MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16

M Østergaard, L T H Jacobsson, C Schaufelberger, M Sejer Hansen, J W J Bijlsma, A Dudek, M Rell-Bakalarska, F Staelens, R Haake, B Sundman-Engberg, H Bliddal, M Østergaard, L T H Jacobsson, C Schaufelberger, M Sejer Hansen, J W J Bijlsma, A Dudek, M Rell-Bakalarska, F Staelens, R Haake, B Sundman-Engberg, H Bliddal

Abstract

Objectives: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA).

Methods: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures.

Results: Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group.

Conclusions: CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.

Trial registration number: ClinicalTrials.gov, NCT01235598.

Keywords: Anti-TNF; Inflammation; Magnetic Resonance Imaging; Rheumatoid Arthritis; Synovitis.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
(A) Study design (double-blind period) and (B) patient disposition. ACR, American College of Rheumatology; AE, adverse event; CZP, certolizumab pegol; DMARDs, disease-modifying antirheumatic drug; MARVELOUS, MAgnetic Resonance image VErified earLy respOnse on rheUmatoid factor positive arthritiS; RA, rheumatoid arthritis.
Figure 2
Figure 2
Changes in Outcome Measures in Rheumatology Clinical Trials (OMERACT) rheumatoid arthritis MRI scoring system (RAMRIS) parameters in the placebo→certolizumab pegol (CZP) group and CZP group. (A) Median change from baseline in synovitis score over 16 weeks. (B) Median change from baseline in bone oedema score over 16 weeks. (C) Table summarising median change in synovitis and bone oedema score for each MRI reading. CI, confidence interval; NS, non-significant.
Figure 3
Figure 3
Clinical efficacy to week 16, as measured by (A) European League against Rheumatism (EULAR) response, (B) American College of Rheumatology (ACR) 20 response, (C) median Disease Activity Score 28 (DAS28) C reactive protein (CRP) score and (D) patient-reported outcomes measured by median Health Assessment Questionnaire-Disability Index (HAQ-DI) score (observed data). CZP, certolizumab pegol.

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