Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial

Abstract

Objective To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone. Methods A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions. Results After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score −2.9 ± 5.1, versus −2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score −4.3 ± 5.2 in the infliximab plus naproxen group versus −3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86]). Conclusion These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti‐TNF.

Impact of Tumor Necrosis Factor Inhibitor Versus Nonsteroidal Antiinflammatory Drug Treatment on Radiographic Progression in Early Ankylosing Spondylitis: Its Relationship to Inflammation Control During Treatment

“…Maksymowych et al showed that advanced inflammatory vertebral corner lesions on magnetic resonance imaging (MRI) are more likely to progress to syndesmophytes through a process of fat metaplasia in spite of TNFi treatment, while early lesions could be resolved without progression . In the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial, which enrolled patients with axial spondyloarthritis of <3 years duration, ~70% of resolved vertebral inflammatory lesions did not progress to new fatty lesions . These results indicate that early, effective antiinflammatory treatment may reduce radiographic progression in AS.…”

Poster Presentation Abstracts

“…In CANADIAN-AS, 9 new bone formation was more apparent in advanced vertebral corner inflammatory legions (CILs) compared with less advanced CILs. In INFAST, 10,11 there was significantly greater reduction in inflammation with combination therapy (infliximab + naproxen) versus naproxen alone. Conclusions: There is evidence that TNF inhibitors may reduce inflammation in the spine and SI joint, and a relationship exists between inflammation presence and new fatty lesion development, as assessed by MRI in axSpA patients.…”

“…Results: Four RCTs were included (Table). [5][6][7][8][9][10][11] In ESTHER, 5 there was a greater increase of fatty lesion score in the etanercept versus the sulfasalazine group. A significant relationship between inflammation disappearance and fatty lesion appearance was noted in etanercepttreated patients.…”

“…10.5%, mixed connective tissue disease (MCTD) 6.0%, overlap syndrome 6.0%, and other diseases 11.7%. Follow-up duration was 31 months (IQR 9-60).…”

Treatment of Axial Spondyloarthritis: What Does the Future Hold?

“…It is believed that their good efficacy is due to their anti-inflammatory capacity, although the exact mechanism why NSAIDs work so well in the treatment of axSpA is still not known. It could also be shown in several studies in AS that NSAIDs can lower C-reactive protein (CRP) [ 7 , 8 ] and in another axSpA study that NSAIDs can reduce inflammation in the axial skeleton as detected by magnetic resonance imaging (MRI) [ 9 ], although the latter study did not include a placebo group.…”