Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

Philippe Carron, Bieke Lambert, Liesbet Van Praet, Filip De Vos, Gaëlle Varkas, Lennart Jans, Dirk Elewaut, Filip Van den Bosch, Philippe Carron, Bieke Lambert, Liesbet Van Praet, Filip De Vos, Gaëlle Varkas, Lennart Jans, Dirk Elewaut, Filip Van den Bosch

Abstract

Background: Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more 'evidence-based biological therapy'.

Objectives: Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome.

Methods: CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP.

Results: In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04).

Conclusions: Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response.

Trial registration number: NCT01590966; Results.

Keywords: Magnetic Resonance Imaging; Rheumatoid Arthritis; Spondyloarthritis; TNF-alpha; Ultrasonography.

Figures

Figure 1
Figure 1
Distribution of Tc99m-radiolabelled certolizumab pegol in hands, feet and SIJs 4–5 hours postinjection. (A) A typical polyarticular pattern of hand and feet joints without distal interphalangeal joint (DIP) involvement was seen in a patient with active rheumatoid arthritis. (B) Distal interphalangeal joint uptake of the left second digit in a patient with polyarticular psoriatic arthritis. (C) Tracer uptake in both the joints and the accompanying flexor tendon in a patient with clinically dactylitis of the fourth digit at the right side. (D) SPECT-CT of the right foot in a patient with spondyloarthritis with enthesitis of the Achilles tendon. (E) Fusion of MRI and SPECT image of the sacroiliac joints of a patient with axial spondyloarthritis. SPECT, single photon emission tomography.
Figure 2
Figure 2
Relationships between the baseline disease activity scores and scintigraphic sum scores for the patients with RA, pSpA and axSpA. ASDAS, Ankylosing Spondylitis Disease Activity Score; axSpA, axial spondyloarthritis; DAS28, Disease Activity Score in 28 joints; pSpA, peripheral spondyloarthritis; RA, rheumatoid arthritis; SPARCC, the Spondyloarthritis Research Consortium of Canada scoring system.

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