Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study

Abstract

Objective: To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis (AS) using MRI and DXA to monitor its impact on bone. Methods: In this single centre study 42 subjects with active AS were treated with methotrexate and were randomly assigned, in a ratio of 2:1, to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks. The primary outcome was improvement in disease activity as shown by the BASDAI at week 30. MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density. Results: Both therapeutic agents were well tolerated with no dropouts due to adverse events. A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 (p = 0.017) than in the placebo arm, but this was not maintained by week 30 (p = 0.195), 8 weeks after the last infusion, at which stage disease flares were reported by some subjects. MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group (p = 0.016). Conclusions: Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI. However, disease flares were reported 8 weeks after the last infusion, indicating that addition of methotrexate failed to extend the infliximab dosing interval.

Clinical and imaging efficacy of infliximab in HLA–B27–Positive patients with magnetic resonance imaging–determined early sacroiliitis

“…In this cohort, infliximab therapy resulted in significant suppression of MRI-determined inflammation relative to placebo, with a significant reduction in the total MRI score, increased resolution of inflammatory lesions, and decreased progression of new inflammatory lesions at week 16 ( Figure 1). These results are consistent with those seen in patients with established AS (18,22,29). Additionally, we observed impressive clinical responses to infliximab therapy, with improvement in disease activity, functional status, and quality of life seen at week 16.…”

“…Previous studies in established AS have shown that patients with a shorter disease duration have a better response to anti-TNF agents (30), suggesting that very early treatment before damage is evident on radiographs will lead to improved responses. Therefore, this study confirms the efficacy of infliximab in early axial SpA and suggests that these patients may respond more favorably to infliximab treatment than patients with radiographically evident, established AS (18,22,29).…”

“…The pretreatment and posttreatment scans were scored together simultaneously by 2 independent observers (DM and LCC) who were blinded to both the order of the scans and to treatment group, using a previously reported scoring system (3,22). Observer disagreement was resolved by consensus.…”

“…Regions of MRI-determined sacroiliitis, as defined on T2-weighted fat-suppressed images as bone marrow edema (identified by a high or intermediate marrow signal), were scored. For scoring purposes, the sacroiliiac joint was split into 8 regions, as previously described (22). Briefly, a line was drawn across the upper third of the sacroiliac joint, and the upper right iliac, upper right sacral, upper left sacral, and upper left iliac regions were evaluated.…”

A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis

“…Several clinical studies have shown that etanercept reduces disease activity in patients with spondyloarthropathies, including reactive arthritis and AS [4][5][6][7][8]. Similar results have been reported with inXiximab, a chimeric monoclonal antibody against TNF [9][10][11][12][13][14][15]. The aim of the present work was to compare the eYcacy and safety of both etanercept and inXiximab in patients with ankylosing spondylitis in a two-year open label randomised study.…”