Predictive value of gastrointestinal symptoms and patient risk factors for NSAID-associated gastrointestinal ulcers defined by endoscopy? Insights from a pooled analysis of two naproxen clinical trials.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and rheumatic conditions. To facilitate patient management, we determined the predictive value of gastrointestinal (GI) symptoms and risk factors for the development of NSAID-associated GI injuries. METHODS: Post-hoc analysis of pooled data from naproxen treatment arms of two identical, randomized, double-blind, controlled phase 3 trials in arthritis patients at risk of GI adverse events. Endoscopic incidence of GI ulcers at baseline, and 1, 3, and 6 months was employed as a surrogate parameter for GI injury. For GI symptom analysis, Severity of Dyspepsia Assessment questionnaire was used. For GI risk factor analysis, the high risk factors: previous GI injury, concomitant selective serotonin reuptake inhibitors or corticosteroids, ulcer history, concomitant low-dose aspirin, and age >65 years were employed. RESULTS: Data of 426 naproxen patients were analyzed. Distribution of GI symptoms between patients with and without ulcer was similar; about one third of patients developing an ulcer reported no GI pain symptoms. GI symptoms experienced under naproxen treatment were thus not indicative of GI injury. The proportion of patients developing an ulcer increased with the number of risk factors present, however, about a quarter of patients without any of the analyzed risk factors still developed an ulcer. CONCLUSION: GI symptoms and the number of risk factors are not reliable predictors of NSAID-induced GI injury to decide which patients need gastroprotection and will lead to a large group of patients with GI injuries. A preventive rather than reactive approach should be taken.

Comparative Benefit-Risk Assessment for Lidocaine 700 mg Medicated Plaster and Pregabalin in Peripheral Neuropathic Pain Following a Structured Framework Approach.

INTRODUCTION: Peripheral neuropathic pain (PNP) is difficult to treat. Several oral drugs are recommended as first-line treatments. Nevertheless, many patients cannot obtain sufficient pain relief or do not tolerate systemically active treatments. Topical treatments, with a lower risk of systemic side effects such as lidocaine 700 mg medicated plaster, are also recommended in treatment guidelines. This analysis compares the benefit-risk balance of topical 700 mg lidocaine medicated plaster with the benefit-risk balance of oral pregabalin administration for the treatment of PNP following current recommendations on benefit-risk assessment (BRA) methodology. METHODS: The Benefit-Risk Action Team (BRAT) framework was used as structured approach. Selection of key benefits and risks was supported by a patient survey. Published randomized controlled clinical trials were the main source to identify data related to key benefits and risks. The outcome of randomized clinical trials was compared with real-world evidence (RWE) data for consistency. RESULTS: Identified key benefits were pain reduction and improvement in quality of life. Key risks identified were application site reactions, dizziness, confusion, weight gain, peripheral edema, and blurred vision. Overall, there was similarity in key benefits between the comparators; however, a clear advantage regarding key risks in favor of lidocaine 700 mg medicated plaster was observed. This observation was consistent across data from a direct comparison trial, randomized placebo-controlled trials, as well as data from RWE studies. The low number of randomized controlled trials for lidocaine 700 mg medicated plaster was the main limitation. CONCLUSION: Guided by the opinion of patients regarding key benefits and risks deemed important for treatments of peripheral neuropathic pain, our analysis showed that lidocaine 700 mg medicated plaster has a more favorable benefit-risk balance compared to pregabalin (300 and 600 mg daily).