Effect of secukinumab dose escalation on MRI-detected inflammation and structural damage in axial spondyloarthritis: a clinical, investigator-initiated, treat-to-target study (TRACE)

司库奇尤单抗剂量递增对中轴型脊柱关节炎MRI检测到的炎症和结构损伤的影响:一项临床研究者发起的以治疗为目标的研究(TRACE)

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Abstract

INTRODUCTION: Evidence of treat-to-target strategies including secukinumab dose escalation in patients with axial spondyloarthritis (axSpA) remains limited. We investigated the effect of a treat-to-target approach aiming for Axial Spondyloarthritis Disease Activity Score (ASDAS) remission, assessed by clinical and MRI outcomes over 24 weeks. METHODS: TRACE was a multicentre study including biologic-naïve patients with active axSpA. Sixteen weeks after secukinumab 150 mg initiation, patients in ASDAS remission (<1.3)(week 16 remitters) continued the same dose, while non-remitters (week 16 non-remitters) escalated to 300 mg/month. Sacroiliac joint (SIJ) and spine MRIs were performed at baseline, weeks 4, 16 and 24, and centrally scored using Spondyloarthritis Research Consortium of Canada (SPARCC) and Canada-Denmark scores for inflammation and structural lesions. The primary end point was total MRI-inflammation improvement ≥2 (weeks 16-24) comparing week 16 remitters and week 16 non-remitters. RESULTS: Of 90 patients, 68% were male, mean age was 35.4 years. At week 16, 30 (35%) patients achieved ASDAS remission. At week 24, 36 (49%) patients were in ASDAS remission, including 10 (22%) week 16 non-remitters, who responded after dose escalation (dose-escalation responders).Already at week 4, marked reductions in total MRI inflammation (SPARCC spine+SIJ) (-14.7), and structural lesion remodelling (reduced SIJ erosion; increased SIJ fat and backfill), were observed. These changes continued through week 16, with only minor improvements thereafter.The primary end point occurred in 14 (52%) of week 16 remitters versus 19 (41%) of week 16 non-remitters (p=0.53). Dose-escalation responders had a numerically larger mean total MRI inflammation reduction (-6.1) than dose-escalation non-responders (-2.2). CONCLUSION: No statistically significant effect of secukinumab dose escalation on reducing MRI-detected inflammation was observed, except in a selected subgroup of patients. However, 22% achieved ASDAS remission after dose escalation. Notably, substantial MRI-detected inflammation reduction and structural remodelling occurred within the first 4 weeks. TRIAL REGISTRATION NUMBER: NCT03639740.

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