Etanercept tied to structural improvement in nonradiographic axial spondyloarthritis
The use of the tumour necrosis factor (TNF) inhibitor etanercept was associated with structure-modifying effects (ie, reduction in erosion and increase in backfill) as reflected by MRI scans of the sacroiliac joints (SIJ) of patients with nonradiographic axial spondyloarthritis (nr-axSpA), according to a post hoc analysis of the EMBARK* trial.
Erosion pertains to a breach in the iliac or sacral cortical bone and loss of bright signal from the adjacent bone marrow matrix, whereas backfill signifies the infilling of the eroded cavity bordered by sclerotic bone, said the researchers.
Greater reduction in erosion and increase in backfill was observed with etanercept vs placebo, given the significantly greater change in mean SPARCC SSS** at 12 weeks (-0.57 vs -0.08; p=0.017 and 0.36 vs 0.06; p=0.022 for erosion and backfill, respectively). [Ann Rheum Dis 2018;77:78-84]
Significant treatment difference with etanercept vs placebo was also observed among patients with baseline inflammation on MRI (-0.81 vs -0.13; p=0.007 and 0.48 vs 0.08; p=0.032 for erosion and backfill, respectively).
The resolution of erosion is an indication of new tissue developing at the erosion cavity, while the appearance of backfill at 12 weeks represents a very early reparative response to anti-TNF therapy, said the researchers. [Arthritis Rheumatol 2014;66:2958-2967; J Rheumatol 2015;42:79-86]
Moreover, these modifications correlated with improvements in ASDAS-CRP***, BASDAI#, SPARCC MRI SIJ, and SPARCC spine 23-discovertebral unit scores (for erosion only), which were weak to moderate in strength (Spearman correlation ranging from 0.29–0.51; p<0.01 and −0.40 to −0.26; p<0.05 for erosion and backfill, respectively).
A total of 185 participants with nr-axSpA (BASDAI score ≥4) who had inadequate response to NSAIDs were randomized to receive etanercept 50 mg/week or placebo for 12 weeks (n=88 and 97, respectively), followed by open-label etanercept 50 mg/week. Of these, 82.2 percent were ASAS## MRI sacroiliitis-positive and almost 70 percent had MRI inflammation according to SPARCC BME### score ≥2.
The 12-week treatment effect is a stark improvement from previous evidence demonstrating resolution of erosion and appearance of backfill at 2 years. [Arthritis Res Ther 2014;16:R100] However, another study showed no treatment difference in erosion scores between etanercept and sulfasalazine at 24 weeks, despite the presence of early SpA and more significant radiographic findings at baseline. [Ann Rheum Dis 2011;70:1257-1263]
Despite previous contrasting evidence, the current association found between MRI and clinical parameters is more robust, which could be due to the short symptom duration and/or the significant differences in lesion scoring methodology, noted the researchers. [Ann Rheum Dis 2012;71:2002-2005; Arthritis Res Ther 2014;16:R35]
“[Our findings] support the validity of the MRI feature of backfill as a reparative lesion, because the correlations are negative with several parameters reflecting disease activity that are scored independently from structural lesions,” they said.
These findings also highlight the potential of MRI of the SIJ, which can immediately reveal structural lesions and identify sacroiliitis – a defining feature of nr-axSpA, as a more sensitive endpoint to establish structural modification in nr-axSpA, said the researchers. [Ann Rheum Dis 2006;65:804-808; Arthritis Rheumatol 2014;66:667-673; Arthritis Care Res 2010;62:1763-1771]
A longer-term evaluation on a larger cohort using radiographic endpoints is warranted to further establish the impact of anti-TNF therapy on disease progression in SpA and to better understand the treatment effect of etanercept on new bone formation and maintenance of clinical response beyond 2 years, concluded the researchers.