TNF and Arthritis: Mechanistically, irAEs were associated with CTLA-4 and PD-1/PD-L1 inhibition, resulting in aberrant T-cell activity and cytokine release (e.g., IL-1β, TNF-α), which induces cross-reactive autoimmunity against synovial antigens, in contrast to temporary non-rheumatic irAEs [121].In addition, examination of 372 cases of ICI-induced arthritis indicated that around 50% manifested polyarthritis, whereas a minority displayed symptoms akin to polymyalgia rheumatica; the majority of patients tested seronegative for RF and anti-CCP [122].