The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial

Abstract

ObjectiveTo evaluate radiographic progression in patients with ankylosing spondylitis (AS) receiving two different doses of the tumour necrosis factor antagonist golimumab.Methods356 patients with AS were randomly assigned to placebo, or golimumab 50 mg or 100 mg every 4 weeks (wks). At wk16, patients with inadequate response early escaped with blinded dose adjustments (placebo→golimumab 50 mg, 50 mg→100 mg). At wk24, patients still receiving placebo crossed over to golimumab 50 mg. Lateral view radiographs of the cervical/lumbar spine were obtained at wk0, wk104 and wk208, and scored (two blinded readers, modified Stoke AS Spine Score (mSASSS)). Observed data were used for wk104 analyses; missing wk208 scores were linearly extrapolated.ResultsWk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover, 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg. By wk208, following golimumab therapy for 3.5–4 years, mean changes in mSASSS were 2.1±5.2 for placebo crossover, 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg. Less than a third of patients (placebo crossover, 19/66 (28.8%); 50 mg, 29/111 (26.1%); 100 mg, 35/122 (28.7%)) had a definitive change from baseline mSASSS (>2). Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes (0.2 vs 2.8 in patients with ≥1 syndesmophyte; p<0.0001) and with baseline C-reactive protein (CRP) levels ≤1.5 mg/dl (0.9 vs 2.9 with CRP >1.5 mg/dl; p=0.0004).ConclusionsNo difference in mSASSS change was observed between golimumab 50 mg and 100 mg. The radiographic progression rate remained stable at years 2 and 4, suggesting no acceleration of new bone formation over time. Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression.

Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab

“…The Journal of on May 7, 2018 -Published by www.jrheum.org Downloaded from observed in the GO-RAISE study 8 . Per the EASIC imaging data, the combination of an inflammatory lesion with a fat MRI signal most commonly yielded new bone formation 22 .…”

“…Image sequences were scored using the Ankylosing Spondylitis spine MRI-activity (ASspiMRI-a) score (range 0-138) 2,21 . Radiographs and MRI scans were read by 2 qualified, experienced, and independent readers who were blinded to treatment information, patient identity, and chronology of the images, as described previously 2,8 .…”

“…The ability of anti-TNF intervention to reduce spinal radiographic progression is less clear 4,5,6,7,8 . A biomarker measured prior to/early in anti-TNF therapy that can reliably predict longterm response or reduced radiographic progression would be valuable.…”

Unanswered questions in the management of axial spondyloarthritis: an opinion piece

“…Most non-responders to a conventional infliximab regimen did respond to dose escalation in one study [31], similar to the clinical experience of practicing rheumatologists. Recent studies of TNFi have evaluated the differences in efficacy of different doses (golimumab and etanercept) or dosing intervals (certolizumab) in patients with axSpA, but the findings were negative [5,32,33]. Dose deescalation of TNFi in patients who are in remission would have important economic implications.…”

TUMOR NECROSIS FACTOR-α INHIBITORS IN THE TREATMENT OF AXIAL SPONDYLOARTHRITIS, INCLUDING ANKYLOSING SPONDYLITIS

“…Хотя прямых сравнительных исследова-ний по эффективности разных иФНОα при АС не проводилось, сопоставление результа-тов контролируемых и когортных исследова-ний показало, что все препараты этой группы (ИНФ, АДА, ЭТЦ, ГЛМ, ЦЗП) обладают сходной эффективностью в отношении ос-новных проявлений заболевания (спондилит, артрит и энтезит) на разных стадиях заболева-ния [19][20][21][22]. Имеются данные об улучшении функциональных возможностей у больных АС даже при полном анкилозе позвоночника.…”