TNF and rheumatoid arthritis: Pioneering studies have revealed the presence of a TNF-dependent proinflammatory cytokine cascade in several IMIDs, and the introduction of anti-TNF therapy 20 years ago has proven effective to reduce inflammation and clinical symptoms in RA, SpA, and other IMID, providing unprecedented clinical benefits and a valid alternative in case of failure or intolerable adverse effects of conventional disease-modifying antirheumatic drugs (DMARDs, for RA) or non-steroidal anti-inflammatory drugs (NSAIDs, for SpA).