence of safety and efficacy. 14-17 Enrolled residents received standard care, guaiac test at baseline and conclusion as well as symptom questionnaire at baseline, every 3 weeks, and at conclusion. Nurses, residents, pharmacists, and physicians were educated about the harms, intents, methods, and duration of the protocol.…”