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OP0097 Immunoscintigraphic Detection of TNF by Radiolabeled Certolizumab Pegol in Patients with Erosive Hand Osteoarthritis in Relation To Disease Activity and Structural Progression: A Proof of Concept Study
  1. R. Wittoek1,
  2. P. Carron1,
  3. B. Lambert2,
  4. P. Meersseman1,
  5. A. Verbruggen1,
  6. F. Van den Bosch1,
  7. D. Elewaut1
  1. 1Department of Rheumatology, Ghent University Hospital
  2. 2Department of Radiology and Nuclear Medicine, Ghent University, Ghent, Belgium

Abstract

Background A recent randomized clinical trial in erosive osteoarthritis (EOA) of finger joints with a TNF blocking agent, adalimumab, showed inhibition of radiographic progression in joints showing inflammatory signs (palpable swelling) at baseline (1). We anticipate the use of radio-labelled antibodies can help in identifying their in vivo abundance in joints (2) and might help to identify joints at particular risk for progression amenable for target therapies.

Objectives To investigate the uptake of radiolabeled 99mTc-certolizumab pegol in patients with EOA and study associations with other markers of active disease, including radiography, clinical examination and ultrasound (US).

Methods Certolizumab Pegol was conjugated with S-HYNIC and radiolabeled with Tc99m. At baseline, static images of both hands of 5 patients with EOA (F/M: 4/1; median disease duration 8.4 years; median age 55.6 years) were acquired at 2 time points (immediately following administration (early phase) and after 4–6 hours post injection (late phase)). All 18 IP finger joints were scored according to the anatomical phase scoring system (3) on Xrays. All patients underwent clinical examination (presence of tenderness and palpable swelling of the joints) and Gray-scale and Power Doppler (PD) US one day prior to scintigraphy. Immunoscintigraphic findings were independently scored in a semi-quantitative way (uptake: 0 = absent, 1 = weak; 2 = strong). Descriptive statistics on joint level were calculated. Likelihood ratio (LR) for uptake in late phase was calculated in respect to tenderness, swelling, US and radiographic features (resp. with no tenderness, no swelling, no inflammatory US sign and normal phase as reference).

Results In total, 90 IP joints were studied. Active tracer uptake was seen in 7 joints in early phase (7.8%) (all weak) and in at least 24 joints in late phase (26.7%) (19 weak, 5 strong). No uptake was seen in MCP joints.

Early and late uptake were present in 5 (15.2%) and 12 (36.4%) of 33 tender joints and in resp. 2 (3.5%) and 12 (21.1%) of 57 non-tender joints (LR =2.2, p = NS).

Interestingly, this relation was most pronounced with palpable joint swelling: early and late uptake were present in 5 (21.7%) and 14 (61.0%) of 23 swollen joints and in resp. 2 (3.0%) and 10 (14.9%) of 67 non-swollen joints (LR =8.9, p<0.001).

Early and late uptake were present in resp. 6 (9.7%) and 18 (29.1%) of 62 sonographic active joints (= any presence of effusion or PD signal or synovial proliferation) and in resp. 1 (3.6%) and 6 (21.4%) non-inflammatory joints (LR =1.5, p = NS).

Immunoscintigraphic uptake was observed in all anatomical phases (i.e. N, S, J, E or R) but the strongest association was found with R phase (LR =1.86 with “N” as reference).

Conclusions This is the first in vivo demonstration of TNF abundance in EOA. We found strong associations of certolizumab uptake with presence of swelling of the affected joints. The strongest association with TNF was found in the remodeling phases of the disease. These data further solidify the rationale for cytokine directed therapies in EOA.

  1. Verbruggen G. et al. ARD 2012;71(6):891–8

  2. Barrera P. et al. ARD 2003;62:825–8

  3. Verbruggen G. and Veys E. A&R 1996;39(2):308–20

Disclosure of Interest None declared

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