Background/Purpose:

Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are the most common chronic inflammatory joint diseases, with a combined prevalence close to 2%. The pathogenetic role of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα) is now beyond question, with immunohistological studies showing the cytokine and its receptors to be present in inflamed synovial tissue. Nevertheless, there is a large variability in the level of TNFα expression, which may have clinical consequences, since it has been recognized that a subset of patients do not respond to TNFα antagonism. Accurate information on TNFα expression in the joints might be helpful to optimise and/or monitor the effect of TNFα blockade. Scintigraphy with 99mTc-radiolabelled anti-TNFα monoclonal antibodies may offer an exciting possibility for identifying TNF driven disease and predict anti TNF responders in SpA and RA patients in a non-invasive way.

Objectives:

To evaluate the concordance between uptake of Tc99m-labeled certolizumab pegol and peripheral arthritis / dactylitis as assessed by clinical examination and ultrasound (greyscale (GS), power Doppler (PD)) in patients with active RA and peripheral SpA (pSpA).

Methods:

Certolizumab pegol was conjugated with succinimylhydrazinicotinamide (S-HYNIC) and subsequently radiolabeled with Tc99m: patients were injected with 740 MBq, and whole body images and static images of hands and feet were acquired immediately following administration, after 4-6 hours and 24 hours post injection. Prior to the immunoscintigraphy, patients underwent a full rheumatological examination (68-joint count, dactylitis assessment), as well as a targeted ultrasound assessment. Ultrasound and immunoscintigraphic findings were scored semiquantitatively (0: normal, 1: mild, 2: moderate, 3: severe).

Results:

Six patients were included (RA n=3, pSpA n=3). In most of the clinically involved joints of hands and feet a marked tracer uptake was visualized within minutes following injection, with the evaluation 4-6 hours post-injection, yielding the best discriminatory results. In peripheral SpA patients with dactylitis a typical scintigraphic pattern was observed with tracer uptake in both the joints and the accompanying flexor tendon. Concordance results per patient are shown in table 1. Overall, a concordance of approx. 90% was found for ultrasound and swollen joint count.

Table 1

Patient		Concordance scintigraphy vs ultrasound PD	Concordance scintigraphy vs ultrasound GS	Concordance scintigraphy vs tender joints	Concordance scintigraphy vs swollen joints
1	p SpA	91,3%	91,3%	89,1%		91,7%
2	p SpA	100%	100%	98,4%		98,8%
3	p SpA	91,5%	91,5%	87,5%		86,6%
4	RA	80,8%	80,8%	32,3%		78,3%
5	RA	89,3%	89,3%	78,1%		85,5%
6	RA	100%	80,8%	95,2%		98,4%
Overall		92,1%	88,9%	80,1%		89,9%

Conclusion:

In patients with active RA or pSpA, a high concordance rate was observed between Tc99m-labeled certolizumab pegol uptake and clinically or ultrasound detected peripheral arthritis or dactylitis (the latter with a distinct scintigraphic pattern). This technique might provide a possibility to perform ‘evidence-based biological therapy’ by assessing in inflamed joints/tendons the local expression of a target cytokine with a radiolabeled antibody, before using the same cold antibody therapeutically.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/scintigraphic-detection-of-tnf%ce%b1-with-a-radiolabeled-anti-tnf%ce%b1-in-patients-with-active-peripheral-spondyloarthritis-and-rheumatoid-arthritis/