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ID PMID Title PublicationDate abstract
19035505 Disease activity-guided rituximab therapy in rheumatoid arthritis: the effects of re-treat 2008 Dec OBJECTIVE: To explore the efficacy of re-treatment with rituximab in patients with rheumatoid arthritis (RA) who were initial nonresponders to treatment, and to evaluate the effects of rituximab in RA when re-treatment is given in a standardized way based on the Disease Activity Score in 28 joints (DAS28), according to the international consensus statement. METHODS: Patients with RA who had a DAS28 of > or =3.2 received up to 3 courses of rituximab at intervals of at least 6 months, regardless of whether the patient had responded to the first course of treatment with rituximab. RESULTS: Of the 30 patients with RA who were included in the study, 26 could be evaluated for the efficacy of treatment after 6 months. Eighteen patients qualified for re-treatment at 6 months, 6 patients were re-treated at a later time point because of a disease relapse, and 2 other patients were not re-treated because they had low disease activity. Seven of the 24 patients who qualified for re-treatment had not exhibited clinical improvement after the first treatment course. These patients typically did not respond to subsequent courses of rituximab. Of interest, in the 17 patients who had exhibited a clinical response to the first course of rituximab, the second and third treatment courses resulted in European League Against Rheumatism responses similar to those observed after the first course, and no major relapses occurred before re-treatment. CONCLUSION: Rituximab re-treatment is not effective in patients who do not exhibit clinical improvement after the first treatment course, which is consistent with the notion that such patients represent a different pathogenetic subset of RA. Patients who initially responded to rituximab treatment experienced sustained benefit from DAS28-based systematic re-treatment according to the international consensus statement.
18501101 Incidence of lymphoma in patients with rheumatoid arthritis: a systematic review of the li 2008 Apr To our knowledge, this review is the most broad and only systematic survey to date of the rheumatology, oncology, and epidemiology literature to determine the prevalence of lymphoma in patients with rheumatoid arthritis (RA). This survey is analyzed to determine whether the association between RA and increased lymphoma risk is a result of the risks conferred by medications used to treat RA or a result of the disease itself. PubMed was searched for articles from 1964 to May 2007 using the Medical Subject Heading terms "arthritis, rheumatoid, and lymphoma." Twenty-six studies met inclusion and exclusion criteria and are included for review. Most studies confirmed an approximate 2-fold increase in lymphoma incidence in patients with RA. Contrary to a widely held belief about medication toxicity in RA, most studies did not reveal a statistically significant increased risk of lymphoma with methotrexate or azathioprine. An increased lymphoma incidence with tumor necrosis factor-alpha inhibitors was suggested; however, follow-up in the studies considered was too short to definitively determine increased risk. Most studies differed in which medications they evaluated in determining their impact on lymphoma risk, making studies difficult to compare. Confounding by disease severity (patients with the most severe disease are treated with the strongest medications) in most studies makes the association between lymphoma risk and medications and/or disease severity difficult to assess. Recent work suggests that it is the disease itself, not its treatment, that is associated with increased risk of lymphoma in patients with RA.
18369527 Visualization and localization of rheumatoid knee synovitis with FDG-PET/CT images. 2008 Dec We annually evaluated (18)F-fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG-PET/CT) scans for three consecutive years in a patient with rheumatoid arthritis. The inflammatory activity of the rheumatoid synovium was visualized in coronal and transverse sections by FDG-PET/CT. The extent and area of the synovial inflammation was relatively well delineated, and this technique was more informative in detecting inflammation than were conventional X-rays.
16715225 [Quantitative imaging in rheumatoid arthritis: from scoring to measurement]. 2006 May The need of clinical sciences to measure therapy effects on chronic illness led to development, evaluation, and publication of several radiological methods to monitor disease progression of rheumatic diseases. This review article explains the basics and background of scoring and measurement. The radiologist thus learns to report more compactly and to communicate the results more specifically.
18026071 Early clinical results of open and arthroscopic synovectomy in knee inflammation. 2007 Sep BACKGROUND: The authors compared early results of open and arthroscopic knee joint synovectomy in patients with nonspecific exudative synovitis and rheumatoid arthritis. MATERIAL AND METHODS: The study comprised two groups of patients matched for age, preoperative range of motion in the involved knee and etiology of synovitis. Group I included patients after open synovectomy and group II consisted of subjects following an arthroscopic procedure. Blood loss, analgesic intake, duration of hospitalization, range of flexion and extension in the involved knee at discharge as well as 3 and 6 months following surgery were compared, together with respective recurrence rates. RESULTS: A statistically significant decrease in blood loss and a shorter duration of hospitalization were found in group II compared to group I; no differences were observed in postoperative analgesic use. Mean flexion range was significantly greater before surgery than in the 3 analyzed time intervals in both study groups except for knee flexion in group II compared before and 6 months following the intervention. However, mean flexion range in the operated joint at discharge and 3 months postoperatively was significantly greater in group II as compared with group I. A comparison of the knee extension range between the groups revealed significantly higher values in group II at discharge, but no statistically significant differences were found in the subsequent follow-up assessments. However, flexion contractures developed 6 months after surgery in 5 patients from group I and in 1 patient from group II. No recurrence of effusion was observed in either group. CONCLUSIONS: According to the authors, arthroscopic synovectomy reduces blood loss following surgery, shortens duration of hospitalization and permits faster recovery.
18412310 Palindromic rheumatism is a common disease: comparison of new-onset palindromic rheumatism 2008 Jun OBJECTIVE: To determine the prevalence of palindromic rheumatism (PR) compared to new-onset rheumatoid arthritis (RA). METHODS: We reviewed 145 patients that had been newly diagnosed by a rheumatologist with either RA or PR between May 2004 and May 2006. RESULTS: Of these 145 patients, 51 were diagnosed with PR and 94 with RA. There was a similar female predominance with both conditions. The average age at diagnosis of PR was 49 years as compared to 56 years for RA. CONCLUSION: Palindromic rheumatism occurs more frequently than previously recognized.
17009244 IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheum 2006 Oct OBJECTIVE: The IKK complex regulates NF-kappaB activation, an important pathway implicated in the rheumatoid arthritis (RA) disease process. This study was undertaken to assess the efficacy of N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methylnicotinamide (ML120B), a potent and selective small molecule inhibitor of IKKbeta. METHODS: Polyarthritis was induced in rats by injection of Freund's complete adjuvant into the hind footpad. ML120B was administered orally twice daily, either prophylactically or therapeutically. Paw volumes and body weights were measured every 2-3 days throughout the study. We assessed bone erosions by several methods: histologic evaluation, quantitative micro-computed tomography (micro-CT) imaging analysis, and measurement of type I collagen fragments in the serum. Quantitative polymerase chain reaction was used to evaluate expression of messenger RNA for genes related to inflammation and to bone and cartilage integrity. RESULTS: Oral administration of ML120B inhibited paw swelling in a dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. We were able to directly demonstrate that NF-kappaB activity in arthritic joints was reduced after ML120B administration. Also, we observed that down-regulation of the NF-kappaB pathway via IKKbeta inhibition dampened the chronic inflammatory process associated with rat adjuvant-induced arthritis. CONCLUSION: The results of the present study suggest that IKKbeta inhibition is an effective therapeutic approach to treat both the inflammation and the bone/cartilage destruction observed in RA. Methods for the determination of serum markers for bone and cartilage destruction, as well as micro-CT analysis, may aid in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition therapy in humans.
17062382 Spontaneous rupture of the spleen in secondary amyloidosis: a patient with rheumatoid arth 2006 Sep A 63-year-old man who had had a history of rheumatoid arthritis presented with shock and hemoperitoneum, without a history of trauma. An emergency laparatomy revealed hemoperitoneum and splenic rupture with massive bleeding. Splenectomy was performed. Histopathological examination of the spleen revealed amyloid deposition in the wall of the vessels. Rectal biopsy revealed amyloid deposition in mucosa that indicating amyloidosis was systemic. Histochemical studies showed that amyloid was secondary or AA.
18850321 Coexistence of the monostatic Paget's disease, sensorimotor neuropathy and elderly onset r 2009 Mar Paget's disease is a chronic focal disease of the skeleton that affects up to 2-3% of the population over the age of 60. Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder, pelvic girdle and the neck. There are two incompletely overlapping subsets of RA that have been recognized: one exhibits the classical RA clinical picture, while the other has a PMR-like onset in later ages of life. We reported a rare case of monostatic Paget's disease, sensorimotor neuropathy and elderly onset rheumatoid arthritis in an elderly women.
17240111 Cryptococcal meningitis in a patient treated with infliximab. 2007 Apr Infliximab, a tumor necrosis factor-alpha inhibitor, is increasingly used for the therapy of different inflammatory conditions. We report the first case of cryptococcal meningitis in a patient treated with infliximab and other immunosuppressive agents, and review a further 5 reported cryptococcal infections. All of them involved fungal pneumonia. Outcome was favorable in all cases.
18261308 [Effects of RNAi on cyclooxygenase-2 expression and biologic activity of human rheumatoid 2007 Nov 6 OBJECTIVE: To screen highly efficient small interfering RNA (siRNA) targeting human cyclooxygenase-2 (hCOX-2) mRNA on human rheumatoid arthritis synovial fibroblasts (RASF) and to further study the impact there on prostaglandin E2 (PGE2) and cytokines, such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), timorous necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF). METHODS: 4 lines of COX-2 mRNA siRNA (1(#) - 4(#) siRNA) were designed and transfected into the fibroblasts from the synovial membrane of a patient with rheumatoid arthritis (RASF). Phorbol ester was added 4 hours later. A scrambled line (NC) group and a blank control (CTL) group were used. RT-PCR and Western blot ting were used to detect the mRNA and protein expression of COX-2 36 and 48 hours after transfection. The levels of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF were measured by ELISA. RESULTS: RT-PCR showed that the absorbance ratios of the positively interfering groups, NC, and 1(#) - 3(#) siRNA groups, to CTL group were 0.72, 0.3, 0.25, 0.4, and 0.04 respectively. The ratios of the positively interfering groups to CTL group were 1.04, 0.52, 0.39, 0.9, and 36 h after transfection and 1.05, 0.52, 0.51, 0.9, and 0.15 respectively 48 h after transfection. The levels of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF in the culture supernatant were lower in the 4(#) siRNA group than in other groups 24, 36, and 48 h after transfection. The death rates of RASF of all trial groups were within the range of 9% - 11% and there were not statistically significant differences between the CTL group and the siRNA groups or between the 4(#) siRNA and other siRNA groups. CONCLUSION: 4(#) siRNA effectively inhibits the expression of COX-2 mRNA and protein the level of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF in the clear supernatant of the 4(#) group is lowest.
18832606 Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid 2009 Jan TNF-alpha plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sex- and age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-alpha-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-alpha, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on endothelial cells challenged with TNF-alpha. Our results suggest that enhanced levels of CgA identify patients with extra-articular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA.
17075836 RhoA-mediated, tumor necrosis factor alpha-induced activation of NF-kappaB in rheumatoid s 2006 Nov OBJECTIVE: Increasing evidence indicates that RhoA may play a central role in the inflammatory response. This study was conducted to examine the role of RhoA in mediating the activation of NF-kappaB in tumor necrosis factor alpha (TNFalpha)-stimulated rheumatoid synoviocytes, and to evaluate the modulatory effects of statins on the TNFalpha-induced activation of RhoA and NF-kappaB and the secretion of proinflammatory cytokines by rheumatoid synoviocytes. METHODS: Rheumatoid synoviocytes obtained from patients with active rheumatoid arthritis were stimulated with TNFalpha and incubated with simvastatin (SMV) (1 muM). RhoA activity was assessed by a pull-down assay. NF-kappaB DNA binding activity and nuclear translocation of NF-kappaB were measured by a sensitive multiwell colorimetric assay and confocal fluorescence microscopy, respectively. RESULTS: TNFalpha stimulation elicited a robust increase in RhoA activity in a dose-dependent manner, and SMV mitigated this increase. TNFalpha also hastened NF-kappaB nuclear translocation of subunit p65 and increased DNA binding activity, luciferase reporter gene expression, degradation of IkappaB, and secretion of interleukin-1beta (IL-1beta) and IL-6. SMV prevented the increase in NF-kappaB activation and rise in IL-1beta and IL-6 levels induced by TNFalpha, whereas mevalonate and geranylgeranyl pyrophosphate reversed the inhibitory effects of SMV on activation of NF-kappaB and RhoA. Furthermore, cotransfection with a dominant-negative mutant of RhoA demonstrated that the TNFalpha-induced signaling pathway involved sequential activation of RhoA, leading to NF-kappaB activation and, ultimately, to secretion of cytokines. CONCLUSION: This study identifies RhoA as the key regulator of TNFalpha-induced NF-kappaB activation, which ultimately results in the secretion of proinflammatory cytokines in rheumatoid synoviocytes. The findings provide a new rationale for the antiinflammatory effects of statins in inflammatory arthritis.
18682414 Clinical aspects of vitamin D in the management of rheumatoid arthritis. 2008 Nov There is an increasing interest in the role of vitamin D as a potential treatment for a number of disparate diseases. In addition to its role in calcium homeostasis, vitamin D has a plethora of effects including immunomodulation, pleiotropic effects, modulating propensity to infection and blood pressure regulation. Detection and treatment of vitamin D deficiency in selected patients with RA is relevant as deficiency is common. Vitamin D therapy may modify the increased risk of falls and fracture in this group, and possibly exert additional immunomodulatory effects on disease onset and activity although data are largely epidemiological. Currently, there is no consensus view on vitamin D replacement regimens, nor an agreed optimal level of serum 25-hydroxyvitamin D [25(OH)D] for health. Indeed levels may vary for different organ systems and the concept of 'tissue specific vitamin D deficiency' needs to be considered. Therefore, there is clinical uncertainty regarding both when and how to correct vitamin D deficiency. Older patients, particularly post-menopausal women, and others at high risk of vitamin D deficiency should be preferentially targeted since they are likely to benefit most from supplementation. Clinicians should be aware of the technical difficulties associated with measuring and interpreting 25(OH)D levels. The administration of high-dose vitamin D as an oral weekly bolus is safe and can rapidly correct vitamin D deficiency followed by regular lower doses to maintain adequate levels.
17662291 Fatigue as experienced by patients with rheumatoid arthritis (RA): a qualitative study. 2008 Jul OBJECTIVE: Interest in fatigue research has grown since the finding that fatigue is, besides pain, the symptom most frequently reported by patients with rheumatoid arthritis (RA). The aim of this study was to explore the experience of fatigue from the patients' perspective. METHODS: Twenty-nine patients with RA filled-out written questionnaires on fatigue severity, disability, quality of life and sleep disturbance, and disease activity was calculated using the Disease Activity Score (DAS28). All patients were individually interviewed and asked about fatigue. Qualitative analyses were completed using software program "The Observer". Basic codes, a code plan and coding rules were developed by two researchers through a consensus-based review process. Frequencies of the central codes were calculated by the program SPSS. RESULTS: RA fatigue is verbalised as a physical everyday experience with a variety in duration and intensity. Its sudden onset and exhausting nature is experienced as frustrating and causing anger. Patients mentioned having RA as the main cause of their fatigue. The consequences of fatigue are overwhelming and influence patients' everyday tasks, attitudes and leisure time. Patients described how they have to find their own management strategies by trial and error and described pacing and rest, relaxation and planning activities as the most appropriate interventions. Downward comparison and acceptance as part of the disease are also reported as successful coping strategies for fatigue. Most patients did not discuss fatigue with clinicians explicitly, accepting that they were told that fatigue is part of the disease and believing that they have to manage it alone. CONCLUSION: The results show that RA fatigue is experienced as being different from "normal" fatigue. Patients do not expect much support from health care professionals, assuming that they have to manage fatigue alone as it is part of the disease. These results will help professionals caring for RA patients to communicate about fatigue, to explore the nature of fatigue individually and to develop tailored interventions.
18025440 Systematic review: comparative effectiveness and harms of disease-modifying medications fo 2008 Jan 15 BACKGROUND: The comparative effectiveness of rheumatoid arthritis therapies is uncertain. PURPOSE: To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis. DATA SOURCES: Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007. STUDY SELECTION: Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies. DATA EXTRACTION: Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol. DATA SYNTHESIS: Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti-tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti-tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs. LIMITATION: Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions. CONCLUSION: Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis.
18975365 Vitamin E in the primary prevention of rheumatoid arthritis: the Women's Health Study. 2008 Nov 15 OBJECTIVE: Vitamin E supplements may reduce the risk of developing rheumatoid arthritis (RA) through antioxidant effects. Although previous observational studies have investigated this question, no randomized trial data are available. METHODS: The Women's Health Study is a randomized, double-blind, placebo-controlled trial designed to evaluate the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals age > or = 45 years throughout the US, conducted between 1992 and 2004. After excluding women with self-reported RA at baseline, 39,144 women were included in the present study. The primary end point, definite RA, was confirmed using a connective tissue disease screening questionnaire, followed by medical record review for American College of Rheumatology criteria. RESULTS: During an average followup of 10 years, 106 cases of definite RA occurred, 50 in the vitamin E group and 56 in the placebo group. Sixty-four (60%) RA cases were rheumatoid factor positive and 42 (40%) were rheumatoid factor negative. There was no significant association between vitamin E and risk of definite RA (relative risk [RR] 0.89, 95% confidence interval [95% CI] 0.61-1.31). There were also no significant risk reductions for either seropositive RA (RR 0.64, 95% CI 0.39-1.06) or seronegative RA (RR 1.47, 95% CI 0.79-2.72). CONCLUSION: Six hundred IU of vitamin E supplements taken every other day is not associated with a significant reduction in the risk of developing RA among women in a randomized, double-blind, placebo-controlled trial.
17581335 Axillary lymph node visualization on F-18 FDG PET body scans in patients with rheumatoid a 2007 Jul PURPOSE: We report benign axillary tracer uptake on F-18 FDG PET scans in patients with rheumatoid arthritis. PATIENTS AND METHODS: Axillary tracer uptake was observed in 9 patients who were undergoing PET for staging or restaging of malignancy. The uptake was not in a pattern that would be expected for the patients' known malignancies. Additional clinical information was obtained and quantitation of tracer uptake in the upper extremities and axillae was performed. RESULTS: All 9 patients were found to have rheumatoid arthritis. Increased axillary tracer uptake was bilateral in 7 patients and unilateral in 2 patients. In 8 of the patients the wrists were included in the field of view and showed elevated FDG uptake. On follow-up there was no evidence of malignancy in any of the axillary foci. CONCLUSION: Increased axillary tracer uptake on F-18 FDG PET scans can be seen in conjunction with increased uptake in the wrists in patients with rheumatoid arthritis, and is not necessarily an indication of malignancy.
18819772 [Rheumatoid arthritis and pregnancy]. 2008 Nov During pregnancy, oestrogen and progesterone levels are increased. Consequently the initial predominant immune cellular response (Th1 type) is decreased, whereas humoral response (Th2 type) is increased. Due to this switch, a lot of Th2 anti-inflammatory cytokines IL-4 and IL-10 are synthesized. During the last months of pregnancy Treg lymphocytes level is elevated leading to overexpression of IL-4 and IL-10. Due to these mechanisms, reduce disease activity of rheumatoid arthritis (RA) occurred. Impaired fertility has not been demonstrated in women with RA. However, some studies suggest that polyarthritis could induced a reduced weight at birth and more frequent pregnancy and delivery complications. Methotrexate and biotherapies have demonstrated no effect on fertility; however these drugs must be stopped before conception for a period equal to seven fold of the half live of the molecule. No teratogenic effect are known for sulfazalasine and hydroxychloroquine; these drugs could be used during pregnancy. It is also the same for ciclosporine, which used is quite unfrequent in RA. Methotrexate is teratogenic in animal models and is forbidden during pregnancy. For leflunomide which is metabolised in A771726, highly teratogenic, a washout period of 3,5 months is necessary. All commercially available TNFalpha inhibitors are classified by the food and Drug Administration as pregnancy risk category B: no adverse pregnancy adverse effects have been observed in animal studies, but there have been insufficient controlled human studies. The published experiences with TNFalpha inhibition in pregnancy is limited to some case reports and ongoing registry. More recently some cases of Vater syndromes (polymalformations) were possibly related to TNFalpha blocking agents. Such treatment must be avoided during pregnancy. Only few case reports are published concerning rituximab use during pregnancy. No data have been found for abatacept.
17476613 Insulin resistance in patients with rheumatoid arthritis: effect of anti-TNFalpha therapy. 2007 Mar OBJECTIVES: We undertook this study to test the hypotheses that patients with active rheumatoid arthritis (RA) are insulin resistant and that anti-tumour necrosis factor-alpha (TNFalpha) therapy improves not only the clinical state of these patients but also their glucose metabolism. METHODS: Nine RA patients with active disease and nine healthy subjects, matched for sex, age, and body mass index (BMI), underwent a hyperinsulinaemic euglycaemic clamp. The RA patients received anti-TNFalpha therapy with Humira(adalimumab) and had the insulin clamp re-evaluated after 8 weeks of treatment. RESULTS: Patients with RA had marked insulin resistance (glucose infusion rate (GIR) area under the curve (AUC) was 499+/-55 mg/kg in the RA group compared to 710+/-77 mg/kg in the control group; p<0.05). However, insulin sensitivity did not differ before and after 8 weeks of adalimumab therapy. The RA patients demonstrated a reduction in C-reactive protein (CRP) and interleukin-6 (IL-6) levels after the therapy as compared to pretreatment values, but there was no concomitant effect on plasma levels of TNFalpha. CONCLUSION: RA patients with active disease showed marked insulin resistance that was not influenced by anti-TNFalpha therapy despite a reduction in systemic inflammation during the treatment.