RA TNF Antagonists
Abstract 1311: Delay in Imaging Versus Clinical Response Provides Rationale for Prolonged Treatment with Anti-TNF in Early Rheumatoid Arthritis
AUTHORS: RJ Wakefield, JE Freeston, EMA Hensor, D Bryer, MA Quinn, P Emery
BACKGROUND: The efficacy of RA therapy is often judged in terms of physician derived measurements such as the evaluation of swollen and tender joints. We are now able to see patients treated with more aggressive treatment approaches with TNF Antagonists and other biological agents with remission as measured by DAS and even with responses approaching complete clinical responses/clinical remission (CR) with no evidence of swollen and tender joints. The use of more sensitive methods of assessment of joints using MRI and ultrasound (USG) imaging however are revealing the present of ongoing disease. Defining a new endpoint of an imaging remission (IR) thus becomes possible, yet this has not been well explored.
METHODS: This was a small pilot study of 10 DMARD naïve, early RA patients who were treated with infliximab (IFX) 3 mg/kg and rapidly escalated methotrexate (MTX) to 20 mg/wk by 6 weeks. USG examinations with Gray Scale (GS) and power Doppler (PD) were performed of 42 joints prior to infusions at with individual joints scored using a semi-quantitative scoring (0-3) method. Clinical assessments included metrology (DAS 28), and laboratory tests (CRP). CR was defined as a DAS28 < 2.6 and IR as both a GS and PD score of 0. Clinical response was defined as a decrease in DAS28 score of > 1.2.
RESULTS: 10 patients were recruited with median age 52.5 yr, disease duration 6 months, 80% RF positive and median DAS28 6.02. At week 0, 64% of joints had GS synovitis and 33% had PD synovitis. GS scores were higher than PD scores in each patient. Nine patients had achieved CR by a median 14 weeks; however, none of these patients were in IR with 53% of joints demonstrating GS synovitis and 20% with PD synovitis. Synovitis detected by US fell steadily, beginning to plateau at 22 weeks, when 40% joints had GS synovitis and 8% PD synovitis.
CONCLUSIONS: This pilot study of early RA patients treated aggressively with IFX and MTX showed that CR is achieved before IR. After CR was reached, synovitis detected by imaging continued to fall and only later begin to plateau, but rarely returning to zero. True imaging remission was not demonstrated due to residual low background synovitis.
EDITORIAL COMMENT: This is a very intriguing study albeit of only a small number of patients demonstrating that ultrasound detectable synovitis persists even when patients are in clinical remission based on DAS scores. Thus the decision to stop therapy based on a clinical response is questioned when using a more sensitive method of assessing “activity”. Whether these patients truly had zero swollen and tender joints was unclear, but would have been a more appropriate standard against which to judge the imaging remission. The same group reported at ACR last year that ultrasound and MRI detectable synovitis are frequently found in many patients with true clinical remission (with zero swollen and tender joints). These data support additional research to determine the time course of improvement seen with ultrasound and will require validation against other imaging modalities including MRI and plain radiography. Whether a true imaging remission can be achieved remains to be seen or whether the findings that persist with ultrasound are necessarily relevant to longer term outcomes or joint destruction also needs to be determined.
