Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis

Abstract

Objective The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA). Methods A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs). Results Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks. Conclusions In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS)

“…23 In addition, the rates of AEs and SAEs were generally similar across treatment modalities; however, comparisons were limited by the significant uncertainty in the comparisons. 23 It is generally recommended to switch to an alternate mechanism of action following biologic treatment failure, 1 2 with only one switch between TNFi now recommended by the European Alliance of Associations for Rheumatology. 2 The demonstrated efficacy of therapies targeting the IL-12/23p40-subunit, IL-17A, and Janus kinases in TNFi-experienced patients with PsA [24][25][26][27] further supports the use of novel therapies to target alternative disease pathways.…”

Letter to the editor concerning the article: “Comparative safety and benefit-risk profile of biologics and oral treatments for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data”

“…Sbidian et al's 2 update of the Cochrane NMA for plaque psoriasis using similar data concluded that there were no short-term serious adverse effect safety differences among the same agents, and appropriately cautioned against attempting comparisons of safety due to reporting inconsistencies for such data. Mease et al's 3 NMA for psoriatic arthritis applied more rigorous standards for the display and interpretation of safety analysis. All data plots displayed statistical uncertainty around point estimates, and the authors appropriately did not make any firm conclusions regarding safety.…”

Guselkumab in psoriatic arthritis: a profile of its use

“…Like that of many other therapies approved for use in psoriatic arthritis, the efficacy of guselkumab in this indication was established in placebocontrolled trials and head-to-head comparisons with active treatments are currently lacking. Systemic reviews and network meta-analyses suggest that guselkumab is generally comparable to most other targeted treatments for psoriatic arthritis with respect to improvements in arthritis, soft tissue damage and physical function, as well as with respect to safety outcomes [36,37]. Guselkumab may provide greater improvements in psoriasis than some targeted psoriatic arthritis treatments [36,37], although the results of such indirect comparisons must be interpreted with caution.…”

“…Systemic reviews and network meta-analyses suggest that guselkumab is generally comparable to most other targeted treatments for psoriatic arthritis with respect to improvements in arthritis, soft tissue damage and physical function, as well as with respect to safety outcomes [36,37]. Guselkumab may provide greater improvements in psoriasis than some targeted psoriatic arthritis treatments [36,37], although the results of such indirect comparisons must be interpreted with caution. The 2019 EULAR recommendations for the management of psoriatic arthritis precede the approval of guselkumab, but suggest that a biologic DMARD should be commenced in patients with peripheral arthritis and an inadequate response to ≥ 1 conventional synthetic DMARD (and be considered in certain settings in patients with unequivocal enthesitis or predominantly axial disease) [9].…”