ABSTRACTPalmoplantar pustular psoriasis (PPPP), or palmoplantar pustulosis (PPP), is a type of psoriasis that affects the skin on the palms and soles. It is characterised by dermatosis and small sterile pustules and is considered a significant burden on patients' quality of life, as there is currently no gold standard treatment or cure. This network meta‐analysis (NMA) compares the efficacy and safety of biologic and non‐biologic medications for PPPP and PPP. Medline, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. The efficacy and safety of all medications were assessed through a frequentist NMA using a random‐effects model. Treatments were ranked using the net rank function, yielding P scores. Fourteen RCTs with 1056 participants were included. Guselkumab 100 mg was the most effective for improving PPPGA scores (p = 0.72, RR = 1.31, CI: 0.31–5.57). Guselkumab 100 mg was ranked the highest for achieving PPPASI‐75 (RR = 5.4, CI: 1.26–23.2, p = 0.023). Oral cyclosporine 1 mg/kg/day was ranked the highest for PPPASI‐50 (RR = 2.10, CI: 0.65–6.82). Etretinate 1 mg/kg/day had the highest rate of adverse events (RR = 1.78, CI: 0.92–3.44). Secukinumab 300 mg was associated with the highest rate of serious adverse events (RR = 1.58, CI: 0.21–12.02). Based on the P‐scores from our NMA, guselkumab 100 mg was the most effective for PPPGA improvement, guselkumab 100 mg for PPPASI‐75, oral cyclosporine 1 mg/kg/day for PPPASI‐50, etretinate 1 mg/kg/day had the most adverse events, and secukinumab 300 mg was associated with the highest rate of serious adverse events.Trial RegistrationPROSPERO registration number: CRD42023460842
