ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1978

The Effect Of Certolizumab On Lymphatic Volume and Flow In Rheumatoid Arthritis Patients With Acute Flare

Homaira Rahimi1, Vaseem Chengazi2, Gregory Dieudonne2, Edward M. Schwarz3 and Christopher T. Ritchlin4, 1Pediatrics, University of Rochester, Rochester, NY, 2Radiology, University of Rochester, Rochester, NY, 3Center for Musculoskeletal Research, University of Rochester, Rochester, NY, 4Allergy, Immunology and Rheumatology, University of Rochester, Rochester, NY

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , , , ,

Session Information

Title: Imaging in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Episodic flare occurs in rheumatoid arthritis (RA) but the mechanisms of this process are not well understood. Our prior reports on MRI analysis of joints in murine arthritis models showed expanded volume and increased contrast enhancement in the popliteal node draining inflamed knees prior to arthritic flare. In the expanded node, B cells translocate to paracortical sinuses, the node suddenly collapses and there is loss of efferent lymphatic drainage and rapid onset of synovitis. Two models of flare dependent on disease duration were identified. In acute flare, joint inflammation overwhelms the lymphatics and can be effectively treated with anti-inflammatories (i.e. anti-TNF). However, mice with chronic arthritis that flare lack an efferent lymphatic pulse and are unable to normalize lymphatic function or mediate arthritic flare. To examine if similar lymph node (LN) volume and lymphatic function is altered in adult RA patients, we performed MRIs of affected joints and LN and measured lymphatic flow in RA patients with acute flare, before and after certolizumab therapy. Methods: Eight RA patients with active flare of a single wrist or knee underwent 3T pre and post contrast MRIs at baseline and 18 weeks after certolizumab. LN volumes of the popliteal or epitrochlear nodes were quantified. A subset of 3 patients underwent radiocolloid Technetium sulfur tracing (RTS) to assess lymphatic flow in the affected and unaffected extremity. RTS studies were read by a radiologist blinded to the extremity with joint flare. Results:  Of eight patients, all had improvement in disease activity score (DAS) and all six of eight with LN noted on MRI had alterations of total LN volume (Table 1.) Of those six patients, all but one had a decrease in total LN volume. Three patients underwent RTS and MRI.  Patient 1 had foot- inguinal transit time (tt) of 15min to the affected extremity that increased after treatment to 65min (normal tt is 60min), showing normalization of lymphatic flow after treatment. Patient 2 had foot -inguinal tt of 15min to the affected extremity that increased after treatment to 24min, showing deceleration in lymphatic flow. Patient 7 had long standing disease and markedly decreased lymphatic flow (hand-axillary tt >75 min, normal tt is 30min) prior to treatment that did not change with therapy; no nodes were visible on MRI pre or post treatment. Conclusion: LN volume and lymphatic flow are altered in response to anti-TNF therapy. Specifically, total LN volume decreased with certolizumab and patients with shorter disease duration appear to improve lymphatic flow, whereas patients with long-standing disease may not normalize lymphatic flow. Thus, similar to murine inflammatory arthritis, there may be an early versus chronic model of arthritic flare in which lymphatic function is a key factor and treatment response may depend on how severely lymphatic function is compromised. 

Table 1

Disclosure:

H. Rahimi,
None;

V. Chengazi,
None;

G. Dieudonne,
None;

E. M. Schwarz,
None;

C. T. Ritchlin,

Amgen, Janssen, UCB, Abbott (AbbVie), Regeneron,

5,

Amgen, Janssen, UCB,

2.

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