Il-23

AFFINITY was a 91-patient phase 2a trial of dual blockade, subcutaneous guselkumab (anti-IL-23) 100 mg plus golimumab (anti-TNF) 50 mg versus guselkumab alone, every 4 weeks, in psoriatic arthritis that had not responded to one or two TNF inhibitors. It missed its primary endpoint: minimal disease activity at week 24 was 29% with the combination and 22% with guselkumab alone. ACR50 (44% vs 22%) and physical function favoured the combination, and a post hoc split by CRP found the benefit concentrated in patients with CRP of 0.3 mg/dL or more (MDA 32% vs 5%, ACR50 55% vs 14%), with a reversed signal in the low-CRP group. Skin, enthesitis and dactylitis responses were similar, and no new safety signal appeared through week 36.

Up to 30% of people with psoriasis develop psoriatic arthritis, and nobody can yet say which ones. This review argues the plaque is not just an inflamed patch of skin but a source of immune cells that reach the joint: T cell clones and myeloid precursors shared between skin and synovium. But arrival alone does not cause arthritis. What decides it is the stromal niche, in particular synovial fibroblasts, which act as gatekeepers.