Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients with rheumatoid arthritis and an inadequate response to methotrexate: the ASSET randomised controlled trial

Abstract

ObjectivesThis randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis.MethodsPatients received intravenous abatacept (∼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS.Results26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was −0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was −0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were −1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12.ConclusionsDespite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept.Clinical trial registrationClinicaltrials.gov NCT00420199.

Evaluation of changes in magnetic resonance images following 24 and 52 weeks of treatment of rheumatoid arthritis with infliximab, tocilizumab, or abatacept

“…The ACT-RAY MRI substudy reported early improvement of synovitis of RA patients after initiation of treatment with TCZ (17). The ASSET trial evaluated the clinical efficacy and safety of ABT as well the effect of treatment on MR imagings (18). To our knowledge, the present study is the first to compare MRI findings in RA patients treated with these three biologics.…”

“…In the ACT-RAY MRI substudy, Conaghan et al (17) reported significant improvement in MRI-detected synovitis after 2 weeks of treatment. The ASSET clinical trial evaluated the effects of ABT on various MRI findings, such as synovitis, BME and bone erosion (18). The present retrospective study compared the MRI findings in RA patients treated with the biologic DMARDs; IFX, TCZ and ABT during 52 weeks.…”

Results of the Iv Phase of the Open Clinical Trial on Efficacy and Safety of Abatacept Usage in Children and Adolescents With Polyarticular Juvenile Idiopathic Arthritis Without Systemic Manifestations in Russia

“…Эффективность и безопасность абатацепта исследо-вали в рандомизированных двойных слепых плацебо-контролируемых исследованиях у пациентов в возрасте старше 18 лет с активным ревматоидным артритом, рефрактерных к одному из иммунодепрессантов и/или ингибитору фактора некроза опухоли (ФНО) ␣ [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Особый интерес представляет рандомизированное двойное слепое плацебоконтролируемое исследование эффективности и безопасности абатацепта, в которое были включены 190 детей в возрасте от 6 до 17 лет с различными вариантами ЮИА (олиго-, полиартрит РФ-и РФ+, системный вариант без системных проявлений) [34].…”

Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

“…Erosions, bone edema, and synovitis depicted by MRI have been shown to cover all aspects of truth 12,13,14,15,16,17 , and the RA MRI score (RAMRIS) for erosions, bone edema, and synovitis has also demonstrated responsiveness and discrimination 18,19,20,21,22 . Although feasibility issues such as accessibility, time, cost, and patient compliance may cause limitations in clinical practice, MRI is acceptable for clinical trials.…”