Radiographic Progression Inhibition with Intravenous Golimumab in Psoriatic Arthritis: Week 24 Results of a Phase III, Randomized, Double-blind, Placebo-controlled Trial

Abstract

Objective.Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA).Methods.This phase III, randomized, double-blind, placebo-controlled trial (GO-VIBRANT) randomized patients with active PsA to receive IV placebo (n = 239) or IV GOL 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Radiographic progression (controlled secondary endpoint) was evaluated as change from baseline at Week 24 in PsA-modified total Sharp/van der Heijde scores (SvdH). The proportions of patients with a change from baseline at Week 24 in the total PsA-modified SvdH exceeding the smallest detectable change (SDC) or > 0 or 0.5 also were determined.Results.Overall, 474 patients (237/arm) contributed radiographic data. Results obtained from the 2 blinded, independent radiographic readers demonstrated good agreement (total score intraclass correlation coefficients: baseline = 0.93, Week 24 = 0.92, Week 24 change score = 0.73). GOL demonstrated significant inhibition of radiographic progression relative to placebo from baseline to Week 24 (mean changes in PsA-modified total SvdH: −0.36 vs 1.95; treatment difference: −2.32; p < 0.001). At Week 24, smaller proportions of GOL- versus placebo-treated patients demonstrated an increase in the total PsA-modified SvdH score exceeding the SDC (8.0% vs 27.0%, respectively; difference: −19.0%; p < 0.001), > 0 (28.3% vs 57.0%, respectively; difference: −28.7%; p < 0.001), or > 0.5 (18.6% vs 41.8%, respectively; difference: −23.2%; p < 0.001). Results were consistent for erosion and joint space narrowing scores, in hands and feet, and in patients with/without baseline concomitant methotrexate use. Prevention of radiographic progression by GOL was independent of clinical response.Conclusion.IV GOL is significantly better than placebo in inhibiting radiographic progression of structural damage in active PsA. [Clinical trial registration number (www.ClinicalTrials.gov): NCT02181673]

Inhibition of radiographic progression across levels of composite index-defined disease activity in patients with active psoriatic arthritis treated with intravenous golimumab: results from a phase-3, double-blind, placebo-controlled trial

“…Radiographs of the hands (posteroanterior) and feet (anteroposterior) obtained at weeks 0, 24, and 52 (or at the time of early discontinuation) were centrally read by two independent and blinded readers [27] and scored using the total Sharp/van der Heijde score (SHS) with modifications for patients with PsA, i.e., inclusion of distal interphalangeal joints in the hands, as well as pencil-in-cup and gross osteolysis deformities [28,29]. The total PsAmodified SHS (range, 0-528) sums the erosion (0-320) and joint space narrowing (JSN; 0-208) scores for 40 hand and 12 foot joints.…”

“…In total, 480 patients contributed data to the efficacy analyses, including 239 in the placebo group and 241 in the golimumab group. Of these, 474 patients contributed data to structural damage analyses, including 237 in each of the placebo and golimumab groups [27]. Demographic and disease characteristics were generally wellbalanced between the treatment groups, including baseline radiographic findings and disease activity.…”

Measurement properties of radiographic outcome measures in Psoriatic Arthritis: A systematic review from the GRAPPA-OMERACT initiative

“…[38] A number of RCTs have assessed the yield of assessing for proliferative features such as osteitis and ankyloses, and have not noted a significant progression in these features over time nor a significant difference between treatment arms. [14,15,21,22,27,[39][40][41][42] These findings, and the impact on feasibility if such features were to be included, suggest that there may be little value in modifications of the mTSS or the mSvDHs to include proliferative change.…”

Applying precision medicine to unmet clinical needs in psoriatic disease

“…In all RCTs showing that biologics (including anti-TNF [39], anti-IL-12-IL-23 [40] and anti-IL-17 [41,42] agents) reduce structural progression in PsA, structural progression was measured by scoring plain radiographs. These scores quantify some, but not all, of the following domains to varying degrees: joint space narrowing, erosion, osteoproliferation, ankylosis, osteolysis, osteopaenia and periostitis [43].…”

“…IL-17A itself can interact with stromal cells and macrophages, further perpetuating IL-1, IL-6 and TNF expression, thus providing a positive feedback loop for osteoclastogenesis. In patients with PsA, IL-17 antagonism has a positive effect on bone loss [41,63]; a reduction in bone erosions is also seen following TNF inhibition [39,64,65,66].…”