Search

To the Editor: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that can be considered as a prothrombotic state1. A great number of studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of this disease. The presence of large amounts of superoxide radicals and hydrogen peroxide produced by activated neutrophils has been reported in the synovial fluid of patients with RA. This may cause lipid peroxidation that yields a wide variety of end products, including malondialdehyde (MDA), a known marker of oxidative stress. These products are therefore transported from the synovial fluid to the blood circulation system2. Considering that elevated levels of MDA have been observed in the blood plasma of patients with RA2, the aim of this pilot study was to investigate whether the elevated levels of plasmatic MDA could be associated with a modification of the total antioxidant capacity (TAC) of blood plasma that is usually indicative of a “systemic” oxidative imbalance3. In addition, in view of their activity as redox effectors or scavengers4, as well as determinants of thrombus formation … Address correspondence to Dr. E. Straface, Istituto Superiore di Sanita, Department of Therapeutic Research and Medicine Evaluation, Section of Cell Aging and Gender Medicine, Viale Regina Elena 299 - 00161 Rome, Italy. E-mail: elisabetta.straface{at}iss.it

Objective.Tumor necrosis factor-α (TNF-α) antagonists bring about significant improvement in chronic inflammatory diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). There is some evidence that they can also have negative myocardial effects, but to date this issue has not been clarified. We evaluated changes in electrocardiographic measures [QT interval, corrected, dispersion, and dispersion corrected (QT, QTc, QTd, QTdc, respectively)] in patients with RA or SpA treated with anti-TNF agents (infliximab and etanercept), those treated with other biological agents (rituximab), and with methotrexate.Methods.We studied 38 consecutive patients with RA (21 patients) or SpA (19 patients) being treated with TNF-α antagonists, 8 patients with RA being treated with rituximab, and 13 patients (8 with RA and 5 with SpA) taking methotrexate. Electrocardiographs (ECG) were performed on all participants at baseline and 12 months after initiation of treatment, and the QT, QTc, and QTd were calculated with standard procedures.Results.After 12 months of treatment, significant increases over baseline values were observed in the mean QT (p < 0.009), QTd (p < 0.0001), and QTdc (p < 0.0001) of the anti-TNF group, but no significant changes were observed in those taking rituximab. QT changes in the anti-TNF group were unrelated to the disease (RA vs SpA) or drug (infliximab vs etanercept), and none were associated with clinical manifestations of cardiac disease.Conclusion.In patients with RA and SpA, TNF-α antagonists seem to increase the QT and QTd measures. Although these changes were completely asymptomatic, ECG may be indicated in patients being considered for anti-TNF therapy to identify those at risk for cardiac complications.

Objective.To assess the performance of serial QuantiFeron-TB Gold In-Tube (QFT-GIT) tests in patients with rheumatic diseases during longterm systemic treatment with biologic therapy, evaluating conversions and reversions in relation to the clinical outcome.Methods.We conducted a prospective study on patients awaiting biologic agents. At baseline, they had chest radiographs, QFT-GIT tests, and tuberculin skin tests (TST); QFT-GIT was repeated at 3, 6, 12, and 18 months after onset of biologic therapy. In patients with no evidence of latent tuberculosis infection (LTBI) at baseline, TST was repeated at 12 months of biologic treatment.Results.Among patients (n = 102; women 65.7%; median age 47 yrs, range 20–82), 14 (13.7%) were considered as having LTBI because of a minimum of 1 abnormal screening test. The agreement between QFT-GIT and TST was 88% (κ = 0.14). During biologic treatment, both patients with (n = 14) and those without (n = 88) evidence of LTBI at baseline showed conversions and reversions in QFT-GIT results at different timepoints. These fluctuations were not paralleled by significant clinical changes. The TST repeated at 12 months in patients with no evidence of LTBI at baseline continued to be negative. The median baseline interferon-γ (IFN-γ) concentration was not significantly different from that observed at each subsequent timepoint.Conclusion.Dynamic changes occur with serial IFN-γ release assay testing in patients treated with biologic therapy that do not correlate with clinical outcome. A careful and integrated evaluation of the patient, including clinical information, should guide the treatment decision. This study was underpowered for definite conclusions and further studies are needed to determine the significance of these findings.