Discussion
PsA, PsA., RP, tumor necrosis, inflamed joints
TUMOR NECROSIS
This post hoc analysis of the phase 3 DISCOVER-2 trial data revealed that, in patients with active PsA treated with guselkumab, achievement of earlier (Week 8) meaningful improvement in DAPSA score was significantly associated with less RP through 2 years of treatment. Achievement of DAPSA score exceeding the Week 8 median and MCID improvement thresholds, as well as of attainment of DAPSA LDA at Week 8, was associated with a pattern of less RP through Week 100. Moreover, achievement of DAPSA LDA at Week 8 was associated with less RP at Week 52, with further suppression of joint damage progression at Week 100. These findings were observed after adjusting for previously documented predictors of RP including older age, male sex, increased CRP levels, and higher baseline levels of structural damage [The DAPSA score is a composite measure of the musculoskeletal domain of PsA and is based in part on an evaluation of actively inflamed joints and CRP level, both shown to be predictors of radiographic damage [A number of treatment options are available in PsA across therapeutic classes including anti-IL-12/23 agents, IL-17A inhibitors acting downstream of IL-23, tumor necrosis factor inhibitors (TNFi), small molecules, and cytotoxic T-lymphocyte-associated antigen 4 inhibitors, all with demonstrated ability to significantly improve skin and joint symptoms [Consistent with previous studies, the present analysis showed that elevated baseline CRP concentration, as well as higher baseline radiographic score, were predictive of future joint damage [Several limitations of the current post hoc analyses should be noted. Results of analyses conducted on a clinical trial population enriched for patients with a higher risk of RP and no history of biologic therapy may have limited external validity to the broader population of patients with PsA. A follow-up duration of 100 weeks may not be sufficient to evaluate RP in PsA; hence, the ongoing APEX phase 3b study (NCT04882098), designed to evaluate guselkumab efficacy in the inhibition of RP in patients with PsA through 3 years, may offer greater insight into long-term effects of guselkumab. These analyses were conducted post hoc, and the DISCOVER-2 study was not adequately powered to answer the question under study, which may have resulted in lack of statistical significance for certain associations. Strengths of the present analysis include the low guselkumab discontinuation rates in the DISCOVER-2 trial, and the use of DAPSA, a validated PsA assessment instrument. Although safety analyses were out of scope for these post hoc analyses, previous reports have demonstrated the favorable safety profile of guselkumab during the placebo-controlled study period, with consistent findings through up to 2 years of follow-up among patients with PsA [