The placebo effect in psoriatic arthritis

The placebo effect represents a clinically relevant and underexplored phenomenon in modern medicine with significant implications for treatments, particularly in rheumatological conditions, as placebo groups in clinical trial commonly achieve some degree of subjective and objective response, with an unclear correlation from the routine clinical observations. Emerging evidence highlights that the placebo effect extends beyond symptom perception, modulating markers of inflammation through neuroimmune pathways; however, these mechanisms remain poorly understood. In psoriatic arthritis (PsA), the placebo effect is of particular relevance, given the heterogeneous disease manifestations, the frequent neuropsychiatric disturbances, and the relevance of non-inflammatory or nociplastic pain. We herein provide a narrative review of the placebo responses observed in PsA clinical studies, the methodological challenges in isolating real drug effects, particularly in terms of allowed or background medications. We also emphasize the role of the placebo response in PsA and the broad aspects of the disease that influence the perception of pain in those patients, such as the physician and patient expectations, metabolic comorbidities and socio-economic background. A deeper understanding and systematic integration of placebo metrics and contextual determinants into future studies will be essential to accurately interpret drug efficacy and optimize trial methodology in this most heterogeneous disease.