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ID PMID Title PublicationDate abstract
18050208 Disease remission and sustained halting of radiographic progression with combination etane 2007 Dec OBJECTIVE: The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. METHODS: In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate < or =20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. RESULTS: Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. CONCLUSION: Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA.
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.
18930988 Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus me 2009 Jul OBJECTIVES: To compare the clinical and radiological efficacy of initial vs delayed treatment with methotrexate (MTX) and infliximab (IFX) in patients with recent onset rheumatoid arthritis (RA). METHODS: In a post hoc analysis of the BeSt study (for Behandel Stratagieen, Dutch for treatment strategies), 117 patients who started initial MTX+IFX were compared with 67 patients who started MTX+IFX treatment after failing (disease activity score (DAS)>2.4; median delay to IFX: 13 months) on > or =3 traditional DMARDs. If the DAS remained >2.4, the protocol dictated IFX dose increases to 6, 7.5 and 10 mg/kg. In case of a DAS < or =2.4 for > or =6 months, IFX was tapered and finally stopped. We aimed to correct for allocation bias using propensity scores. Functional ability was measured by the Health Assessment Questionnaire (HAQ), radiological progression by Sharp/van der Heijde scoring (SHS). RESULTS: Baseline differences between the initial and delayed groups were no longer significant after propensity score adjustment. At 3 years after baseline, patients treated with initial MTX+IFX experienced more improvement in HAQ over time and were less likely to have SHS progression than patients treated with delayed MTX+IFX (p = 0.034). At 2 years after IFX initiation, more patients in the initial group compared with the delayed group could discontinue IFX after a good response (56% vs 29%, p = 0.008). CONCLUSIONS: The results of this post hoc analysis suggest that using MTX+IFX as initial treatment for patients with recent onset RA is more effective than reserving MTX+IFX for patients who failed on traditional DMARDs, with more HAQ improvement over time, more IFX discontinuation and less progression of joint damage.
17922664 Understanding the mechanisms of action of methotrexate: implications for the treatment of 2007 Methotrexate has been widely used for the treatment of rheumatoid arthritis (RA). The mechanisms of action of methotrexate are complex. Developed as a folic acid analogue, methotrexate inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Recently, many studies have focused on the adenosine-mediated antiinflammatory effects of methotrexate. Certain aspects of methotrexate toxicities are also attributed to adenosine release. A better understanding of the mechanisms of action and toxicities of methotrexate will direct clinicians in their treatment approach and toxicity monitoring. Toward that objective, the latest developments in the pharmacokinetics, mechanism of action, pharmacogenetics, and toxicity of methotrexate are herein discussed.
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.
18975346 Certolizumab pegol plus methotrexate is significantly more effective than placebo plus met 2008 Nov OBJECTIVE: To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol (a novel PEGylated anti-tumor necrosis factor agent) as adjunctive therapy to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with an inadequate response to MTX therapy alone. METHODS: In this 52-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 982 patients were randomized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0, 2, and 4, with a subsequent dosage of 200 mg or 400 mg given every 2 weeks, plus MTX, or placebo plus MTX. Co-primary end points were the response rate at week 24 according to the American College of Rheumatology 20% criteria for improvement (ACR20) and the mean change from baseline in the modified total Sharp score at week 52. RESULTS: At week 24, ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8% and 60.8%, respectively, as compared with 13.6% for the placebo group. Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 (P < 0.001). At week 52, mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg (0.4 Sharp units) or 400 mg (0.2 Sharp units) as compared with that in placebo-treated patients (2.8 Sharp units) (P < 0.001 by rank analysis). Improvements in all ACR core set of disease activity measures, including physical function, were observed by week 1 with both certolizumab pegol dosage regimens. Most adverse events were mild or moderate. CONCLUSION: Treatment with certolizumab pegol 200 or 400 mg plus MTX resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited the progression of structural joint damage, and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX.
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.
17214933 [Predictive role of diagnostic information in treatment efficacy of rheumatoid arthritis b 2007 Jan OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine (WM) treated group, 194 cases; and traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete physical examination and 18 common clinical manifestations were prepared before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment. The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. The relationships between each variable and efficacy were analyzed, and the variables with P<0.2 were included for the data mining analysis with neural network model. All data were classified into training set (75%) and verification set (25%) for further verification on the data-mining model. RESULTS: Eighteen variables in CM and 24 variables in WM were included in the data-mining model. In CM, morning stiffness, swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint pain were positively related to the efficacy, and disease duration and more urination at night negatively related to the efficacy. In WM, erythrocyte sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint stiffness and swollen joint were positively related to the efficacy, and yellow fur in tongue, red tongue, white blood negatively related to the efficacy. In the analysis with the neural network model in the patients of verification set, the predictive response rates of 20% patients would be 100% and 90% in the treatment with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on the full clinical trial data with collection of both traditional Chinese medicine and modern medicine diagnostic information, shows a good predictive role for the information in the efficacy in rheumatoid arthritis.
18493770 Improved rheumatoid digital vasculitis in a patient treated with TNFalpha agent blocking ( 2008 Oct Rheumatoid vasculitis (RV) is an uncommon but potentially catastrophic complication of rheumatoid arthritis (RA). There are few current extensive studies and no consensus regarding the clinical, laboratory, histologic features and management or prognosis of RV. We report a case of RV in a 74-year old woman with a long (14 years) history of RA, who developed vasculitis of distal arteries with gangrene of digits of upper and lower extremities. After the failure of various immunosuppressive drugs (cyclophosphamide, methotrexate), the patient was treated with anti-TNFalpha infliximab. Digital gangrene healed within four months from the start of anti-TNFalpha treatment.
18034202 Infection of total hip prosthesis by Mycobacterium tuberculosis and Mycobacterium chelonae 2008 Apr Atypical mycobacterial infections of the musculoskeletal system are very rare and are generally associated with predisposing factors, such as trauma, use of corticosteroids, or an immunocompromised state. There have only been three reports of Mycobacterium chelonae prosthetic infection of which two cases were associated with total hip arthroplasty and one with total knee arthroplasty and no reports of both Mycobacterium tuberculosis and M. chelonae occurring in the same joint. We report a case of a patient with rheumatoid arthritis treated with low-dose methotrexate (15 mg/week) who developed infection with both M. tuberculosis and M. chelonae after the revision of a prosthetic hip. Joint infections by mycobacteria are clinically indistinguishable from those caused by more common bacterial pathogens and, therefore, diagnosis is often delayed. Recurrent prosthetic hip infections, particularly in immunosuppressive patients, should alert the physician to consider the possibility of both tuberculous and atypical mycobacterial infections. Obtaining appropriate cultures can be critical in making the diagnosis and directing treatment. With the increasing use of immunosuppressive agents, including TNF alpha inhibitors, it is likely that there will be an increase in the number of mycobacterial infections complicating arthroplasties.
17209660 Inhibiting costimulatory activation of T cells : a viable treatment option for rheumatoid 2007 There is now good evidence that T cells play a central role in the inflammatory pathway that leads to the persistent synovitis that causes joint damage in rheumatoid arthritis (RA). T cells require two signals to become activated. The second step in the activation of T cells involves costimulatory pathways, the best described pathway being the binding of CD28 on T cells to CD80/86 on antigen-presenting cells. This observation has led to the development of a new category of biological response modifier. Abatacept is a fusion protein (cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin [CTLA4Ig]); which blocks the binding of CD28 by avidly binding CD80/86. Without this costimulatory activation, the T cell becomes anergic. Abatacept has consistently been shown to improve the signs and symptoms of RA in phase II and phase III trials in patients with an inadequate response to methotrexate and anti-tumour necrosis factor (TNF) therapy. Onset of action is rapid and efficacy is maintained during the period of treatment. Recent trials have also provided evidence of improvement in quality-of-life measures and radiographic progression. The safety profile to date has also been favourable and supports the theory that targeting naive T cells early in the inflammatory pathway will lead to immunomodulation rather than immunosuppression. The evidence produced so far suggests that abatacept will be a useful addition to the available therapies for patients with RA.
18177923 Characteristics and outcome of connective tissue diseases in patients with sickle-cell dis 2008 Dec OBJECTIVES: To analyze the main characteristics of adults with sickle cell disease (SCD) and concurrent connective tissue disease (CTD). METHODS: A retrospective investigational study was performed. CTD was diagnosed according to standard international criteria. Severity of SCD was assessed by a clinical severity score. RESULTS: Thirty patients, 23 women (76%) and 7 men, with hemoglobin S/S (n = 25) or S/C (n = 5) SCD were included. The subtypes of CTD were rheumatoid arthritis (RA) (n = 15), definite systemic lupus erythematosus or "incomplete lupus" requiring treatment (n = 13), primary Sjögren's syndrome with central nervous system involvement (n = 1), and systemic sclerosis (n = 1). Twenty-five of the 30 patients (83%) received steroid treatment, and 15 (50%) received at least 1 immunosuppressive agent (methotrexate in 14 cases) to control CTD. Four RA patients were given antitumor necrosis factor (TNF)alpha and 1 was treated with rituximab without SCD exacerbation. After a median follow-up of 4.5 years [range: 6 months to 30 years] from CTD diagnosis, 11 of the 25 (44%) patients receiving steroids had at least 1 episode of severe infection (mostly due to Staphylococcus aureus or Escherichia coli). SCD exacerbated in 13 of the 30 (43%) patients after CTD onset; 12 of these patients were receiving prednisone and/or methotrexate. Six patients (20%) had died from sepsis (n = 2), stroke (n = 2), or acute chest syndrome (n = 2). CONCLUSIONS: CTD-related clinical manifestations and outcome were not particularly severe in patients with SCD. However, those with active CTD and undergoing steroid +/- methotrexate treatment had more serious SCD-related manifestations, a higher rate of severe infections, and an overall patient mortality rate of 20%. Thus, the management of patients with CTD and underlying SCD should consider the risk/benefit ratio of each treatment and steroid-sparing strategies should be implemented.
17364080 The use of biological agents in the treatment of rheumatoid arthritis. 2007 Feb Rheumatoid arthritis is a common and potentially devastating condition which did not have good treatment options until recently. Pharmacological treatment should not just comprise antiinflammatory agents and corticosteroids. The current therapeutic approach is to start a disease modifying agent early in the illness to prevent eventual joint damage. Older disease modifying anti-rheumatic drugs (DMARDs) include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporine are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents which block certain key molecules involved in the pathogenesis of the illness. They include tumour necrosis factor (TNF)- blocking agents such as infliximab, etanercept and adalimumab, the anti-CD 20 agent rituximab and CTLA-4 Ig abatacept. Other agents which are in development include anti-IL6 tocilizumab, anti-CD22 and anti-lymphostat B. In this review, the efficacy and side effects of these agents, their impact on current clinical practice and future trends are discussed.
17502830 Validation of the associations between single nucleotide polymorphisms or haplotypes and r 2007 Jun BACKGROUND: For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized adverse events. METHODS: We conducted retrospective studies to validate our previous three different results about the association between adverse events or efficacy of two different disease-modifying antirheumatic drugs and genomic variations. Association between single nucleotide polymorphisms in N-acetyltransferase 2 gene (NAT2) and adverse events by sulfasalazine and association between C677T or A1298C in 5,10-methylenetetrahydrofolate reductase gene (MTHFR) and responses to methotrexate were examined. RESULTS: Patients without the wild-type haplotype at NAT2 were more likely to suffer from overall adverse events [n=186, P=0.001, relative risk (RR) 3.31, 95% confidence interval (CI) 1.76-6.22] and severe adverse events (P=0.015, RR 24.6, 95% CI 2.37-254.53) by sulfasalazine. Patients with the T allele at C677T in MTHFR were more susceptible to overall adverse events (n=156, P=0.003; RR 2.4, 95% CI 1.29-4.55) while patients with the C allele at A1298C were less likely to be treated with a higher dose (>6 mg/week) of methotrexate in one year of treatment (n=159, P=0.008, RR 1.84, 95% CI 1.12-3.01). In all three association studies, the results were essentially the same as previously reported. CONCLUSION: As three studies on the associations between genomic variations and adverse events or efficacy of two different disease-modifying antirheumatic drugs were replicated, the usefulness of the tests is worth being tested in clinical practice.
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.
18509240 Application of fluorescence polarization immunoassay for determination of methotrexate-pol 2008 May Rheumatoid arthritis (RA) is a chronic disease characterized by the painful joints, inflammation, uncontrolled proliferation of synovial tissue and multisystem comorbidities. Weekly low-dose methotrexate (MTX) has been established as effective treatment in RA patients. MTX is converted to gamma-glutamyl polyglutamates, an active form of MTX, through the action of folylpolyglutamate synthetase in the cells. MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) may be useful as a therapeutic marker of RA. However, the previously reported methods for the quantification of MTX and MTX-PGs in RBCs are impractical for clinical use due to time-consuming, laborious and high cost. We attempted to apply a method with the commercially available fluorescence polarization immunoassay (FPIA) kit. We found that anti-MTX monoclonal antibody showed the reactivity to 4-amino-10-methylpteroylheptaglutamic acid (MTX-PG(7)) as equal to MTX. Good agreement was observed in the concentration-response curves between MTX and MTX-PG(7) spiked samples. Accordingly, the anti-MTX monoclonal antibody for FPIA appeared to show the equal reactivity to MTX and MTX-PGs. The recoveries of MTX and MTX-PG(7) from RBCs were 99.0% and 94.1%, respectively. Furthermore, we determined total MTX-PGs concentrations in RBCs of 71 patients with RA treated with weekly pulse MTX. Total MTX-PGs concentrations in 70% of the patients were found to be more than 50 nM that is the lower limit of MTX-PGs concentration in RBCs for expected therapeutic outcome. The routine measurement of total MTX-PGs concentration in RBCs might be useful for prediction about therapeutic outcome of MTX in RA patients.
17341506 Assessing remission in clinical practice. 2007 Jun OBJECTIVE: Remission constitutes the best achievable state in patients with rheumatoid arthritis. We aimed at evaluating sustained remission in a large cohort of patients followed prospectively in clinical practice and to evaluate available instruments to define remission for their stringency in defining this state. PATIENTS AND METHODS: We analysed remission and sustained remission in 621 patients who had two consecutive and complete clinical observations; the average period between the two visits was 92 days (median; quartiles: 82; 105). Remission was evaluated according to modified ACR (mACR), 28 Joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) criteria. Sustained remission was defined as remission at both consecutive visits. Patients were treated with traditional disease- modifying antirheumatic drugs, mainly methotrexate, and partly with biological agents (approximately 11%). RESULTS: Remissions at any one of the two visits were seen in 33.5% of patients by SDAI or CDAI, 42.7% by DAS28, and 38.6% by mACR criteria (P < 0.01). Sustained remission was observed in much lower proportions of patients (between 16.7 and 19.6%, dependent on the instrument). Agreement between classifications of remission by kappa-statistics was very good for SDAI vs CDAI, good for DAS28 vs SDAI or CDAI, and only moderate for mACR vs the three other scores. Residual swollen joints were observed in 15% of patients in DAS28 remission (range 1-9), 6% of patients in mACR remission (range 1-8), but only approximately 5% of patients in CDAI or SDAI remission (range 1-2) (P < 0.01). CONCLUSION: Sustained remission can be observed in 17-20% of patients in clinical practice. CDAI and SDAI remission criteria are more stringent than DAS28 and mACR criteria, since they allow for lesser residual disease activity. Consequently, smaller proportions of patients are classified as in remission by SDAI and CDAI than by DAS28 and mACR criteria. Sustained remission is an achievable goal in clinical practice even with the most stringent of the definitions studied.
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.