Effects of Anti-Tumor Necrosis Factor Therapy on Osteoblastic Activity at Sites of Inflammatory and Structural Lesions in Radiographic Axial Spondyloarthritis: A Prospective Proof-of-Concept Study Using Positron Emission Tomography/Magnetic Resonance Imaging of the Sacroiliac Joints and Spine

Objective Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF (F-18-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). Methods Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo F-18-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and F-18-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. Results Overall, 11 male and 5 female patients (mean age +/- SD 38.6 +/- 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). F-18-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, F-18-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less F-18-NaF uptake, compared with baseline. For VCs, F-18-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less F-18-NaF uptake, compared with baseline. Conclusion Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA.