Rheumatoid Arthritis: Drosos AA

Voulgari PV, Drosos AA. · University of Ioannina Medical School, Rheumatology Clinic, Department of Internal Medicine, 45110 Ioannina, Greece. · Expert Opin Biol Ther. · Pubmed #17223742 No free full text.

Abstract: In the last few years significant advances have been made in our understanding of the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro-inflammatory cytokines, such as TNF-alpha, play a pivotal role in its pathogenesis. Anti-TNF-alpha biological agents are considered a major advance in the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-alpha, thereby neutralising its activity. It had significant efficacy in well-designed, placebo-controlled trials in patients suffering from rheumatoid arthritis, both as monotherapy and in combination with various disease-modifying antirheumatic drugs, including methotrexate. Adalimumab was generally well tolerated during both concomitant therapy with methotrexate or standard antirheumatic therapy and monotherapy. In addition, the radiographic progression of structural joint damage was significantly inhibited by adalimumab and improved quality of life. This review summarises the recent available data.

Alamanos Y, Voulgari PV, Drosos AA. · Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Ioannina, Greece. · Semin Arthritis Rheum. · Pubmed #17045630 No free full text.

Abstract: OBJECTIVES: To conduct a systematic review of incidence and prevalence studies of rheumatoid arthritis (RA), based on the 1987 revised American College of Rheumatology (ACR) criteria, to compare their methodologies and summarize their results, and to investigate the possible geographic variations and changes over time in the frequency of the disease. METHODS: We conducted a Medline search between January 1988 and December 2005. Studies reporting the incidence and prevalence of RA in adult populations (16 to 20 years and over), based on 1987 ACR criteria, were eligible for inclusion. From each study included, we extracted the country, year of publication, type of study (retrospective, prospective, or cross-sectional), and incidence or prevalence rates. The study areas were grouped into (a) North American countries; (b) north European countries; (c) south European countries; and (d) developing countries. We examined the geographical differences of prevalence and incidence rates using the Mann-Whitney and the Kruskall-Wallis tests. RESULTS: A total of 28 studies were identified meeting the inclusion criteria. Nine were incidence studies, 17 were prevalence studies, and 2 estimated both prevalence and incidence rates. Incidence studies were not available from developing countries. There is a significant difference of prevalence estimates between northern European and American countries and developing countries. South European countries have lower median incidence rates than North American and north European countries. As concerning the time trends of RA occurrence, only 3 incidence studies provided secular data from the same study area, based on ACR criteria, using the same methods of case ascertainment. Two of these studies indicate a decreasing incidence of RA in Finland and United States of America. CONCLUSIONS: The occurrence of RA varies among countries and areas of the world. A decreasing trend has been observed in countries characterized by high rates of RA incidence and prevalence. However, the relatively small number of studies for most areas of the world and the lack of incidence studies for the developing countries limits the understanding of worldwide RA epidemiology.

Alamanos Y, Tsifetaki N, Voulgari PV, Venetsanopoulou AI, Siozos C, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece. · Rheumatology (Oxford). · Pubmed #16332955 links to  free full text

Abstract: OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sjögren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.

Alamanos Y, Drosos AA. · Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Ioannina, Greece. · Autoimmun Rev. · Pubmed #15823498 No free full text.

Abstract: Several incidence and prevalence studies of rheumatoid arthritis (RA) have been reported during the last decades, suggesting a considerable variation of the disease occurrence among different populations. The majority of studies carried out in Northern European and North American areas estimate a prevalence of 0.5-1%, and a mean annual incidence of 0.02-0.05%. The occurrence of the disease seems to be lower in other parts of the world. Some studies from North American, North European, and Japanese populations suggest a decline in both the prevalence and incidence of the disease after the 1960s. RA is related to an increased mortality, and the expected survival of RA patients is likely to decrease 3-10 years. There is epidemiological evidence that genetic factors are related to an increased risk of RA. However, RA is considered to be a multifactorial disease, resulting from the interaction of both genetic and environmental factors, which contribute to its occurrence and expression. The main risk factors for the disease include genetic susceptibility, sex and age, smoking, infectious agents, hormonal, dietary, socioeconomic, and ethnic factors. Most of these factors are likely to be associated with both disease occurrence and severity.

Kozanidou VI, Theocharis AD, Georgiadis A, Voulgari PV, Drosos AA, Karamanos NK. · Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece. · Curr Drug Targets Immune Endocr Metabol Disord. · Pubmed #15777203 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic and destructive arthropathy with systemic features, the etiopathogenesis of which remains unclear. It is characterized by relapsing and remitting inflammation and hyperplasia of synovial cells. Proinflammatory cytokines, such as interleukin-2 (IL-2), play an important role in maintaining cartilage damage and severe destruction of the joints due to an uncontrolled activation of cellular immunity. An imbalance between proinflammatory and anti-inflammatory mediators is likely to contribute to the chronicity of the disease. Therefore, insight into the activation state of T-cells in different stages of the disease may be important to understand pathogenetic mechanisms underlying RA and could be a lead for the design of future therapeutic strategies. Because of the central role of the IL-2/IL-2 receptor (IL-2R) system in mediation of the immune system, monitoring and manipulation of this system has important diagnostic and therapeutic implications. New approaches in RA therapy with anticytokine agents, which block cytokines and their receptors, are now used as antirheumatic drugs in clinical practice.

Voulgari PV, Papazisi D, Bai M, Zagorianakou P, Assimakopoulos D, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece. · Rheumatol Int. · Pubmed #15761726 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, which causes joint damage and bone destruction. Extra-articular manifestations are numerous, involving multiple organ systems. Rheumatoid nodules are common extra-articular findings occurring in 20% RA patients. They develop most commonly in pressure areas (elbows and finger joints) and may occasionally affect internal organs including pleura, lungs, meninges, larynx, and others. Furthermore, RA affects the ear, nose, and throat, causing various otorhinolaryngological symptoms. In this report we describe two patients with RA and laryngeal involvement, mostly rheumatoid nodule formation, with a review of the literature.

Nikas SN, Drosos AA. · University of Ioannina Medical School, Department of Internal Medicine, Division of Rheumatology, Ioannina 45110, Greece. · Curr Opin Investig Drugs. · Pubmed #15573872 No free full text.

Abstract: SCIO-469 is a small-molecule p38 mitogen-activated protein (MAP) kinase inhibitor under development by Scios Inc as a potential oral therapy for inflammatory disorders. By July 2004, SCIO-469 was in phase lib clinical trials for rheumatoid arthritis.

Drosos AA. · Rheumatology Clinic, Department of Internal Medical School, University of Ioannina, 45110, Ioannina, Greece. · Autoimmun Rev. · Pubmed #15309773 No free full text.

This publication has no abstract.

Drosos AA. · Section of Rheumatology, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Drugs. · Pubmed #11929337 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterised by chronic synovitis, which leads to cartilage damage and joint destruction. It is generally a progressive disease with radiographic evidence of joint damage, functional status decline and premature mortality. Proinflammatory cytokines, such as interleukin 1 and tumour necrosis factor alpha, play an important role in maintaining the chronicity of RA and mediating tissue damage. New approaches in the therapy of RA with anticytokine biological agents, which neutralise or block cytokines or their receptors, are now the first generation antirheumatic drugs in clinical practice. A better understanding of the signal transduction systems and gene regulation by transcription factors involved in cytokine production has opened the way for the discovery of novel therapeutic compounds useful in treating patients with RA. Overactivation of selective kinases or aberrant function of downstream transcription factors could help convert a normal immune response to a chronic disease state. This provides a unique opportunity for novel therapeutic interventions, since specific signal transduction or transcription factor targets might interrupt the perpetuation mechanisms in RA. The availability of potent and selective p38 mitogen activated protein kinase inhibitors provide a means in further dissecting the pathways implicated in cytokine production, which in turn maintain the chronicity of RA. Many studies conclude that these compounds are very useful in the treatment of chronic synovitis and therefore are very promising for RA treatment.

Kiortsis DN, Mavridis AK, Filippatos TD, Vasakos S, Nikas SN, Drosos AA. · Department of Internal Medicine, and the Rheumatology Clinic, Medical School, University of Ioannina, Ioannina, Greece. · J Rheumatol. · Pubmed #16541480 No free full text.

Abstract: OBJECTIVE: To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. RESULTS: Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. CONCLUSION: The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.

Zikou AK, Argyropoulou MI, Voulgari PV, Xydis VG, Nikas SN, Efremidis SC, Drosos AA. · Department of Radiology and the Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Greece. · J Rheumatol. · Pubmed #16465650 No free full text.

Abstract: OBJECTIVE: To investigate the clinical response and to evaluate by magnetic resonance imaging (MRI) the inflammatory tissue changes in patients with refractory rheumatoid arthritis (RA) treated with adalimumab. METHODS: Thirteen patients with refractory RA who were treated with adalimumab (40 mg every 2 weeks subcutaneously) were examined with MRI of the dominant affected wrist and hand before treatment and one year after therapy. The volume of the enhanced inflammatory tissue (VEIT) was evaluated in fat-suppressed contrast-enhanced T1-weighted MRI images using the Analyse 4.0 software. Disease activity was evaluated using the Disease Activity Score 28-joint (DAS-28). Clinical improvement was evaluated according to the American College of Rheumatology 20% response criteria (ACR20%). RESULTS: We studied 12 women and one man, with mean age 52.0 +/- 10.9 years and mean disease duration 13.0 +/- 8.5 years. Eight patients had positive IgM rheumatoid factor. One year after treatment, 11 (84.6%) patients showed a decrease of the VEIT. Moreover the values of C-reactive protein (CRP; 4.3 +/- 6.6 mg/l), the erythrocyte sedimentation rate (ESR; 26.3 +/- 19.5 mm/h), the DAS-28 (3.5 +/- 1.1), and the VEIT (21.6 +/- 10.7 cm3) after treatment were significantly lower compared to the corresponding values before treatment (CRP 41.6 +/- 39.2), (ESR 54.3 +/- 28.6) (DAS-28 5.8 +/- 0.8), and (VEIT 36.9 +/- 16.8) (p < 0.01). All but 3 (76.9%) patients with RA achieved the ACR20% response, while 7 (53.8%) and 5 (38.5%) patients achieved ACR50% and ACR70% response, respectively. A positive correlation between VEIT, swollen joint count, and ESR was found before treatment (r = 0.59, r = 0.64, respectively; p < 0.05). CONCLUSION: In patients with refractory RA, treatment with adalimumab resulted in improvement of clinical, laboratory, and MRI findings. MRI assessment of the VEIT may represent an additional tool for investigation of joint disease activity and responsiveness to treatment.

Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV, Psilas K, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Ann Rheum Dis. · Pubmed #14644860 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). RESULTS: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated.

Temekonidis TI, Georgiadis AN, Alamanos Y, Bougias DV, Voulgari PV, Drosos AA. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Ann Rheum Dis. · Pubmed #12176808 links to  free full text

Abstract: OBJECTIVE: To investigate whether infliximab can be used in combination with cyclosporin A (CsA) in patients with refractory rheumatoid arthritis (RA) who cannot tolerate methotrexate (MTX). MATERIALS AND METHODS: Eighteen patients with refractory RA receiving low dose CsA (2 mg/kg/day) and prednisone (5 mg/day) were treated with intravenous infliximab. The patients were given infliximab (3 mg/kg weight) at 0, two, six, and every eight weeks thereafter for a total period of 12 months. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% response criteria. RESULTS: Eighty per cent of patients receiving the combination treatment with CsA and infliximab achieved the 20% ACR criteria for response to treatment, whereas 39% satisfied the 50% response criteria. In addition, a 76% reduction in swollen and tender joint count was found. Finally, a reduction in C reactive protein and erythrocyte sedimentation rate was maintained throughout the study. In general, treatment was well tolerated, with minimal adverse drug reactions. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. CONCLUSION: Multiple infusions of infliximab and low doses of CsA improve patients with refractory RA. It seems that CsA may be an alternative disease modifying drug to be used in combination with infliximab in patients with refractory RA who cannot tolerate MTX.

Drosos AA, Voulgari PV, Katsaraki A, Zikou AK. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Rheumatol Int. · Pubmed #10776690 No free full text.

Abstract: The aim of this study was to evaluate whether cyclosporin A (CsA) influences the radiological disease progression in early rheumatoid arthritis (RA) patients in comparison with other disease-modifying drugs (DMARDs). A total of 103 early RA patients, without prior use of DMARDs, were randomized to receive CsA (3 mg/kg per day) or methotrexate (MTX) (0.15 mg/kg per week). In addition, all patients received prednisone (7.5 mg/day). After 42 months of treatment, pairs of hand and wrist radiographs of 41 patients treated with CsA and 42 treated with MTX were evaluated blindly and separately by two investigators, using reference radiographs for scoring. A scale scoring similar to Larsen's standard radiographs with minor modifications was used. The studied radiographs were obtained at the beginning and 42 months after therapy in both groups. Patients in both groups responded beneficially to the above treatment regimens. In the CsA group, 37 patients (71 %) remained radiographically stable and 4 worsened, while in the MTX group 39 patients (76%) remained stable and 3 deteriorated. No significant radiological worsening was found in the CsA-treated patients as compared to those treated with MTX. Early immuno-intervention in RA patients appears to be crucial for the future development of joint damage: CsA can delay radiological disease progression and may inhibit joint damage deterioration in early RA patients.

Voulgari PV, Efremidis SC, Drosos AA. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Clin Exp Rheumatol. · Pubmed #10464562 No free full text.

This publication has no abstract.

Drosos AA, Voulgari PV, Psychos DN, Tsifetaki N, Bai M. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Rheumatol Int. · Pubmed #10399792 No free full text.

Abstract: Out of 134, 12 sarcoidosis patients with symptoms of mucosal dryness as the first clinical manifestation were identified and compared with 30 consecutive unselected Sjögren's syndrome (SS) patients. Sicca manifestations were similar among the two groups, while parotid gland enlargement (PGE) was more frequently found in sarcoidosis patients (P < 0.05). Patients with sarcoidosis had mainly pulmonary (P < 0.001) and skin involvement (P < 0.05), while SS patients presented more frequently with Raynaud's phenomenon (P < 0.05). Autoantibody profile was more often found in SS patients compared to sarcoidosis (P < 0.0025). The histopathological findings of minor salivary gland biopsy (MSGB) revealed noncaseating granulomas (NCG) in 58% of patients with sarcoidosis, while in SS, MSGB showed focal sialadenitis in the majority of the patients. Transbronchial lung biopsy (TBLB), which was performed in 10 sarcoidosis patients, revealed the presence of NCG in all patients. In patients with sarcoidosis and sicca symptoms as the presenting syndrome, PGE is a useful clinical finding. Searching for pulmonary involvement is a determining factor to differentiate sarcoidosis from SS. The absence of autoantibodies is another useful tool for the diagnosis of sarcoidosis. Finally, MSGB is very helpful to discriminate between sarcoidosis and SS and when MSGB is not specific, then TBLB is valuable to confirm the diagnosis.

Voulgari PV, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · J Rheumatol. · Pubmed #18843757 No free full text.

This publication has no abstract.

Chatzikyriakidou A, Georgiou I, Voulgari PV, Georgiadis AN, Argyriou ES, Drosos AA. · Genetics Unit, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina, Greece. · Scand J Rheumatol. · Pubmed #18830906 No free full text.

Abstract: OBJECTIVES: Deregulation of glucocorticoid (GC) secretion could be associated with rheumatoid arthritis (RA). The GC receptor (GR) has two isoforms. In the present study, we explored the role of GR-alpha polymorphisms rs33388, rs33389, and Bcl I, and the GR-beta variant rs6198 in RA susceptibility. METHODS: One hundred and thirty-six RA patients and 148 ethnic matching controls were studied. Polymorphisms rs33388 and Bcl I were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and variants rs33389 and rs6198 by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) coupled with sequencing. Arlequin and SPSS softwares were used in the statistical analysis. RESULTS: The polymorphisms studied were in Hardy-Weinberg equilibrium in both groups. A marginally statistical significant difference was observed in the distribution of rs33388 genotypes between RA patients and controls (p = 0.053). When the A and T alleles were compared, the statistical significance was p = 0.025. Specific complex genotypes were also differentially distributed: the GR-alpha complex genotypes (a) [homozygote (homo) wild-type (wt) rs33388-homo wt rs33389] (11% RA vs. 21% controls; p = 0.023), (b) [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I] (0.7% RA vs. 4.7% controls; p = 0.042), and (c) the GR-beta complex genotype [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I-homo wt rs6198] (0.7% RA vs. 4.7% controls; p = 0.042). CONCLUSIONS: GR-alpha and GR-beta polymorphisms are potentially associated with RA susceptibility. However, additional studies in larger and other ethnic groups of patients are needed to confirm the results of the present study.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Voulgari PV, Alamanos Y, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Curr Clin Pharmacol. · Pubmed #18666381 No free full text.

Abstract: Infliximab, a chimeric monoclonal anti-tumor necrosis factor alpha antibody is approved for the treatment of patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) therapy. This report provides analyses by using infliximab in combination with various disease modifying anti-rheumatic drugs, infliximab "survival" over a period of three years, and its effectiveness on synovial tissue damage using magnetic resonance (MR) imaging. The study was started in 1999 as an open label study using infliximab in combination with cyclosporin A (CsA) in refractory RA patients who were unable to tolerate MTX. A total of 18 RA patients were investigated. After a year of treatment, 80% of patients achieved the 20% American College of Rheumatology Response criteria. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. In a subsequent study we investigated infliximab "survival" over a period of 3 years. A total of 84 RA patients were included in the study. After 3 years of therapy, 59% of patients still continued receiving infliximab. The factor that was associated with infliximab "survival" was the concomitant use of MTX. A total of 28 (33%) patients discontinued this study. More specifically, 16 (19%) presented adverse drug reactions, 9 (11%) had drug failure, and 3 (3%) were lost from follow-up. Finally, to evaluate by MR imaging the inflammatory tissue changes in refractory RA patients treated with infliximab, 16 patients were examined with MR imaging of the dominant affected wrist and hand before and one year after therapy. The volume of the enhancing inflammatory tissue (VEIT) was evaluated. A significant decrease of VEIT was observed in 88% of patients after therapy. We conclude that in refractory RA patients infliximab was proved to be efficacious and well tolerated in combination with CsA. The clinical response of infliximab was persistent over a 3-year period and was associated with the concomitant use of MTX. This clinical improvement was also associated with the reduction of inflammatory disease tissue damage.

Georgiadis AN, Voulgari PV, Argyropoulou MI, Alamanos Y, Elisaf M, Tselepis AD, Drosos AA. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Semin Arthritis Rheum. · Pubmed #18191989 No free full text.

Abstract: OBJECTIVE: To investigate subclinical atherosclerosis and the effect of treatment in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: Forty patients with early RA who met the revised American College of Rheumatology (ACR) criteria and disease duration of <1 year were included in the study. Smokers and patients with classical risk factors for atherosclerosis were excluded. The serum levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were determined in all patients before and after 1 year of therapy. Carotid artery intima-media thickness (IMT) and carotid plaque were measured before and after treatment. RA disease activity was measured using the 28 joint indices score (DAS-28) and clinical improvement was determined by the ACR response criteria. Forty-five age- and sex-matched nonsmoking volunteers were used as controls. All patients were treated with methotrexate and prednisone. RESULTS: RA patients had a baseline mild dyslipidemia characterized by a decrease in serum HDL-C levels and a high TC/HDL-C atherogenic ratio compared with controls. Both lipid parameters were significantly improved after treatment (P<0.01). Common carotid artery IMTs at baseline were higher in RA patients compared with controls (P<0.05). After 1 year of therapy there was a significant decrease in the IMTs (P<0.001). Thirty-five patients (88%) achieved the ACR 20%, while 30 (75%) reached the ACR 50% response criteria. A significant decrease of DAS-28 was observed after treatment (P<0.03). CONCLUSIONS: The atherogenic lipid profile and subclinical atherosclerosis are features of early RA, which improved after therapy. Early intervention and control of the disease activity may reduce the risk of atherosclerosis and cardiovascular events in patients with RA.

Sokka T, Häkkinen A, Kautiainen H, Maillefert JF, Toloza S, Mørk Hansen T, Calvo-Alen J, Oding R, Liveborn M, Huisman M, Alten R, Pohl C, Cutolo M, Immonen K, Woolf A, Murphy E, Sheehy C, Quirke E, Celik S, Yazici Y, Tlustochowicz W, Kapolka D, Skakic V, Rojkovich B, Müller R, Stropuviene S, Andersone D, Drosos AA, Lazovskis J, Pincus T, Anonymous00085. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Arthritis Rheum. · Pubmed #18163412 links to  free full text

Abstract: OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.

Metafratzi ZM, Georgiadis AN, Ioannidou CV, Alamanos Y, Vassiliou MP, Zikou AK, Raptis G, Drosos AA, Efremidis SC. · Department of Clinical Radiology and Imaging, Medical School of Patras, Greece. · Scand J Rheumatol. · Pubmed #17963162 No free full text.

Abstract: OBJECTIVES: To assess the pleuropulmonary changes in patients with early rheumatoid arthritis (RA), using high-resolution computed tomography (HRCT). METHODS: Forty-three non-smoking patients with early RA were included. The disease duration was<1 year, without previous treatment. Disease activity was assessed using the 28-joint indices score (DAS28). Hand and wrist X-rays were evaluated using Larsen's criteria. Pulmonary functional tests (PFTs) were performed in 32 patients. The patients and 18 non-smokers healthy individuals were assessed by plain chest X-ray (CXR) and HRCT of the lungs. RESULTS: HRCT revealed air trapping in 69% (25/36), bronchiectasis in 58% (25/43), bronchial wall thickening in 52% (22/43) and ground glass opacities (GGOs) in 35% (15/43) of the patients. Pleural thickening and effusion were observed in 11% (5/43). CXR was abnormal in one patient revealing a single pulmonary nodule. GGOs were the only HRCT sign observed exclusively in RA patients. All the other abnormalities were depicted in the control group at the same frequency as in the patients. However, the extent (as expressed by the HRCT score) of air trapping, bronchiectasis and bronchial wall thickening was significantly greater in the patients than in the control group (p<0.05). The PFTs were within normal values. DAS28, PFTs, and the Larsen score did not show any significant correlation with either each HRCT sign score separately or the total score. CONCLUSIONS: Lung abnormalities are frequently observed in patients with early RA on HRCT, even when CXR and PFTs are normal. Limited areas of GGOs were the abnormalities depicted exclusively in patients.

Voulgari PV, Markatseli TE, Exarchou SA, Zioga A, Drosos AA. · Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Ann Rheum Dis. · Pubmed #17728330 No free full text.

Abstract: 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.

Hyphantis TN, Tsifetaki N, Siafaka V, Voulgari PV, Pappa C, Bai M, Palieraki K, Venetsanopoulou A, Mavreas V, Drosos AA. · Department of Psychiatry, Medical School, University of Ioannina, Ioannina, Greece. · Semin Arthritis Rheum. · Pubmed #17512572 No free full text.

Abstract: OBJECTIVE: To access health-related quality of life (HRQOL) in systemic sclerosis (SSc) patients using the World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF), and to identify the association between clinical, psychopathological, and personality parameters and SSc patients' HRQOL. METHODS: Fifty-six patients with SSc were compared with 72 patients with rheumatoid arthritis (RA), 43 with systemic lupus erythematosus (SLE), 34 with Sjögren syndrome (SS), and 74 healthy controls. A wide range of clinical information was collected and the following self-report instruments were used: the WHOQOL-BREF, the General Health Questionnaire, the Symptom Distress Check List, the Hostility and Direction of Hostility Questionnaire, the Defense Style Questionnaire, and the Sense of Coherence scale. RESULTS: HRQOL perceived by SSc patients was significantly impaired compared with healthy controls. Initial examination of HRQOL across groups of rheumatology patients revealed similar HRQOL, but when age, pain, psychopathology, and coping strategies were taken into account, SSc patients had impaired physical health QOL in comparison with RA, SLE, and SS patients. Arthritis-related pain was closely associated with SSc patients' HRQOL. Elevated psychological distress symptoms as well as certain personality traits, such as maladaptive defenses and lower sense of coherence, were also associated with diminished HRQOL. CONCLUSIONS: Impaired psychological functioning is associated with diminished HRQOL in SSc, and consequently, treatment of depressive symptoms should be considered a priority. Moreover, assessment of HRQOL should only be used in conjunction with specific psychological distress measurements, to detect the influence of psychopathology on HRQOL.