Background/Purpose:   A recent randomized clinical trial in erosive osteoarthritis (OA) of finger joints with a TNF blocking agent, adalimumab, showed inhibition of radiographic progression in joints showing inflammatory signs (soft tissue 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. The purpose of the current study is to investigate the uptake of radiolabeled Certolizumab pegol in patients with erosive OA and study associations with other markers of active disease.

Methods:   Certolizumab Pegol was conjugated with S-HYNIC and radiolabeled with ^99mTc. At baseline, static images of both hands of 5 patients with EOA (F/M: 4/1; median disease duration 8.4 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 hand radiographs. All patients underwent clinical examination (presence of tenderness and swelling) 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. Associations between uptake and other signs of disease activity, being presence of tenderness, soft tissue swelling and sonographic activity were calculated by Odds ratios (OR) (with 95% confidence intervals (95% CI)) with absence of tenderness/soft tissue swelling/sonographic activity 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). Considerably more uptake was present in joints with soft tissue swelling compared to non-swollen joints: in 14 (61.0%) of 23 swollen joints and in 10 (14.9%) of 67 non-swollen joints. Presence of soft tissue swelling is found to be significantly associated with uptake with OR = 8.9 (95% C.I. = 3.0 – 26.0). A trend towards more uptake in tender joints was seen compared to non-tender joints (OR = 2.1 (95% C.I = 0.8 -5.6). Similarly, a trend towards more uptake in sonographic active joints was seen (OR = 1.5 (95% C.I. = 0.5 -4.3)).

Conclusion:   This is the first in vivo demonstration of TNF abundance in erosive OA. We found strong associations with presence of clinical swelling. The strongest association with TNF was found in the remodeling phases. These data further solidify the rationale for cytokine directed therapies in EOA. References: (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

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunoscintigraphic-detection-of-tumor-necrosis-factor-by-radiolabeled-certolizumab-pegol-in-patients-with-erosive-hand-osteoarthritis-in-relation-to-disease-activity-a-proof-of-concept-study/