AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis.

Paul Bird,Hedley Griffiths,Fredrick Joshua,Stephen Hall,Rina Barrett,Charles Peterfy,Peter Countryman,Peter Youssef

doi:10.1155/2018/8721753

Abstract

Aim Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). Methods In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). Results 52 subjects were enrolled (80% female, mean (SD) age 57 (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. Conclusion Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. Trial registration This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703).

Highlights

Imaging assessment of structural damage in subjects with rheumatoid arthritis (RA) has been traditionally centred around conventional radiography (X-ray)
This Australian substudy is part of an umbrella project consisting of several independent studies with similar designs conducted in various countries [5]; safety and efficacy data will be pooled for a global analysis, with the primary objective of assessing safety of subcutaneous tocilizumab (SC-TCZ)
Fifty-one subjects completed the study follow-up period; one subject was withdrawn by decision of the investigator due to suspected hypersensitivity reaction, which was subsequently downgraded to an injection site reaction

Summary

Introduction

Imaging assessment of structural damage in subjects with rheumatoid arthritis (RA) has been traditionally centred around conventional radiography (X-ray). X-ray cannot provide information regarding inflammatory changes in synovium, bone, or tendon sheaths and is relatively insensitive for bone erosion. It cannot define articular cartilage loss directly, and cartilage loss can only be surmised by narrowing of the lucent joint space. Physicians and investigators are turning increasingly to magnetic resonance imaging (MRI) for earlier detection of bone erosion, osteitis, and synovitis and to evaluate the integrity of articular cartilage, tendons, ligaments, and other structures important to joint function. In an MRI substudy of ACT-RAY, IV-TCZ was shown to decrease synovitis and osteitis within 2 weeks and inhibit bone erosion within 12 weeks [3]

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Results

Discussion

Conclusion