Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.

OBJECTIVES: The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. RESULTS: At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. CONCLUSIONS: We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.

The effects of biologic agents on cardiovascular risk factors and atherosclerosis in rheumatoid arthritis patients: a prospective observational study.

We aimed to evaluate the impact of biologic treatment on subclinical atherosclerosis and risk factors for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Forty-nine biologic naïve RA patients, treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), who were eligible for treatment with a biologic agent, were included in the study. The serum levels of lipid parameters, as well as disease activity parameters were determined in RA patients before and after 3 and 6 months of therapy. Carotid artery intima-media thickness (cIMT) was measured before and after treatment. A comparison analysis of change of these parameters was also performed between anti-tumor necrosis factor (anti-TNF) and non-anti-TNF users. Furthermore, 31 non-smoking healthy volunteers, matched for age and gender, were used as a control group. At baseline, RA patients had a decrease in serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels compared with controls (209 ± 63 vs 233 ± 44 and 58 ± 15 vs 61 ± 14, p < 0.004), while cIMT was higher versus controls [0.9 (0.8-1) vs 0.6 (0.5-0.7), p < 0.001]. TC, HDL-C and apolipoprotein A1 levels were significantly increased 3 months after treatment (209 ± 63, 58 ± 15, 162 ± 32, vs 227 ± 45, 60 ± 15, 169 ± 29, respectively, p < 0.03) and this observation remained stable at a 6-month follow-up. After 6 months, there was also a statistically significant decrease in the cIMT [0.9 (0.8-1) vs 0.7 (0.6-0.8), p < 0.001]. Anti-TNF and non-anti-TNF users had comparable changes in cardiovascular risk parameters. The atherogenic lipid profile and subclinical atherosclerosis are features of RA, which appeared improved after biologic therapy initiation.

Certolizumab for rheumatoid arthritis.

This is a review of the pharmacology of certolizumab pegol and its efficacy and safety in the treatment of patients with rheumatoid arthritis refractory to synthetic disease-modifying anti-rheumatic drugs (DMARDs). Certolizumab is a new anti-TNF-α biologic agent injected subcutaneously with an innovative molecular structure and unique pharmacodynamic and pharmacokinetic properties. Data from controlled clinical trials indicate that the drug is effective in reducing disease activity and disability. It also inhibits radiographic progression. Certolizumab administration has an acceptable safety profile. The clinical data available suggest that the nature of adverse events is generally comparable to that of other TNF-α blockers. Given its rapid onset of action certolizumab presents an attractive alternative therapeutic option for patients with moderate to severe RA refractory to DMARDs.

Survival of TNF-alpha antagonists in rheumatoid arthritis: a long-term study.

OBJECTIVES: To investigate the efficacy, safety and survival of tumour necrosis factor (TNF) α antagonists in patients with rheumatoid arthritis (RA). METHODS: One hundred and fifty-one RA patients treated with TNF-α inhibitors during the time period 2000 to 2009 were studied. Kaplan-Meier statistic analysis was applied, in which discontinuation from anti-TNF-α therapy was used as the terminal event. RESULTS: Eighty-two patients received infliximab, 49 adalimumab and 20 etanercept: they were followed up over 7, 5 and 4 years, respectively. Anti-TNF-α therapy resulted in a rapid clinical improvement associated with a reduction in inflammatory markers in the first year of the treatment, which was sustained throughout the following years. Ninety (59.6%) patients were withdrawn during the observational period overall. The patients who discontinued infliximab, adalimumab and etanercept therapy were 55/82 (67.1%), 27/49 (55.1%) and 8/20 (40%) respectively. The main reasons for discontinuation were drug adverse events and inefficacy. According to Kaplan-Meier methods, the 'survival rate' of infliximab after the first year of treatment reached 82.9%, while after 7 years the proportion was 32.9%. With regard to adalimumab, after the first year of treatment its 'survival rate' was 83.7% and after 5 years it reached 44.9%. As far as etanercept is concerned, after the first year of treatment, the 'survival rate' reached 70% and after 4 years it remained 60%. CONCLUSIONS: TNF-α antagonists constitute an effective therapeutic option for patients with RA refractory to disease-modifying anti-rheumatic drugs. They demonstrate an acceptable safety profile. Their survival rate is high in the first years of treatment, while after the fifth year it decreases considerably.

Prognostic factors for erosive rheumatoid arthritis.

The course of rheumatoid arthritis (RA) varies among patients, ranging from a mild disease with a small impact on patient's functional capacity to a severe, erosive and catastrophic disease accompanied by subluxations, deformities and subsequent poor quality of life. In clinical practice, the prediction of the outcome of RA is substantial in terms of making the right therapeutic decision for each patient. Reliable prognostic factors of long-term outcome are needed, so as to distinguish patients prone to severe disease course from patients with a smaller probability of severe structural damage. For the former group early aggressive treatment is required, whereas in the latter group remission may be achieved with less aggressive and potentially less toxic treatments. In the present review, the predictive role of demographic, clinical, laboratory, imaging, immunological and genetic characteristics of RA patients is discussed.

Immune-mediated skin lesions in patients treated with anti-tumour necrosis factor alpha inhibitors.

OBJECTIVE: To describe immune-mediated skin lesion (IMSL) development in patients during anti-tumour necrosis factor (TNF) therapy. METHODS: Two hundred and fifty-two patients with rheumatoid arthritis (RA) and 183 with spondyloarthropathies (SpA) treated with anti-TNF inhibitors were analysed to identify IMSLs. RESULTS: Of the 252 patients with RA (146 treated with infliximab, 72 with adalimumab, and 34 with etanercept), 32 developed IMSLs. Eleven patients developed psoriatic skin lesions, 10 presented with granuloma annulare (GA), five had skin vasculitis, two alopecia areata, two discoid lupus erythematosus, one lichenoid eruption (lichen planus), and one vitiligo. Of the 183 patients with SpA (138 treated with infliximab, 37 with etanercept, and eight with adalimumab), 10 cases with IMSLs were identified. All were treated with infliximab. More specifically, six patients with ankylosing spondylitis (AS) developed psoriatic skin lesions, one developed GA, one lichen planus, and one alopecia areata. In addition, one patient with psoriatic arthritis (PsA) developed skin vasculitis. The occurrence of these IMSLs ranged from 3 to 36 months with a median of 20 months. Of all the patients with IMSL development, two with psoriatic skin lesions, two with GA, and one with vasculitis stopped anti-TNF therapy because of the extent and severity of the skin lesions. CONCLUSIONS: Our results on patients treated with TNF antagonists strongly support a link between TNF inhibition and IMSL development. Although these clinical complications are rare, clinicians should be aware of their occurrence and should recognize them.

Induction of psoriatic skin lesions in a patient with rheumatoid arthritis treated with rituximab.

Rituximab is a chimeric monoclonal therapeutic antibody which causes depletion of CD20-positive B cells. Apart from its apparent efficacy in the treatment of non-Hodgkin lymphoma and of several rheumatic diseases, it is associated with adverse events including the induction of autoimmune phenomena. We describe here the development of psoriatic skin lesions in a patient with rheumatoid arthritis after the second course of treatment with rituximab. This report supports the hypothesis that autoimmune phenomena may occur by biologic agents and there is a link between B-cell depletion and the induction of psoriatic skin lesions, which were confirmed histologically. However, further studies are needed in order to identify the underlying mechanism, as well as the risk factors associated with rituximab-induced psoriatic skin lesions.

Granuloma annulare induced by anti-tumour necrosis factor therapy.

OBJECTIVE: To describe granuloma annulare (GA) skin lesion development in patients during anti-tumour necrosis factor (TNF) therapy. METHODS: 199 patients with rheumatoid arthritis and 127 suffering from spondyloarthropathies treated with anti-TNF antagonists were analysed to identify skin lesions suggesting GA. RESULTS: Nine cases of GA during anti-TNF therapy (123 treated with infliximab, 57 with adalimumab and 17 with etanercept) for rheumatoid arthritis were identified. Two have been treated with infliximab, six with adalimumab and one with etanercept, and here the development of GA was 4.5%. No patient with spondyloarthropathies developed such skin lesions. All patients developed the generalised form of GA. None had or developed diseases, or conditions known to be associated with GA. In seven patients the skin eruptions developed during the first year of anti-TNF treatment, while they developed in two patients during the second year. Two patients had to stop anti-TNF therapy due to the extent of skin lesions. All patients responded well to the local corticosteroid therapy. CONCLUSIONS: Our series strongly supports a link between TNF inhibition and the development of GA in some patients. When dealing with patients on these agents physicians should be aware of possible adverse events and the potential development of such complications.