The possibility of modulating the treatment regimen regarding dose reduction (de-escalation) or dose augmentation (escalation) in psoriasis biological treatment has been of increasing interest. De-escalation strategies include reducing the single therapeutic dose, the mg/kg ratio or the number of injections, or dose-spacing (D-S), that is, extending the interval between administrations. Data regarding dose de-escalation, in particular D-S, on IL-23, are lacking to date. The present pilot study is a cohort study with a retrospective analysis of the general characteristics and effectiveness outcomes of psoriatic patients undergoing therapeutic biologic D-S of risankizumab and guselkumab. Ninety-four patients, 32 (34.04%) treated with guselkumab and 62 (65.96%) treated with risankizumab, underwent dose modulation by D-S of 50% of the approved range. The mean PASI decreased from 12.15 (5.43 SD) to 0.15 (0.46 SD) at D-S time. Attainment of PASI100 was rapid: 88.3% at the D-S date, remaining stable over the following year, reaching 100% of patients observed 12 months after D-S. Similar is the trend for PASI 90 and PASI <
=1 with 91.49% and 97.87% of achievement at D-S date, and all patients observed at 12 months post-D-S. The 12-month drug survival of the D-S regimen was 89.4%. Guselkumab showed a D-S drug survival of 93.3% versus 89.5% of risankizumab. No differences in mean PASIs at each time point were found between guselkumab and risankizumab. To conclude therapeutic modulation of IL-23 inhibitors in psoriatic patients who have achieved response stability seems a legitimate therapeutic strategy to maintain efficacy and safety.