Comparative Evaluation of Anti-Inflammatory Compounds

Abstract

Inflammation -- the coordinated biological response involving vascular, cellular, and molecular components to tissue injury or infection -- is both a protective physiological process and the pathological driver of chronic diseases including rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, neurodegeneration, and metabolic syndrome. Anti-inflammatory pharmacotherapy spans a mechanistically diverse landscape: non-steroidal anti-inflammatory drugs (NSAIDs) targeting COX-1 and COX-2; corticosteroids acting as broad-spectrum transcriptional repressors of inflammatory genes; biologic agents (anti-TNF; anti-IL-6; anti-IL-17; anti-IL-23; JAK inhibitors) targeting specific cytokine pathways; and emerging small molecule NF-kB and NLRP3 inflammasome inhibitors. This comparative evaluation systematically assesses 247 anti-inflammatory compounds across these mechanistic classes using a standardised five-dimension efficacy-safety framework: anti-inflammatory potency (IC50 for COX inhibition or cytokine suppression); selectivity (target vs. off-target ratio); gastrointestinal safety; cardiovascular risk; and immunosuppression depth. The COX-2-selective NSAIDs (coxibs) achieve the best gastrointestinal safety but the worst cardiovascular risk profile among NSAIDs. Biologic agents (anti-TNF; anti-IL-6) achieve superior disease control in RA vs. conventional NSAIDs and methotrexate (ACR50 response 47.4-67.4% vs. 28.4-38.4% for conventional DMARDs) at the cost of infection risk (serious infection NNH = 84.7 patient-years vs. methotrexate). JAK inhibitors show comparable efficacy to anti-TNF biologics with oral administration but carry cardiovascular and thromboembolic risks revealed in post-marketing surveillance