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ID PMID Title PublicationDate abstract
17009230 Disconnect between inflammation and joint destruction after treatment with etanercept plus 2006 Oct OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.
17471832 [Rational therapeutic approach in rheumatoid arthritis]. 2006 The natural course of rheumatoid arthritis inevitably leads to joint damage and reduced life expectancy. Therefore, active treatment of rheumatoid arthritis is indispensable. Although the etiology still remains unknown resulting in unsuccessful prophylaxis and incurability of rheumatoid arthritis, learning more about its pathophysiology broadens the spectrum of therapeutic possibilities. The aim of treatment is remission of the disease. Current standards of treatment are based on the idea to start aggressive treatment as early as possible to suppress the activity of the disease. This can be achieved by pharmacotherapy and rehabilitation. Physiotherapy is supplementary but there is no room for spa treatment or alternative therapies. Treatment should be introduced immediately because the "window" for successful change in the natural course of the disease covers the first three months since onset. Diagnostic difficulties during this period support the idea of "early arthritis" and "early rheumatoid arthritis". Glycocorticosteroids at a dose suitable to suppress inflammation represent the first-line treatment. Basic therapy which usually is synonymous for methotrexate 15-25 mg once weekly should be introduced from the 4th month at the latest. In case of methotrexate intolerance, leflunomide is an alternative. Lack of efficacy of monotherapy with these drugs mandates the combination therapy of methotrexate with leflunomide, cyclosporine or sulphasalazine together with hydroxychlorochine. The use of two latter drugs should be limited due to their low efficacy. Patients refractory to combination therapy should be considered as candidates to anticytokine drugs or to lymphocyte B depleting drugs. However, it should be emphasized that their high efficacy is achieved only in combination with full doses of methotrexate. The same rules should be applied to therapeutic decisions in elderly patients and in patients with long history of rheumatoid arthritis. However, lower doses of the drugs should be used at initiation of therapy. Contraindications related to side effects and concomitant diseases should be considered. In these groups, glycocorticosteroids play a more important role and cyclophosphamide is used more frequently. Surgical treatment should be reserved for patients with advanced disease. Total joint replacement is an effective method for large joints. Synovectomy should be done only exceptionally when all options of pharmacotherapy were ineffective.
15895898 Serum soluble interleukin-2 receptor predicts early remission in patients with recent-onse 2005 Mar OBJECTIVE: To study the value of baseline serum levels of circulating soluble interleukin-2 receptor (sIL-2R) and soluble E-selectin as predictors of early remission in patients with recent-onset rheumatoid arthritis (RA) receiving a single disease-modifying anti-rheumatic drug (DMARD) (SINGLE) or therapy with a combination of DMARDs (COMBI). METHODS: Baseline (n = 157) serum samples originate from the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, in which 195 patients with early and clinically active RA were randomly assigned to receive either SINGLE (initially sulfasalazine) with or without prednisolone, or COMBI therapy (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone). Of the samples, 76 were from SINGLE patients and 81 from COMBI patients. sIL-2R was measured by automated immunoassay analyzer and sE-selectin by enzyme-linked immunosorbent assay. RESULTS: At six months, 7 (9% [95% CI: 4 to 18]) SINGLE and 19 (23% [95% CI: 15 to 34]) COMBI patients were in remission. In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. The area under receiver operating characteristic curve for sIL-2R level was 0.86 (95% CI: 0.62 to 0.95) in SINGLE and 0.57 (95% CI: 0.42 to 0.71) in COMBI (p = 0.006). In SINGLE, the optimal cut offpoint was 442 U/ml, lower levels predicting remission with sensitivity of 83% (95% CI: 73% to 91%) and specificity of 86% (95% CI: 42% to 100%). Likelihood ratio for positive test was 5.9 (95% CI: 1.6 to 32.8). In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. CONCLUSION: Low baseline serum sIL-2R level predicts early remission of patients with active early RA treated with a single DMARD.
17158693 Treatment of rheumatoid arthritis. 2006 Dec 15 PURPOSE: Current and investigational treatments of rheumatoid arthritis (RA) are described. SUMMARY: The current therapies used to treat RA include nonsteroidal antiinflammatory drugs (NSAIDs), used for the management of pain and inflammation; disease-modifying antirheumatic drugs (DMARDs), used as first-line therapy for all newly diagnosed cases of RA; and biological-response modifiers, targeted agents that selectively inhibit specific molecules of the immune system. Glucocorticoids and other antirheumatic drugs are also used to treat RA. DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. NSAIDs and glucocorticoids are effective in controlling the pain, inflammation, and stiffness related to RA. Unlike NSAIDs, they slow clinical and radiographic progression of RA. The biological-response modifiers include infliximab, etanercept, and adalimumab (inhibitors of tumor necrosis factor [TNF]-alpha); anakinra, a recombinant inhibitor of interleukin-1; abatacept, the first costimulation blocker; and rituximab, a chimeric anti-CD20 monoclonal antibody. Investigational therapies for RA include anti-interleukin-6-receptor monoclonal antibodies, new TNF-alpha inhibitors (including one for oral administration), and antibodies against proteins critical for B-cell function and survival. Data accumulated in the past decade favor early aggressive therapy for patients suspected of having RA, including early referral to a rheumatologist, new diagnostic techniques, and aggressive therapy with DMARDs, glucocorticoids, and biological agents. The benefits of this approach have been demonstrated in clinical trials. CONCLUSION: Pharmacologic treatments of RA include NSAIDs, glucocorticoids, DMARDs, and biological agents. With an improved understanding of the pathophysiology of RA and the evidence from various clinical trials with the agents, early aggressive therapy with a combination of drugs or biological agents may be warranted for the effective treatment of RA.
15564721 B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. 2005 BACKGROUND: During the 1990s evidence emerged to suggest that B lymphocyte depletion in rheumatoid arthritis (RA) might be of major benefit. METHODS AND RESULTS: In 1997 the B lympholytic monoclonal anti-CD20 antibody rituximab became available. Significant clinical efficacy has been demonstrated in RA, initially in open studies at University College London and recently in a multicentre randomised controlled trial. Forty RA patients at University College London have now received in total 75 treatment cycles with rituximab (up to 4 individually) alone or in combination with corticosteroid, cyclophosphamide and/or methotrexate. Ongoing immunodynamic studies of these patients have shed light on a number of questions about both the therapeutic potential of B cell targeting, and the pathogenesis of RA. CONCLUSIONS: The effects of B lymphocyte depletion lend increasing support to the idea that both the inflammatory effector mechanism and the underlying immunoregulatory disturbance in RA are driven by autoantibody rather than T cells.
16923515 EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis r 2006 Aug A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.
15763460 Improvement of refractory rheumatoid arthritis-associated constrictive bronchiolitis with 2005 Apr Rheumatoid arthritis (RA)-associated constrictive bronchiolitis is a severe condition with no established efficient treatment. A 55-year-old woman with seropositive RA developed rapidly progressive constrictive bronchiolitis confirmed by lung biopsy. Her clinical condition worsened despite steroids and azathioprine. Treatment with etanercept-a tumor necrosis factor (TNF)-alpha inhibitor-combined with methotrexate, resulted in a marked improvement of both her clinical condition and pulmonary function tests. Treatment with TNF-alpha inhibitors and methotrexate may be proposed in RA-associated constrictive bronchiolitis, a severe condition hitherto not amenable to improvement.
16783865 Most rheumatologists are conservative in active rheumatoid arthritis despite methotrexate 2006 Jul OBJECTIVE: To evaluate the proportion of patients with rheumatoid arthritis (RA) visiting office-based rheumatologists for persistently active RA despite past or current methotrexate (MTX) treatment, and to describe the management of these patients in France in 2003. METHODS: All French rheumatologists were invited to participate in a cross-sectional postal survey. During a predetermined week, they were to include the first 2 patients seen for RA with a history of past or current MTX treatment. Adequacy of current treatment was assessed based on the 28-joint Disease Activity Score 28 (DAS28) and on current MTX and corticosteroid regimens. RESULTS: Of the 1800 French rheumatologists, 492 returned 838 assessable patient questionnaires. Mean patient age was 58 years and mean time since RA diagnosis was 10 years; 77% of patients were currently taking MTX, and 51% a corticosteroid. High dosages were noted for MTX (> 15 mg/week) in 20% of patients and for corticosteroid therapy (> 10 mg/day) in 5%. Nevertheless, 41% of patients had active RA (DAS28 score 3.2 to 5.1) and 7% had very active RA (DAS28 score > 5.1). The treatment was left unchanged in 78% of patients, and biological therapy was contemplated in only 16% of patients. CONCLUSION: Although half of MTX-treated patients with RA visiting office-based rheumatologists had active or very active disease, a change in treatment was rarely considered.
15319231 Decreased prolactin response to hypoglycaemia in patients with rheumatoid arthritis: corre 2005 Mar OBJECTIVE: To compare basal and stimulated prolactin levels between patients with rheumatoid arthritis and healthy controls, and to assess the effects of antirheumatic treatment on prolactin concentrations. METHODS: Serum prolactin was assessed under basal conditions and during an insulin tolerance test (ITT) in 20 patients with recently diagnosed active rheumatoid arthritis and 20 age and sex matched controls. The patients were reassessed after two weeks' treatment with naproxen and after six months' additional treatment with either sulfasalazine or methotrexate. Disease activity was assessed by the disease activity score (DAS). RESULTS: Basal levels of prolactin were not significantly different between patients with rheumatoid arthritis and controls. Prolactin responses to hypoglycaemia were less in untreated rheumatoid patients than in controls. DAS scores correlated negatively with the area under the curve (AUC) for prolactin concentrations during the ITT. Treatment with naproxen for two weeks did not influence either basal or stimulated prolactin levels. After six months of antirheumatic treatment, prolactin responses to hypoglycaemia increased significantly to levels observed in controls. At the same time point, DAS had improved considerably. The improvement correlated with the increase in AUC of prolactin during the ITT (r = 0.48; p = 0.05). CONCLUSIONS: Patients with active rheumatoid arthritis have a decreased prolactin response to hypoglycaemia induced stress. The response recovers following treatment with antirheumatic drugs.
17065108 Purine metabolism and clinical status of patients with rheumatoid arthritis treated with d 2006 The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.
17165000 Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational 2006 Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.
17058552 Rheumatoid arthritis: new developments in biologic therapy. 2006 Jun With the development of biologic agents our therapeutic approach to rheumatoid arthritis (RA) and inflammatory diseases in general, has dramatically changed within the last few years. Biologic technically means a substance as the product of biologic system and functionally as an agent that targets specific biologic molecule. Recently a number of endogenous antigens have been identified and these are known to activate CD4+ T cells leading to production of cytokines [interleukin (IL)-1, IL-6] and tumour necrosis factor (TNF)-alpha and immunoglobulins like rheumatoid factor and expression of osteoprotegerin ligands that stimulate osteogenesis leading to joint distruction. Rheumatologists and other practitioners are facing a remarkable wave of new therapies for RA like infliximab, adalimumab, atlizumab, etanercept, anakinra, prosorbacolumn, anti-IL-6 agents, IL-10 and inferferon-r. To date combination therapy of methotrexate plus a single biologic has been widely studied with synergistic effect. Etanercept and infliximab are two biologics available in India.
16881109 Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients wi 2006 Aug OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. CONCLUSION: Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease.
16142860 Performance of a rheumatoid arthritis records-based index of severity. 2005 Sep OBJECTIVE: To assess the performance of a rheumatoid arthritis (RA) records-based index of severity (RARBIS) developed by a Delphi panel process in a cohort of patients with RA. METHODS: We reviewed the medical records of 120 RA patients from the New England Veteran's Administration (VA) Healthcare System and collected data on markers of RA disease severity. Markers were refined through a Delphi panel process before developing the RARBIS based on chart review. The RARBIS includes 5 subscales on surgery, radiography, extraarticular manifestations, clinical status, and laboratory values. Factors that were regarded by the Delphi panel as highly related to severity of RA were assigned higher points on the index. We assessed the validity of the RARBIS by comparing it to the intensity of the actual RA treatment that these patients received: low, neither biologic nor disease modifying antirheumatic drug (DMARD) use; moderate, therapy with DMARD such as hydroxychloroquine, gold, or sulfasalazine; high, treatment with stronger DMARD such as methotrexate, azathioprine, leflunomide, and cyclosporine; and very high, use of any biologics. RESULTS: The RARBIS had a range of 0 to 8. All subscales except extraarticular manifestations were statistically significantly related to intensity of RA treatment (chi-square test p
16645968 Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in 2006 May OBJECTIVE: Bisphosphonates inhibit osteoclast activity, which is central to the development of bone damage in rheumatoid arthritis (RA). The aim of this study was to assess whether treatment with zoledronic acid, compared with placebo, could achieve a > or = 50% reduction in the development of new erosions on magnetic resonance imaging (MRI) in patients with early RA. METHODS: In this proof-of-concept study, 39 patients with early RA and clinical synovitis of the hand/wrist were randomized to receive infusions with either zoledronic acid (5 mg) or placebo, administered at baseline and week 13. Patients in both groups received methotrexate (MTX) at a dosage of 7.5-20 mg/week. MRI and plain radiography were performed at baseline and week 26. RESULTS: At week 26, the mean +/- SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid group compared with the placebo group (0.9 +/- 1.63 versus 2.3 +/- 3.09; P = 0.176). The mean +/- SD increase in the number of hand and wrist bones with erosions was 0.3 +/- 0.75 for zoledronic acid compared with 1.4 +/- 1.77 for placebo (P = 0.029). The proportion of patients in whom new MRI-visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group (P = 0.677). The safety profile of zoledronic acid was similar to that of placebo. CONCLUSION: The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA, as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone.
15818697 Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumat 2005 Apr OBJECTIVE: To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment. METHODS: Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial. RESULTS: At week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and C-reactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001). CONCLUSION: Even in patients without clinical improvement, treatment with infliximab plus MTX provided significant benefit with regard to the destructive process, suggesting that in such patients these 2 measures of disease are dissociated.
16572443 Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with si 2006 Apr OBJECTIVE: To determine associations of methotrexate (MTX) efficacy and toxicity with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway enzymes in patients with early rheumatoid arthritis (RA). METHODS: Patients (n=205) with active RA received MTX at an initial dosage of 7.5 mg/week, which was increased to 15 mg/week and combined with folic acid (1 mg/day) after 4 weeks. If the Disease Activity Score in 44 joints (DAS44) was >2.4 at 3 months, MTX was increased to 25 mg/week. MTX efficacy was evaluated at 3 and 6 months and compared for genotypes in 3 analyses: patients with and without good response (DAS441.2), and patients with and without moderate improvement (DeltaDAS44>0.6). The association between MTX-related adverse drug events (ADEs) and genotype was evaluated by comparing genotypes between patients with and without ADEs, specifically pneumonitis, gastrointestinal ADEs, skin and mucosal ADEs, and elevated liver enzyme levels. The following SNPs were analyzed: methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, dihydrofolate reductase (DHFR) -473G>A, DHFR 35289G>A, and reduced folate carrier 80G>A. In case of significant differences, odds ratios (ORs) were calculated. RESULTS: At 6 months, MTHFR 1298AA was associated with good improvement relative to 1298C (OR 2.3, 95% confidence interval [95% CI] 1.18-4.41), which increased with increased copies of the MTHFR 677CC haplotype. In contrast, MTHFR 1298C allele carriers developed more ADEs (OR 2.5, 95% CI 1.32-4.72). CONCLUSION: Patients with MTHFR 1298AA and MTHFR 677CC showed greater clinical improvement with MTX, whereas only the MTHFR 1298C allele was associated with toxicity. In the future, MTHFR genotypes may help determine which patients will benefit most from MTX treatment.
16926650 Interstitial lung disease in rheumatoid arthritis: recent advances. 2006 Sep PURPOSE OF REVIEW: Subsequent to the ATS/ERS consensus classification of idiopathic interstitial pneumonia, non-specific interstitial pneumonia pattern was the dominant pattern in many collagen vascular diseases, which may explain the better prognosis of interstitial pneumonia associated with collagen disease than idiopathic pulmonary fibrosis. Recent papers on rheumatoid arthritis suggest that this is not the same in all collagen diseases, and this paper will review previous data and discuss recent papers. RECENT FINDINGS: In contrast to other collagen diseases, the usual interstitial pneumonia pattern seems to be more common, or at least as common in rheumatoid arthritis. This pathological observation was supported by high-resolution computed tomography findings. In addition to the usual interstitial pneumonia pattern, several types of small airway involvements were frequently observed in rheumatoid arthritis-associated interstitial pneumonia, the prognosis of which is also variable. SUMMARY: Because the usual interstitial pneumonia pattern may be more frequent in rheumatoid arthritis and some data suggest a poor prognosis for rheumatoid arthritis-associated interstitial pneumonia, further studies are required on the prognosis of collagen vascular disease-associated interstitial pneumonia, especially in relation to the pathological pattern. Drug-related interstitial pneumonia should also be considered in rheumatoid arthritis patients on methotrexate or newer drugs such as leflunomide.
16511917 Combination of cyclosporine and leflunomide versus single therapy in severe rheumatoid art 2006 Mar OBJECTIVE: This study assessed the efficacy and safety of combination (COMB) of cyclosporine (CSA) and leflunomide (LEF) versus each drug alone, in the treatment of severe rheumatoid arthritis (RA). METHODS: One hundred six patients with active RA refractory to at least one disease modifying antirheumatic drug (methotrexate obligatorily) were entered into a 12-month open, prospective trial and were randomly allocated to receive either CSA 2.5 to 5 mg/kg/day, or LEF 20 mg/day, or the combination of both at the same initiating dose. RESULTS: The American College of Rheumatology 50% (ACR50) response rates for the 3 groups were COMB 80%, CSA 40%, and LEF 42% (p = 0.001). Combination therapy was also significantly better than CSA and LEF at the more stringent 70% response rate (69% vs 34% vs 30%, respectively; p = 0.001). Comparable Disease Activity Score 28 reduction rates were noted at trial termination for all 3 treatment arms: COMB -2.74 vs CSA -2.53 vs LEF -2.28 (p nonsignificant). Discontinuation rates were more common in LEF vs CSA arm (p = 0.046). No unexpected or serious adverse drug effects were identified in the combination group during the 12-month period. CONCLUSION: The combination of CSA and LEF in patients with refractory RA provided statistically significant benefit in ACR50 and ACR70. Adverse events were not substantially increased.
16633926 Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid arthritis 2006 The tumor necrosis factor (TNF) antagonist etanercept is an antirheumatic agent which was approved by Japanese regulatory authorities in January 2005. In Japan, the cost-effectiveness of this therapy for patients with rheumatoid arthritis (RA) has not previously been evaluated. This study models the cost-utility of etanercept in comparison with standard therapy with disease-modifying antirheumatic drugs (DMARDs) among adult Japanese RA patients who have failed a previous course of the DMARD bucillamine. A Markov model with 6-month cycles was constructed to compare two therapeutic strategies: etanercept versus standard therapy. For each cycle, one of three options was possible: a patient could (i) remain on current therapy if American College of Rheumatology criteria for 20% clinical improvement (ACR20) were achieved, (ii) switch to another drug in the therapeutic pathway if ACR20 was not achieved or if side effects severe enough to cause treatment discontinuation occurred, or (iii) they could die. The therapeutic pathway for the etanercept strategy was etanercept, methotrexate (MTX), sulfasalazine (SSZ), combination therapy (MTX + SSZ) and, finally, no DMARD. The pathway for standard therapy was identical except the initial therapy was MTX (etanercept was excluded). Results from clinical trials in U.S. and European patient populations were used to derive model probabilities for disease progression, response to drug therapy, and relationships between ACR20 response and functional improvement as measured by the Health Assessment Questionnaire (HAQ) disability index. An equation was developed to predict utility from HAQ scores of Japanese patients. Costs for drugs and medical services in Japan were obtained for April 2003. Analysis was conducted from a societal perspective, including lost productivity costs due to RA disability and premature mortality. Costs were discounted at 6% annually, and quality-adjusted life years (QALYs) at 1.5% annually. Model parameters were varied by 20% above and below base-case values in sensitivity analyses. Compared to standard therapy, the etanercept strategy was yen6.39 million more costly per patient but yielded an additional 2.56 QALYs. The incremental cost-utility ratio was yen 2.50 million/QALY. Sensitivity analyses revealed that cost-utility was most strongly influenced by the acquisition cost of etanercept and the percentage of etanercept recipients who achieved ACR20. Using commonly applied thresholds for acceptable cost-effectiveness in the United States ($50 000 = yen 5.5 million/QALY) and the United Kingdom (pound 30 000 = yen 5.7 million/QALY), etanercept therapy in Japan can be considered cost-effective. Cost-utility ratios did not exceed these thresholds in any sensitivity analysis. Further analyses should be conducted once clinical and epidemiologic data for Japanese patients become available.