Multiple randomised controlled trials (RCTs) have compared the efficacy of targeted therapies for the treatment of moderate-to-severe plaque psoriasis with placebo. However, the relative effectiveness of these treatments is not studied sufficiently. The aim of this study was to compare the effectiveness and safety of targeted drugs (netakimab, ixekizumab, guselkumab, secukinumab, ustekinumab, certolizumab, infliximab, adalimumab, etanercept, tofacitinib and apremilast) in adult patients with moderate-to-severe plaque psoriasis using such outcomes as PASI 75/90/100, PGA/IGA, DLQI, AEs, SAEs and withdrawals due to AEs. Material and methods. We performed a systematic literature review in PubMed database and in the CENTRAL section of Cochrane library (Embase filter) to identify relevant RCTs. The primary outcome was Psoriasis Area and Severity Index (PASI) 75 response at week 12 of treatment. Other analyzed outcomes: PASI 90/100, Physician’s Global Assessment (PGA) /IGA, Dermatology Life Quality Index (DLQI), number of patients suffering from at least one adverse event (AE) / severe AE and number of patient withdrawals from the study due to AE during initial 12 weeks of treatment. For each outcome we conducted network meta-analyses (NMAs) and univariate meta-regression analyses to adjust for baseline risk differences and cross-trial differences. Results. We selected 35 RCTs. We conducted several types of NMAs for each outcome to avoid bias in research. In most cases random effects NMAs adjusted to differences in placebo response rate provided the best model fit statistics and were selected for interpretation. Pairwise indirect comparisons from most NMAs suggested IL-17 inhibitors (netakimab and ixekizumab) along with IL-23 inhibitor guselkumab have superior effectiveness and favorable safety profile compared to other targeted therapies used to treat adults with moderate-to-severe plaque psoriasis during initial 12 weeks of therapy based on PASI 75/90/100, PGA/IGA, and DLQI.