Optimizing Analgesic Therapy in Patients with Rheumatic Diseases at Increased Gastrointestinal Risk: A Narrative Review

Background: Chronic rheumatic pain often requires sustained analgesia, while non-steroidal anti-inflammatory drugs (NSAIDs) are simultaneously among the most effective agents and a major cause of gastrointestinal (GI) injury. Direct evidence in patients with rheumatic disease and established GI or hepatic comorbidity is exceptionally sparse. Objective: To synthesize the mechanistic, trial, meta-analytic and guideline evidence needed to balance analgesic benefit against GI and cardiovascular (CV) harm in adults with rheumatic disease at increased GI risk. Methods: This structured narrative review used purposive searches of PubMed/MEDLINE and the Cochrane Library, supplemented by reference-list screening. Thirty-nine sources were retained for relevance and methodological quality. No protocol was registered, screening was not duplicated, formal risk-of-bias tools were not applied and no de novo meta-analysis was performed; effect estimates are therefore reported on their native endpoints and interpreted as a reasoned synthesis. Results: PPIs are the reference gastroprotective co-therapy (risk ratio 0.29 for incident endoscopic ulcers versus placebo). Standard-dose H2-receptor antagonists provide weaker protection, misoprostol is effective but limited by tolerability, and potassium-competitive acid blockers remain an emerging, jurisdiction-dependent option rather than a universal first-line substitute. In high-GI-risk patients, a COX-2-selective inhibitor plus a PPI is the best-supported NSAID-based strategy (ulcer-complication risk ratio 0.07 in network meta-analysis), but concomitant aspirin attenuates GI benefit and vascular risk differs materially among NSAIDs. When both GI and CV risks are high, avoiding systemic NSAIDs where feasible and emphasizing non-NSAID and multimodal non-pharmacological care is the most defensible orientation. Conclusions: Analgesic selection should be based on joint GI–CV risk, the lowest effective exposure and repeated reassessment. The proposed matrix is an evidence-synthesis heuristic, not a validated clinical algorithm, and individual decisions require clinician assessment of comorbidity, concomitant therapy and patient preferences.