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Autoantibodies in rheumatoid arthritis patients treated with infliximab and methotrexate : one year follow up

It is well known that anti-TNF-alfa treatment can induce occurrence of autoantibodies (AA) in rheumatoid arthritis (RA) patients. In the majority of treated patients they have no clinical significance although several cases of drug induced lupus (DIL) have been described. In almost half of the cases published antinuclear antibodies (ANA) were positive before treatment or unavailable. In some of the published reports patients had previous symptoms which suggest incomplete lupus. Objectives were to evaluate frequency and clinical significance of autoantibodies in RA patients treated with infliximab and methotrexate (MTX) in one year period. 24 patients with active RA, despite therapy with MTX, were treated with MTX and infliximab for one year. The dosage of infliximab was 3mg/kg given week 0, 2, 6 and every 8th week thereafter. Dosage of MTX were 7.5-17.5 mg weekly. All patients were on steroids. Analyses for antinuclear antibodies (ANA), anti-doble-stranded DNA antibodies(anti-ds-DNA), antibodies to extractable nuclear antigen (ENA) and anticardiolipin antibodies (ACLA) were performed at the baseline, at week 2, 6, 14, 22, 30, 38, 46 and 54. Anti-ds-DNA, ENA and ACLA were done by ELISA. At the baseline visit 3/24(12.5%) patients had positive ANA. After nine therapies, at weeek 54 13/17(76.47%) had positive ANA. Maximum titer was 1:4096. Before treatment no patients had anti-ds-DNA. At week 54 10/17(58.82%) were anti-ds-DNA positive(see table). The anti-ds-DNA range between 62-236 U/ml. There were no significant changes in ACLA value. One of our ANA negative patients who has RA established for 19 years, documented by X-ray, developed clinical (worsening of arthritis, pleural effusion and photosensitive rash) and laboratory (ANA 1:320, anti-ds-DNA 64.6 and low C3 and C4) signs of systemic lupus erythematodes (SLE) after 4th infusion. Since her condition improved after infliximab was stopped, diagnosis of DIL was reasonable. One year later she still had positive ANA and anti-ds-DNA as well as photosensitive face rash which suggests a SLE-RA overlaping unmasked by infliximab. In all other patients we could not find any connection between occurrence of autoantibodies and clinical conditions. Reasons for exclusion were allergic reactions (2 patients), lack of efficacy (1 patient) and bad compliance (1 patient). Week 0 Week 2 Week 6 Week 22 Week 46 Week 54 ANA 3/24 5/24 5/23 12/20 13/17 13/17 anti ds DNA 0/24 1/24 1/23 6/20 7/17 10/17 ENA 0/24 0/24 2/23 4/20 5/17 5/17 ACLA 3/24 3/24 3/23 3/20 3/17 3/17 ld]. A high number of our patients developed antinuclear and anti-ds-DNA antibodies during one year treatment with infliximab. Only one patient developed the condition which can be surely connected with occurrence of ANA and anti-ds-DNA induced by infliximab. Although the diagnosis of DIL was reasonable, further monitoring of the patient presumes SLE-RA overlaping unmasked by infliximab. This is a possibility clinicians should be aware of.

rheumatoid arthritis; autoantibodies; infliximab; treatment; SLE

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