Impact of IL-23 inhibition versus methotrexate on select major fracture risk and progression to joint arthroplasty in psoriatic patients.

Abstract

Psoriasis is a chronic inflammatory skin disease linked to skeletal complications such as osteoporosis and fractures. Whether IL-23 inhibition via risankizumab (RZB) confers different long-term bone and joint outcomes than the conventional systemic agent methotrexate (MTX) remains uncertain. We aimed to compare patient characteristics between psoriatic adults initiating MTX versus RZB and to evaluate fracture and joint arthroplasty outcomes at 90 days, 2 years, and 5 years. We performed a retrospective cohort study using the TriNetX network. Adults ≥18 years with psoriasis initiating RZB (n = 5451) or MTX (n = 54,402) were included; those with prior major fractures or hip, knee, or shoulder arthroplasty were excluded. Propensity score matching (1:1) balanced demographics and comorbidities, yielding 5448 patients per group. Risk ratios (RRs) with 95 % CIs and p-values were calculated. Before matching, RZB initiators were younger, more often male, and had higher prevalences of hypertension and obesity, differences that became negligible after matching. RZB did not differ from MTX in fracture incidence or joint arthroplasty at 90 days or 2 years. At 5 years, RZB was associated with lower risk of shoulder or upper arm fracture (RR 0.491, CI 0.335-0.718), lumbar or pelvis fracture (RR 0.539, CI 0.370-0.787), and hip arthroplasty (RR 0.631, CI 0.437-0.910), with no significant differences in femoral fracture or knee arthroplasty. Among patients who underwent joint replacement, periprosthetic joint infection risk was similar (RR 0.82, CI 0.44-1.52). In this matched cohort, RZB was associated with lower 5-year risk of fractures compared with MTX, without an observed increase in periprosthetic joint infection. IL-23 inhibition, as achieved with RZB, may offer a more favorable long-term skeletal profile and help orthopedic surgeons contextualize skeletal risk in psoriasis.