Guselkumab showed improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) in patients with active psoriatic arthritis (PsA) and imaging-confirmed sacroiliitis, according to study results published in Lancet Rheumatology.
Guselkumab is a human monoclonal antibody that specifically targets the p19 subunit of interleukin (IL)-23, an upstream regulatory cytokine implicated in the pathogenesis of PsA.
Two phase 3, randomized, double-blind, placebo-controlled studies, DISCOVER-1 and DISCOVER-2, evaluated the efficacy and safety of guselkumab in patients with PsA. Patients in both studies were randomly assigned to receive subcutaneous injections of 100 mg guselkumab every 4 weeks, 100 mg guselkumab at weeks 0 and 4 and every 8 weeks thereafter, or placebo every 4 weeks. At week 24, all patients who received placebo were initiated on guselkumab 100 mg every 4 weeks. Patients who received guselkumab had reduced signs and symptoms of active PsA than those who received placebo.
In the current post-hoc analysis, researchers included patients with PsA and axial involvement with radiologic evidence of sacroiliitis to examine the effect of guselkumab. Symptoms associated with axial involvement were assessed using the BASDAI and ASDAS scores) using C-reactive protein (CRP).
Patients with PsA may also present with human leukocyte antigen (HLA)-B27, which is thought to be associated with axial involvement and more severe disease. An additional exploratory analysis was conducted to identify whether guselkumab may be effective for patients who tested positive and negative for HLA-B27.
Of the 312 patients (61% men; mean age, 45.1±11.2 years) with PsA and sacroiliitis, 118 were in the placebo group, 103 in the guselkumab every-4-weeks group, and 91 in the guselkumab every-8-weeks group. A total of 190 (61%) patients had data needed for determining HLA-B27 status, of whom 57 (30%) tested positive for HLA-B27.
Improvements in BASDAI and ASDAS scores were greater in the guselkumab groups compared with the placebo group at weeks 8 and 16 (P <.01 for all). Based on least mean squares changes, at week 24, patients who received guselkumab vs placebo had greater improvements in BASDAI (difference of -1.3 [95% CI, -1.9 to -0.7] for both guselkumab groups). Outcome measures at week 52 were similar across all groups, including among patients who received placebo and then crossed over to receive guselkumab every 4 weeks at week 24. Researchers suggested that guselkumab was effective in reducing axial symptoms in this cohort.
In the HLA-B27 analysis, scores at week 24 were greater in the guselkumab groups than in the placebo group for patients who were HLA-B27-positive and those who were HLA-B27-negative (P <.01 for all). At week 52, no difference was seen in BASDAI and ASDAS in both sets of patients.
Study limitations included the small sample size and the possibility of other HLA-B alleles being associated with axial PsA. The post hoc nature of the analysis and the DISCOVER studies being underpowered for a specific subgroup of patients were also limitations. The study was also restricted by lack of post-baseline imaging to assess changes during treatment.
“This post hoc analysis suggests that therapies inhibiting the IL-23 p19 subunit might be effective in addressing axial symptoms in patients with [PsA],” the researchers noted.
“A prospective, [randomized], controlled trial of guselkumab in patients with [PsA] with axial involvement will test this hypothesis further ([ClinicalTrials.gov Identifier:] NCT04929210), they concluded.
Disclosure: This research was supported by Janssen Research and Development LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a list of full disclosures.
Mease PJ, Helliwell PS, Gladman DD, et al. Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studies. Lancet Rheumatol. Published online June 29, 2021. doi:10.1016/S2665-9913(21)00105-3