Abstract
Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA). 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. 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. 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].
Highlights
The same ANOVA model was modified to exclude patients with missing Week 24 data, to use linear extrapolation for Week 24 scores for all patients who early escaped at Week 16 and for missing data, and to use the last observation carried forward (LOCF) to impute Week 24 scores for all patients with missing Week 24 scores
Patients who received IV GOL 2 mg/kg exhibited significantly less radiographic progression than placebo-treated patients from baseline to Week 24 when evaluated with an ANOVA model on the van der Waerden normal scores using linear extrapolation to impute missing data and with the same ANOVA model but using only observed data (–0.39 vs 2.08; p < 0.001), linear extrapolation for Week 24 scores for all patients who early escaped at Week 16 and for missing data (–0.37 vs 1.79; p < 0.001), and LOCF methodology to impute Week 24 scores for all patients with missing Week 24 scores (–0.38 vs 1.88; p < 0.001)
Subgroup analyses based on baseline demographics, disease characteristics, and concomitant therapy were consistent in favoring IV GOL over placebo in inhibiting radiographic progression
Summary
Single radiographs of the hands (posteroanterior) and feet (anteroposterior) were obtained at weeks 0 and 24 (or at the end of study if the patient discontinued prior to Week 24) They were read by 2 independent readers (and a third independent reader as an adjudicator in cases of a > 10-unit difference in total change score between readers or a missing total change score from one of the 2 primary readers) who were blinded to patient identity, treatment group, and assessment timepoint. Planned sensitivity analyses of the change in the total PsA-modified SvdH from baseline at Week 24 were conducted to evaluate alternative methods of handling missing data, including an ANOVA model on the van der Waerden normal scores with missing data imputed through linear extrapolation. A sample size of about 220 patients per treatment arm was estimated a priori to provide 90.7% power in detecting a significant treatment group difference in the mean change in total PsA-modified SvdH from baseline at Week 24
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