Two years of either triple therapy or treatment with tumor necrosis factor plus methotrexate failed to eliminate joint inflammation on MRI in a subcohort of patients with early rheumatoid arthritis from the randomized, double-blind Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.
In 118 patients with a mean age of 51 years, short disease duration, and severe disease at TEAR trial entry – 92% of whom were seropositive – only 29 had wrist pain, tenderness, or swelling at 2-year follow-up. However, all 118 patients had MRI evidence of residual joint inflammation after 2 years, and 78% had evidence of osteitis, Dr. Veena K. Ranganath of the University of California, Los Angeles, and her colleagues reported (Arthritis Care Res. 2015 Jan. 7 [doi:10.1002/acr.22541]).
Inflammation remained despite significant improvement of disease activity measures at the time of the MRI, compared with baseline (for example, 28-joint disease activity score using erythrocyte sedimentation rate [DAS28-ESR] decreased from 5.8 to 2.9). Total MRI inflammation scores were significantly lower in patients who met 2011 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria and remission by Chronic Disease Activity Index (CDAI), but not in those with DAS28-ESR remission, they noted.
The findings demonstrate that total MRI inflammatory scores are “best differentiated by the most stringent clinical remission criteria” – CDAI and 2011 ACR/EULAR Boolean Criteria, as opposed to DAS28-ESR (with a 2.6 cutpoint). Further, no differences were seen in damage or MRI inflammatory scores based on treatment regimen, which supports methotrexate-first recommendations for the TEAR trial, they said, noting that the long-term prognostic implications of the study findings are unclear because of short-follow-up, and that it remains unclear whether attainment of clinical remission warrants a drug holiday or cessation of RA treatment.
Thus, it is “ill-advised to discontinue therapy until future studies suggest otherwise,” they concluded, adding that this is particularly true given that prior published data suggest a link between osteitis – which occurred at a high rate in this study despite clinical remission – and future radiographic progression.
The TEAR trial was supported by Amgen. The current research was supported by a National Institutes of Health/National Center for Advancing Translational Science UCLA CTSI grant, and individual authors were supported by ACR/REF grants, a National Institutes of Health award, the Margaret J. Miller Endowed Professor of Research Chair, and the Agency for Healthcare Research and Quality.