The Effect of Certolizumab on Lower Extremity Lymph Flow in Rheumatoid Arthritis

Ten RA subjects with unilateral knee synovitis, who have not responded to methotrexate, will be recruited from our early RA Clinics. Following enrollment, the subjects will have a technetium sulfur colloid scan performed on both lower extremities followed by a baseline 3 Tesla contrast-enhanced magnetic resonance imaging (3T CE-MRI) study and Doppler US on the involved knee as described below. The overall disease activity will be determined by the DAS 28 and activity in the involved knee with the RAOS instrument; an outcome measure that quantifies the degree of tenderness, swelling and function in monoarthritis. The subjects will then receive 18 weeks of certolizumab and three of the ten subjects will undergo repeat technetium sulfur colloid scans. To test our hypotheses, we will select three responders based on the RAOS response. We will select only three of the 10 for repeat nuclear studies because this number of subjects will allow us to test our hypothesis without the need to perform the scan on all the subjects. All ten subjects with have 3T CE-MRI, Doppler US and clinical evaluations performed at the 18 week time point. The subjects will continue on certolizumab for a total of 24 weeks.

Sulfur Colloid Technetium Scan. A nuclear radiology technician will inject 0.25cc of technetium sulfur colloid into the first through third web spaces of the feet in both lower extremities. In healthy controls the transit time from the feet to the aortic bifurcation is about 30 minutes. The transit time of the tracer will be measured in both lower extremities at the knee, inguinal ligament and at the aortic bifurcation. Images will be obtained with a nuclear camera according to standard protocol serially over the first hour and delayed images acquired in 4 to 6 hours if necessary. Three subjects who have responded to certolizumab will have the scan repeated at 18 weeks as outlined above.

3T CE-MRI. Two radiologists will independently quantify LN volume and CE of all nodes in the popliteal area from the MRI. These radiologists will also quantify the extent of synovial inflammation, cartilage erosion and bone marrow edema via the RA MRI scoring system (RAMRIS). Consensus findings will be reached and the volume and CE for each node identified together with the RAMRIS will be entered into a database for this study. At the end of the study, we will assess the trend of anti-TNF therapy on:

1. The number of detectable LN in the popliteal fossa
2. Mean LN volume for detectable LN
3. Mean LNCE for detectable LN
4. LNcap for detectable LN
5. RAMRIS, by plotting the change over 8 weeks for each knee independently as we have previously described for anti-TNF effects on bone marrow edema in PsA subjects. The relationship between LN and clinical response to therapy will be assessed from deriving the significance of the correlation coefficient (x2) of LNcap vs DAS28 respectively, as we have done for bone marrow edema vs. DAS28 in PsA subjects on anti-TNF therapy.

Doppler US. Ultrasound examinations of PLN will be obtained at baseline and 18 weeks after anti-TNF therapy as follows. All US examinations will be performed by a rheumatologist (RT) certified in musculoskeletal ultrasound.