Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis

Abstract

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3, placebo-controlled, randomised trial, DISCOVER-2.MethodsBiologic-naïve adults with active PsA (≥5 swollen joints /≥5 tender joints ; C reactive protein ≥0.6 mg/dL) were randomised to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then every 8 weeks (Q8W); or placebo→guselkumab 100 mg Q4W (week 24). Radiographs (hands/feet) at week 0, week 24, week 52 and week 100 were scored via PsA-modified van der Heijde-Sharp (vdH-S) methodology. In these post hoc analyses, mean changes in vdH-S scores were summarised according to achievement of American College of Rheumatology 20/50/70 response; low disease activity (LDA) defined by Disease Activity in Psoriatic Arthritis (DAPSA) ≤14 or Psoriatic ArthritiS Disease Activity Score (PASDAS) ≤3.2, or minimal/very low disease activity (MDA/VLDA); and normalised physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤0.5). Response rates for achieving MDA/VLDA and each component were determined among patients with and without radiographic progression (change in total vdH-S score >0.5). No formal hypothesis testing was performed.Results664 of 739 treated patients in DISCOVER-2 continued study treatment at week 52 and were included in these analyses. Mean changes in vdH-S scores from weeks 0 to 100 among all patients in the Q4W and Q8W groups were 1.7 and 1.5, respectively. Among all guselkumab-randomised patients, those who achieved ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, VLDA and HAQ-DI ≤0.5 (normalised physical function) had smaller mean changes in vdH-S scores than did non-responders at week 52 (0.2–1.2 vs 1.7–4.1) and week 100 (0.3–1.2 vs 2.0–4.6). Relative to patients with radiographic progression, those without progression were more likely to achieve the MDA criteria related to swollen and tender joint counts, patient-reported pain and global assessment, and normalised physical function through week 100.ConclusionIn these post hoc analyses, the achievement of low levels of disease activity, including MDA, was associated with diminished rates of radiographic progression observed in patients receiving up to 2 years of guselkumab. Radiographic non-progressors were more likely to achieve patient-reported MDA criteria of minimal pain and normalised physical function compared with radiographic non-responders.Trial registration numberNCT03158285.

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry

“…Achievement of minimal levels of disease activity is an important outcome [34] that has been shown to be associated with low rates of radiographic progression [35] and long-term improvements in health-related quality of life and functional ability [35,36]. Specific to guselkumab, results of a recent analysis from the 2-year DISCOVER-2 study, which enrolled bio-naı ¨ve patients with active PsA and an elevated risk of future structural damage, showed that patients with active PsA receiving guselkumab who achieved low levels of disease activity (including MDA) generally had lower rates of radiographic progression, on average, than patients who did not achieve these treatment targets [37]. Patients in the realworld Spanish and Italian cohorts who received guselkumab for PsA also realized significant improvements in articular and skin manifestations at 6 months [30,31].…”

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment

“… Table adapted from [ 10 , 16 ]. Data are mean (SD) unless otherwise stated a DAPSA score: remission ≤ 4, low disease > 4 to ≤ 4, moderate disease > 14 to ≤ 28, high disease activity > 28 b Reading session 1 included randomized patients who received ≥ 1 administration of study drug (partial or complete) and had radiographic images obtained at Weeks 0 and 24 (or at discontinuation prior to Week 24) c Reading session 3 included patients continuing study treatment at Week 52 with images at Weeks 0, 24, 52 and 100 (or at discontinuation after Week 52) BSA = body surface area; CRP = C-reactive protein; DAPSA = Disease Activity Index for PsA; DSS = Dactylitis Severity Score; HAQ-DI = Health Assessment Questionnaire-Disability Index; IGA = Investigator’s Global Assessment; IQR = interquartile range; JSN = joint space narrowing; LEI = Leeds Enthesitis Index; PASI = Psoriasis Area and Severity Index; PsA = psoriatic arthritis; Q4W = every 4 weeks; Q8W = every 8 weeks; SJC = swollen joint count; TJC = tender joint count; vdH-S = van der Heijde-Sharp …”

“…In the majority of patients, response rates were maintained or increased at 1 year [ 15 ]. In the DISCOVER-2 trial of biologic-naïve patients with active PsA, guselkumab Q4W showed significantly less progression of structural damage at Week 24 compared with placebo [ 10 ], and low rates of radiographic progression (RP) were observed through 2 years of guselkumab treatment regardless of the dosing regimen [ 13 , 14 , 16 ]. Furthermore, patients receiving guselkumab Q4W or Q8W who achieved clinical responses across several global measures of PsA disease activity or normalized physical function at 1 or 2 years of treatment, showed less RP through Week 100 compared with nonresponders [ 16 ].…”

“…In the DISCOVER-2 trial of biologic-naïve patients with active PsA, guselkumab Q4W showed significantly less progression of structural damage at Week 24 compared with placebo [ 10 ], and low rates of radiographic progression (RP) were observed through 2 years of guselkumab treatment regardless of the dosing regimen [ 13 , 14 , 16 ]. Furthermore, patients receiving guselkumab Q4W or Q8W who achieved clinical responses across several global measures of PsA disease activity or normalized physical function at 1 or 2 years of treatment, showed less RP through Week 100 compared with nonresponders [ 16 ]. Supporting these findings, levels of inflammatory biomarkers, including C-reactive protein (CRP), and biomarkers of collagen degradation across diseases with musculoskeletal involvement, such as tissue metabolite of type I collagen (C1M), both known predictors of structural damage [ 17 – 21 ], were significantly suppressed at 24 weeks of guselkumab treatment with sustained reductions through 1 year [ 22 , 23 ].…”

Search for predictors of achieving minimal disease activity during tofacitinib therapy in patients with psoriatic arthritis

“…Так, в испанском многоцентровом исследовании было выявлено, что достижение МАБ сопровождается более выраженным повышением КЖСЗ пациентов, оцениваемого по опроснику PsAID-12 (Psoriatic Arthritis Impact of Disease) [6]. В ряде работ было показано, что достижение целей терапии: МАБ, низкой активности болезни или ремиссии по индексу DAPSA (Disease Activity In Psoriatic Arthritis), значимого функционального улучшения по HAQ-DI (Health Assessment Questionnaire Disability Index) на фоне применения таргетных препаратов, в частности ингибитора интерлейкина (иИЛ) 23 гуселькумаба, иИЛ17А секукинумаба, является предиктором снижения риска рентгенологического прогрессирования [7,8].…”