Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases

Wolfgang W Bolten
Division of Rheumatology, Klaus-Miehlke Klinik, Wiesbaden, Germany

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are successfully used to alleviate pain and inflammation in rheumatic diseases. In an appreciable percentage of cases, the use of systemic NSAIDs is associated with adverse lesions of the gastrointestinal (GI) mucosa up to life-threatening perforations, ulcers, and bleeding. Reliable warning signals mostly do not arise. Therefore, it is important to take preventive measures to reduce the GI risk. One established method is to assign cyclooxygenase 2 (COX-2)-specific inhibitors (coxibs) instead of traditional NSAIDs (tNSAIDs). Coxibs spare in part the endogenous gastroprotective mechanisms. Another reliable choice to improve the GI safety is the comedication of proton pump inhibitors (PPIs) to suppress gastric acid. A fixed NSAID/PPI combination ensures expected protective effects by improving patients’ PPI adherence and physicians’ PPI prescription persistence. A fixed combination of enteric-coated naproxen and immediate-release esomeprazole has just been approved by the US Food and Drug Administration. PPI combinations with aspirin, other tNSAIDs, and coxibs are desirable. Patients in all risk groups, even patients at low risk of GI adverse events, benefit from concomitant protective measures. Moreover, the literature suggests that NSAID/PPI combinations are cost effective, including for patients in low-GI-risk groups. Pricing of fixed NSAID/PPI combinations will play a pivotal role for their broad acceptance in the future.

Keywords: PPI, NSAID, fixed combination, gastrointestinal, adverse events, prevention