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ID PMID Title PublicationDate abstract
16821266 Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid 2006 Jul OBJECTIVE: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. METHODS: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. RESULTS: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant. CONCLUSION: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.
16229322 [Peripheral mononuclear cells and cytokine circulating levels during adalimumab therapy in 2005 Sep The aim of the study was to evaluate the composition and functional integrity of the various components of immune response in patients with rheumatoid arthritis (RA). We evaluated in 14 patients with RA with stable methotrexate therapy 12.5 mg/weekly, the number of peripheral mononuclear (PMN) cells lymphocytes, monocytes and the circulating levels of TNFalpha, IL-6 and IL-10 before and during adalimumab therapy 40 mg every other week for 6 months. No difference in baseline versus 6 months values between two treated group for PMN cells. Data about cytokines show a reduction for TNFalpha, IL-6 circulating levels and an increase for IL-10 circulating levels. Our data reveal that adalimumab doesn't reduce lymphocyte population and subsets such as CD14 or CD56 cells that have an important role against infections.
16357457 Development of calciphylaxis after long-term steroid and methotroxate use in a patient wit 2005 Nov Calciphylaxis may be considered a small vessel vasculopathy which is generaly associated with end-stage renal disease and hyperparathyroidism. The precise pathogenesis of the disease is not known. It needs sensitizers and challengers to occur. Steroids and immunosuppressive drugs including methotrexate are among those challenger agents. Calciphylaxis in collagen vascular diseases is rare. Only one case in rheumatoid arthritis was recently reported. Here we describe a case of calciphylaxis associated with active rheumatoid arthritis. This patient had active disease despite treatment of steroids and methotrexate for a long time. She died shortly after the diagnosis of calciphylaxis due to sepsis.
15851525 B cells in rheumatoid arthritis: from hypothesis to the clinic. 2005 May Rituximab (MabThera/Rituxan) is a therapeutic monoclonal antibody against CD20, an antigen expressed by B cells but not B-cell progenitor or plasma cells. It is currently approved for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) and is well tolerated and efficacious. A small open-label study (conducted by Edwards and Cambridge) indicated that selective depletion of B cells using rituximab led to sustained benefits for patients with active rheumatoid arthritis. A 24-week, double-blind, randomized controlled trial was carried out to confirm these initial observations. In total, 161 patients with active rheumatoid arthritis were randomized to one of four treatment groups: rituximab monotherapy; rituximab plus methotrexate (R+MTX); rituximab plus cyclophosphamide (R+CTX); or methotrexate alone (MTX). Rituximab was administered as two 1000 mg infusions on days 1 and 15. An analysis at 24 weeks showed that the proportion of patients achieving an ACR20 response was significantly greater (P < or = 0.025 for all three comparisons) in all the rituximab groups compared with the MTX control group (rituximab alone, 65%; R+CTX, 76%; R+MTX, 73%; MTX alone, 38%). Both ACR50 (43 vs 13%; P = 0.005) and ACR70 (23 vs 5%; P = 0.048) responses were also significantly higher for the R+MTX group compared with the MTX group. The rituximab groups showed no significant safety differences compared with the MTX arm. The majority of adverse events were of mild to moderate intensity. Rituximab is a novel targeted therapy for the treatment of rheumatoid arthritis and it appears to be highly effective, safe and well tolerated.
16447240 Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus 2006 Feb OBJECTIVE: To compare the efficacy of doxycycline plus methotrexate (MTX) versus MTX alone in the treatment of early seropositive rheumatoid arthritis (RA), and to attempt to differentiate the antibacterial and antimetalloproteinase effects of doxycycline. METHODS: Sixty-six patients with seropositive RA of <1 year's duration who had not been previously treated with disease-modifying antirheumatic drugs were randomized to receive 100 mg of doxycycline twice daily with MTX (high-dose doxycycline group), 20 mg of doxycycline twice daily with MTX (low-dose doxycycline group), or placebo with MTX (placebo group), in a 2-year double-blind study. Treatment was started with an MTX dosage of 7.5 mg/week, which was titrated every 3 months until remission was reached (maximum dosage of 17.5 mg/week). The primary end point was an American College of Rheumatology 50% improvement (ACR50) response at 2 years. RESULTS: ACR50 responses were observed in 41.6% of patients in the high-dose doxycycline group, 38.9% of those in the low-dose doxycycline group, and 12.5% of patients in the placebo group. Results of chi-square analysis of the ACR50 response in the high-dose doxycycline group versus that in the placebo group were significantly different (P = 0.02). Trend analysis revealed that the ACR20 response and the ACR50 response were significantly different between groups (P = 0.04 and P = 0.03, respectively). MTX doses at 2 years were not different among groups. Four patients in the high-dose doxycycline group, 2 patients in the low-dose doxycycline group, and 2 patients in the placebo group were withdrawn because of toxic reactions. CONCLUSION: In patients with early seropositive RA, initial therapy with MTX plus doxycycline was superior (based on an ACR50 response) to treatment with MTX alone. The therapeutic responses to low-dose and high-dose doxycycline were similar, suggesting that the antimetalloproteinase effects were more important than the antibacterial effects. Further studies to evaluate the mechanism of action of tetracyclines in RA are indicated.
16583424 Effect of etanercept on fatigue in patients with recent or established rheumatoid arthriti 2006 Apr 15 OBJECTIVE: To assess the long-term impact of etanercept on fatigue in patients with recent-onset (mean duration 11 months) or established (mean duration 12 years) rheumatoid arthritis (RA). METHODS: Patients participating in either of 2 multicenter, randomized, double-blind clinical trials were included. In one trial, patients with recent-onset RA received either etanercept 25 mg twice weekly or methotrexate in a double-blind fashion for 12 months, then open label for 12 months. All patients then received open-label etanercept. In the second trial, patients with established RA received etanercept 25 mg or placebo twice weekly for 6 months in a double-blinded fashion, then open-label etanercept. Up to 46 months of followup data were included. Fatigue was measured regularly using the Health Assessment Questionnaire vitality domain. RESULTS: Patients with recent-onset RA who received etanercept had a significantly faster improvement in fatigue than those receiving methotrexate in the first 2 months. Subsequently, patients receiving etanercept and methotrexate had 23-29% and 17-24% reductions in fatigue scores, respectively. In the group with established RA, patients who received etanercept had significantly greater reductions in fatigue than those receiving placebo during the blinded period. Patients initially receiving etanercept sustained a mean fatigue reduction of 25-36% for the entire followup. Patients achieving clinically meaningful improvement in fatigue were more likely to meet the American College of Rheumatology improvement criteria. CONCLUSION: Etanercept therapy reduces fatigue in patients with recent-onset or established RA. Improvement in fatigue was sustained for up to 46 months, and correlated with other RA-relevant outcomes.
16540550 Low-cost, low-field dedicated extremity magnetic resonance imaging in early rheumatoid art 2006 Sep OBJECTIVE: To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS: 24 previously untreated patients with rheumatoid arthritis with joint symptoms for <1 year were evaluated at the time of diagnosis and after 6 and 12 months of methotrexate treatment with conventional clinical or biochemical examinations, x rays of both hands and wrists, and E-MRI of the dominant wrist and MCP joints. RESULTS: At baseline, all patients showed magnetic resonance imaging (MRI) synovitis, and MRI erosions were detected in 21 bones (10 patients). 6 (29%) of these, distributed among two patients, were seen on x ray. One x ray erosion was not detected by MRI. At 1 year, MRI and x ray detected 15 and 8 new erosions, respectively, and 19% of MRI erosions at baseline had progressed to x ray erosions. In bones with MRI erosions at baseline, the relative risk of having x ray erosions at the 1-year follow-up was 12.1, compared with bones without baseline MRI erosions (lesion-centred analysis). If bones with baseline x ray erosions were excluded, the relative risk was 5.2. In patients with baseline MRI bone erosion or oedema, the relative risk of having x ray erosions at 1 year was 4.0, compared with patients without these signs at baseline (patient-centred analysis). CONCLUSION: In this group of patients with early rheumatoid arthritis who were treated uniformly, baseline E-MRI erosions in MCP or wrist bones markedly increased the risk of x ray erosions at the 1-year follow-up. Low-cost, low-field dedicated extremity MRI is promising for assessment and prognostication of early rheumatoid arthritis.
16395746 Evolution of antinuclear antibodies and clinical patterns in patients with active rheumato 2006 Jan OBJECTIVE: To investigate the effect of longterm infliximab therapy on serum levels of fluorescent antinuclear and anti-double and single-stranded DNA antibodies (FANA, anti-dsDNA, anti-ssDNA) in patients with rheumatoid arthritis (RA), and their possible association with clinical evolution. METHODS: Sera from 58 RA patients, treated for one to 3 years with infliximab, were retrospectively analyzed. Matched control groups were RA patients treated with corticosteroids or methotrexate. FANA were tested using HEp-2 cells, and anti-dsDNA and anti-ssDNA IgG by ELISA. After 28 months of infliximab therapy, clinical status was evaluated in 43/58 patients with uninterrupted therapy and associations with autoantibody levels were investigated. Data were documented for patients who discontinued infliximab. RESULTS: Over the 3 year period, significant increases in FANA and anti-ssDNA IgG levels were observed in infliximab treated patients (p < 0.001 and p < 0.01, respectively). In 43 patients with an uninterrupted infliximab regimen, association was found between high FANA (>or= 1/1280) and lower age (p = 0.048) and patient's assessment of infliximab's efficacy (p = 0.014). Three patients developed anti-dsDNA IgG, preceded by high anti-ssDNA IgG levels, and one of them developed a lupus-like syndrome. Neither the initial presence of high FANA levels nor their increase >or= 1/1280 was significantly associated with discontinuation of infliximab. In contrast, at baseline (p = 0.0012) and at the time of infliximab discontinuation (p = 0.0078), anti-ssDNA IgG (>or= 500 arbitrary units) were more frequent in 7 patients who stopped infliximab due to skin or systemic anaphylactoid reactions. CONCLUSION: Monitoring of serum FANA, anti-dsDNA, and anti-ssDNA IgG antibodies provided predictors of lupus-like symptoms and/or anaphylactoid reactions in patients with RA.
16886894 IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein pla 2006 Jul OBJECTIVES: To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy. PATIENTS AND METHODS: We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR). RESULTS: None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy. CONCLUSIONS: The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.
16504992 Are American College of Rheumatology 50% response criteria superior to 20% criteria in dis 2006 Dec OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.
16544925 [Armentarium and strategies for the treatment of rheumatoid arthritis]. 2005 Dec 15 Rheumatoid arthritis is characterized by chronic synovitis resulting in bone and joint destruction in various delays, and ultimately leading to handicap. Remission can be induced at the beginning of the disease. It is well established that slow-acting remitting drugs can efficiently halt radiological progression and improve functional outcome. Besides symptomatic agents (NSAID, steroids, joint injections and synoviorthesis), several long-acting treatment strategies have been proposed based upon methotrexate, alone or in combination with sulfasalazine, hydroxychloroquine, and also anti-TNF agents. Several strategies have been compared according to the disease profile, and suggested that both combination and mainly tight control of the disease clearly improve the clinical, radiological and functional outcomes. The indication of anti-TNF agents is still discussed case by case with respect to treatment failure and risk-benefit ratio at mid and long term. General practitioners should contribute to an early management and regular follow-up by rheumatologists and to general managements of comorbidities.
15892590 Tacrolimus: in patients with rheumatoid arthritis. 2005 Tacrolimus, a hydrophobic macrolide with immunosuppressant properties, has recently been evaluated as a new treatment for adults with active rheumatoid arthritis. Oral tacrolimus 3mg once daily was significantly more effective than placebo in patients with rheumatoid arthritis (RA) who were refractory or intolerant to disease-modifying antirheumatic drugs (DMARDs), according to results from a 6-month, phase III trial; American College of Rheumatology 20 (ACR20) response rates were 27% and 10%. Tacrolimus 3mg once daily was effective in the same patient group in a 12-month, open-label trial; the ACR20 response rate was 38%. Oral tacrolimus 3 mg once daily was effective in combination with established methotrexate therapy in patients with RA in a 6-month, open-label trial. The ACR20 response rate was 53%. Oral tacrolimus 3 mg once daily was generally well tolerated by patients with active RA refractory or intolerant to previous DMARD treatment or when administered as combination therapy in patients with RA on established methotrexate therapy.
17036857 [Clinical reasoning and decision-making in practice. A man with inexplicable joint pain an 2006 Sep 23 A 52-year-old man presented with polyarthritis and was negative for rheumatoid factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of first choice in rheumatoid arthritis. The arthritis disappeared, but the patient developed fever, progressive dyspnoea, appetite loss and weight loss. Upon hospital admission his medication was stopped and community-acquired pneumonia was diagnosed. The fever persisted despite antibiotic treatment. The tentative diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus, based on the change in clinical condition that could not be explained by polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was treated with high-dose steroids and azathioprine and remained in remission for more than 1 year after treatment. The ANA test remained strongly positive, whereas anti-dsDNA was no longer detectable. This case stresses the limited value of classification criteria for the diagnosis of rheumatoid arthritis. To differentiate between rheumatoid arthritis and systemic lupus erythematosus, tests for autoantibodies against citrullinated peptides can be used. To differentiate between systemic lupus erythematosus and infection, tests for anti-dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can be used.
16855168 Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid ar 2006 Jun Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. IN CONCLUSION: Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.
15345497 Expression of resistance markers to methotrexate predicts clinical improvement in patients 2005 Apr BACKGROUND: Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. OBJECTIVE: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. METHODS: The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (-) of RFC and functional (f) MRP. RESULTS: fMRP+/RFC+ and fMRP-/RFC- patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP-/RFC+ group (29%); fMRP+/RFC- patients had a low frequency of good disease activity responses. CONCLUSIONS: Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
16225377 Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. 2005 Infliximab (Remicade) is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-alpha that has shown efficacy in Crohn's disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2 and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmaco-economic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn's disease (including fistulising disease) or rheumatoid arthritis (including early disease).
16511933 Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. 2006 Mar We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.
16091838 Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankyl 2006 Mar Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has been detected increasingly by using highly sensitive diagnostic techniques such as high-resolution computed tomography (HRCT). However, HRCT findings in healthy controls and the effects of smoking and drugs have not been well studied. The aim of this controlled study was to evaluate the relationships between disease-specific clinical, laboratory, HRCT and pulmonary function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS patients using sulphasalazine who were non-smokers and exhibited asymptomatic respiratory signs. For this purpose, a total of 60 persons (40 patients and 20 healthy controls) were included in this study. A restrictive pattern on PFT was detected in four patients (20%) with AS, one patient with RA and one control (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had positive HRCT findings. Only one patient (5%) in the control group had abnormal HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion measurement, the score of the visual analogue scale (VAS) for pain and C-reactive protein (CRP) levels were statistically significantly better in patients with AS having normal HRCT than in those with abnormal findings (p<0.05). There was no correlation detected between HRCT and duration of disease, disease activity markers, functional indexes and PFT in patients with RA and AS. HRCT is a sensitive tool in detecting ILD in patients with RA and AS with no signs and symptoms of pulmonary involvement and may be an integral part of such work-up. However, future prospective studies are needed to better determine if HRCT is in fact a predictor of subsequent MTX toxicity.
15960556 The cost effectiveness of infliximab for severe treatment-resistant rheumatoid arthritis i 2005 OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social service perspectives) of infliximab plus methotrexate (MTX) compared with MTX alone, in the treatment of patients with severe rheumatoid arthritis (RA) who were not adequately controlled on disease-modifying antirheumatic drugs and who were resistant to MTX. METHOD: Clinical data for the first year of therapy were taken from the ATTRACT (Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy) and a Markov model developed to assess costs and consequences in the longer term. Transition probabilities and health state valuations for the model were estimated based on the ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) cohort, and resource use and costs ( 2,000 pounds values) obtained from various sources in the UK. Univariate sensitivity analyses were conducted to test the robustness of the results. RESULTS: The primary analysis suggested that infliximab plus MTX had an ICER of 33,618 pounds per QALY gained. Alternative modelling assumptions and various other sensitivity analyses were applied, but the ICER always remained within the range for interventions typically funded by the NHS. CONCLUSION: This model suggests, with its underlying assumptions and data, that the combination of infliximab and MTX may be a cost-effective treatment (from the UK NHS and personal social service perspectives) for patients experiencing RA that cannot be maintained on MTX alone.
16855169 Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid a 2006 Jun Osteoporosis (OP) occurs more frequently in patients with rheumatoid arthritis (RA) than in healthy individuals. Specific treatments of RA may increase susceptibility to OP, but at the same time decrease inflammatory activity, which is associated with accelerated bone loss. Treatment with TNF-alpha blockers might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular level. Our aim was to assess the influence of anti-TNF-alpha therapy on bone metabolism in RA patients. To that end we evaluated a group of 30 RA patients [mean age 50.6 +/- 6.8 years; median disease duration 82 +/- 38 months; median disease activity score (DAS-28) 5.8 +/- 1.2: 70% of whom were positive for the rheumatoid factor IgM (>40 IU/mL)]. Patients were treated with stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX = 10 mg/week). Eleven of these RA patients further received etanercept (25 mg, twice/weekly) and 10 infliximab (3 mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group included 10 RA patients with stable therapy (prednisone and MTX) and without anti-TNF-alpha therapy. All the patients fulfilled the ACR criteria for the diagnosis of adult RA and were treated for 6 months. Quantitative ultrasound (QUS) bone densitometry was performed at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy). Amplitude-dependent speed of sound (AD-SoS) was evaluated at base line and at 3 and 6 months. Bone mineral density (BMD) of the hip and lumbar spine (L1-L4) was determined by a densitometer (GE Lunar Prodigy, USA) at base line at after 6 months. Soluble bone turnover markers [osteocalcin (BGP) and deoxypyridinoline/creatinine (Dpd/Cr) ratio] were measured in all patients at the same times, using enzyme-linked immunosorbent assay tests. All data were compared using Wilcoxon signed rank test. Results were as follows: AD-SoS values were found increased by 1.3% after 6 months of treatment in the RA patients treated with anti-TNF-alpha therapy. On the contrary, the Ad-SoS levels decreased by 4.6% during the same period in the untreated RA group. BMD increased by 0.2% at lumbar spine and 0.1% at the hip in TNF-alpha-blocker-treated patients and decreased by 0.8% and 0.6% (at lumbar spine and at the hip, respectively) in RA patients without anti-TNF-alpha therapy. However, BMD variations were not significant. In RA patients treated with TNF-alpha blockers, BGP levels were found significantly increased (14.8 +/- 3.8 mg/mL vs. 22.4 +/- 4.2 mg/mL; P < 0.01) and Dpd/Cr levels were found significantly decreased (8.2 +/- 2.1 nM vs. 4.6 +/- 1.8 nM; P < 0.01) at 6 months when compared to base line values. On the contrary, there were no significant differences in the untreated RA patients concerning these latter parameters (BGP = 12.2 +/- 3.1 mg/mL vs. 10.8 +/- 2.8 mg/mL and Dpd/Cr = 8.9 +/- 2.4 nM vs. 10.2 +/- 1.8 nM, respectively). In conclusion, during 6 months of treatment of RA patients with TNF blockers, bone formation seems increased while bone resorption seems decreased. The reduced rate of OP appears to be supported by the same mechanisms involved in the decreased bone joint resorption during anti-TNF-alpha therapy, that is, the marked decrease of the proinflammatory (i.e., TNF-alpha) cytokine effects on bone metabolism.