Rheumatoid Arthritis: Vis M

Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF. · Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #16606653 No free full text.

Abstract: OBJECTIVES: To examine whether treatment with anti-tumour necrosis factor (TNF) alpha prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment. PATIENTS AND METHODS: 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, beta-isomerised carboxy terminal telopeptide of type 1 collagen (beta-CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks. RESULTS: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum beta-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in beta-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0-14 weeks interval. CONCLUSION: In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands.

Bos WH, Bartelds GM, Vis M, van der Horst AR, Wolbink GJ, van de Stadt RJ, van Schaardenburg D, Dijkmans BA, Lems WF, Nurmohamed MT, Aarden L, Hamann D. · Sanquin Research, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #18445623 No free full text.

Abstract: OBJECTIVE: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks. RESULTS: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4 : IgG1 ACF ratio in the infliximab cohort. In adalimumab-treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4 : IgG1 ratio was reduced by 24% (all percentage values p<0.05). The decrease in antibody levels was correlated with the clinical response; European League Against Rheumatism good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4 : IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels. CONCLUSION: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4 : IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.

Vis M, Bos WH, Wolbink G, Voskuyl AE, Twisk JW, Van de Stadt R, Hamann D, Dijkmans BA, Lems WF. · VU University Medical Center, Sanquin Research, and Jan van Breemen Institute, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #18322974 No free full text.

Abstract: OBJECTIVE: To investigate the effect of treatment with infliximab on serum levels of rheumatoid factor (IgM-RF), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against deiminated human fibrinogen, a specific citrullinated peptide (ACF), and their association with disease activity and disease duration in patients with rheumatoid arthritis (RA). METHODS: The study sample included 62 consecutive patients who were treated with infliximab for at least one year. IgM-RF, anti-CCP, and ACF were measured at 0, 14, 30, and 46 weeks. RESULTS: Patients had a mean age of 54 years and median disease duration of 10 years and were predominantly female (81%). At baseline 63%, 77%, and 82% of patients were positive for IgM-RF, anti-CCP, and ACF, respectively. In terms of percentages, the levels of IgM-RF were reduced by 64% at 46 weeks, while anti-CCP and ACF levels were reduced by roughly 25%. The decrease in serum levels of these autoantibodies was not associated with the decrease in disease activity. The change in ACF was significantly related to disease duration, while the changes in IgM-RF or anti-CCP were not. CONCLUSION: In a cohort of patients with RA who responded to infliximab therapy, all autoantibodies decreased significantly, but IgM-RF showed a larger decrease than anti-CCP or ACF. These changes in levels of autoantibodies are not directly related to the change in disease activity. Early in the disease, ACF levels were best influenced by treatment with infliximab.

Peters MJ, Vis M, van Halm VP, Wolbink GJ, Voskuyl AE, Lems WF, Dijkmans BA, Twisk JW, de Koning MH, van de Stadt RJ, Nurmohamed MT. · Department of Rheumatology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #17314120 No free full text.

Abstract: OBJECTIVE: To evaluate the effects of infliximab and corticosteroid treatment on the lipid profile in patients with active rheumatoid arthritis (RA). METHODS: Infliximab infusions were given at weeks 0, 2, 6 and then every 8 weeks. Before each infusion, disease activity parameters (Disease Activity Index 28-Joint Score (DAS28)) C reactive protein (CRP) and lipid levels (total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B) were measured in 80 consecutive patients with RA, who completed the study period of 48 weeks. Longitudinal analyses were used to investigate (1) the course of lipid levels over a period of time and (2) the relationship between lipids, prednisone dose and disease activity. RESULTS: Infliximab treatment causes a significant reduction in disease activity and a concomitant decrease in prednisone dose. Although they initially improved significantly, all lipid levels had returned to baseline levels after 48 weeks, except for apo A1. Longitudinal analyses revealed significant yet opposite associations between lipid levels and disease activity and between lipid levels and prednisone dose. DAS28 improvement by 1 point was associated with an increase of 0.016 mmol/l (0.618 mg/dl) total cholesterol and 0.045 mmol/l (1.737 mg/dl) HDL-cholesterol. Reduction of 10 mg prednisone was associated with a decrease of 0.04 mmol/l (1.544 mg/dl) total cholesterol and 0.16 mmol/l (6.177 mg/dl) HDL-cholesterol. CONCLUSION: Overall, no changes in serum lipid levels were observed after 48 weeks of infliximab treatment. The initial beneficial effects of infliximab on the lipid profile, by means of a reduction of disease activity, are attenuated by a concomitant decrease in prednisone dose.

Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT, Stapel S, Tak PP, Aarden L, Dijkmans B. · Department of Immunopathology, CLB Sanquin Amsterdam and Jan van Breeman Institute, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #16508927 links to  free full text

Abstract: OBJECTIVE: Treatment of patients with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, may result in the formation of infliximab-specific IgG antibodies. This study evaluated the clinical significance of these antibodies in patients with rheumatoid arthritis (RA). METHODS: Antiinfliximab antibodies were measured using a newly developed radioimmunoassay in a cohort of 51 consecutive patients with RA treated with infliximab, with a followup of 1 year. In addition, serum infliximab levels were determined by enzyme-linked immunosorbent assay. The results were analyzed in relation to the clinical response to treatment according to the European League Against Rheumatism criteria. RESULTS: Antibodies against infliximab were detected in 22 patients (43%). Patients without detectable antiinfliximab antibodies (n = 29 [57%]) were significantly more often classified as responders (20 of 29 [69%]) compared with patients with detectable antiinfliximab antibodies (8 of 22 [36%]; P = 0.04). Three patients had an infusion-related allergic reaction, all of whom had detectable antiinfliximab antibodies. CONCLUSION: In this study, nearly half of the RA patients treated with infliximab developed antiinfliximab antibodies within the first year of treatment. This seems to be clinically relevant, since development of antiinfliximab antibodies is associated with a reduced response to treatment.

Vis M, Nurmohamed MT, Wolbink G, Voskuyl AE, de Koning M, van de Stadt R, Twisk JW, Dijkmans BA, Lems WF. · Department of Rheumatology, VU University Medical Centre, Jan van Breemen Institute, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #15693084 No free full text.

Abstract: OBJECTIVE: Cardiovascular morbidity and mortality appear to be enhanced in rheumatoid arthritis (RA), which might be due to an increased prevalence of cardiovascular risk factors such as dyslipidemia. It was recently shown that effective disease modifying antirheumatic drug treatment had a favorable influence on the lipid profile in patients with active RA. As infliximab markedly reduces disease activity in RA, we investigated the effects of infliximab on the lipid profile. METHODS: Infliximab was administered at baseline and at 2 and 6 weeks in patients with active RA. Total cholesterol and HDL-cholesterol concentrations were measured and their ratio, the atherogenic index (an important cardiovascular risk factor indicator), was assessed. RESULTS: Sixty-nine patients were enrolled. The Disease Activity Index score (DAS-28) was 5.9 (SD +/- 1.4) at baseline and decreased to 4.6 (+/- 1.4) after 2 weeks and further to 4.1 (+/- 1.5) after 6 weeks. Total cholesterol level was 5.2 mmol/l at baseline and increased to 5.7 mmol/l (p < 0.001) at 2 weeks, and was 5.6 mmol/l (p < 0.001 vs baseline) at Week 6. For HDL-cholesterol these values were 1.5, 1.6 (p < 0.001), and 1.6 mmol/l (p < 0.001 vs baseline), respectively. Changes in disease activity were significantly inversely associated with changes in total cholesterol and HDL-cholesterol levels. The atherogenic index, however, remained constant. Corticosteroid use at baseline was associated with significantly higher total cholesterol and HDL-cholesterol levels and a lower (more favorable) atherogenic index at baseline. CONCLUSION: Infliximab treatment was associated with a significant increase of both total cholesterol and HDL-cholesterol levels, which correlated with decreasing disease activity. However, this was not accompanied by a favorable effect on the atherogenic index. The favorable effect of infliximab on cardiovascular comorbidity might not be mediated by effects on lipid metabolism, but longterm investigations are needed to confirm this.

Vis M, Voskuyl AE, Wolbink GJ, Dijkmans BA, Lems WF, Anonymous00146. · No affiliation provided · Ann Rheum Dis. · Pubmed #15647447 links to  free full text

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Neven N, Vis M, Voskuyl AE, Wolbink GJ, Nurmohamed MT, Dijkmans BA, Lems WF. · No affiliation provided · Ann Rheum Dis. · Pubmed #15769924 links to  free full text

This publication has no abstract.

Vis M, Wolbink GJ, Lodder MC, Kostense PJ, van de Stadt RJ, de Koning MH, Dijkmans BA, Lems WF. · No affiliation provided · Arthritis Rheum. · Pubmed #14558111 links to  free full text

This publication has no abstract.