Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation.

OBJECTIVES: To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). METHODS: Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. RESULTS: At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 (p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. CONCLUSIONS: While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved.

Mitral valve repair is durable in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) and its treatments are associated with tissue abnormalities, which may influence surgical outcomes of repair for severe mitral valve regurgitation (MR). We examined late survival and durability of mitral valve repair in patients with RA. METHODS: Thirty-six patients with RA (21 male) underwent mitral valve repair for MR from August 1978 to August 2005. Median age was 70 years (range, 22 to 84). Preoperatively, 27 patients (75%) had New York Heart Association Functional Class III/IV symptoms, and 29 (78%) required immunomodulating medications for RA management. Mechanisms of MR were leaflet prolapse in 26 patients (72%), leaflet malcoaptation in 5 (14%), tethering in 4 (11%), and unknown in 1 (3%). RESULTS: All patients underwent mitral valve repair, which included posterior leaflet triangular resection in 11 patients, leaflet plication in 10, and artificial chordae placement in 3. When compared with matched control patients without RA who underwent mitral valve repair, RA patients had decreased survival (27% versus 64%, p=0.005) and freedom from reoperation (93% versus 98%, p=0.04) at 8 years. However, RA patients undergoing mitral valve repair had similar survival at 5 years compared with age- and sex-matched comparator patients with RA who did not undergo mitral valve surgery (65% versus 67%, p=nonsignificant). CONCLUSIONS: Mitral leaflet pathology in RA patients with severe MR is similar to that of non-RA patients with mitral valve disease. Long-term survival after mitral valve repair in RA patients is equivalent to that of the general RA population without mitral valve disease, and the durability of mitral valve repair in these patients is very good.