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12180722 Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative 2002 Aug OBJECTIVE: The use of disease modifying antirheumatic drugs (DMARD) for rheumatoid arthritis (RA) is predicated on the expected value of the treatment course. Most clinical data are generalized from randomized controlled trials (RCT), which may result in estimates that are discordant with clinical experience and cannot address the effects of sequence of drugs. We computed estimates of relative DMARD effectiveness from a large observational database using area under the curve (AUC) data. METHODS: We examined data collected over a 20 year period on 1160 patients who were followed at the Wichita Arthritis Center. We utilized Health Assessment Questionnaire (HAQ) disability index data to quantify the effect of methotrexate (MTX), hydroxychloroquine (HCQ), and injectable gold (gold) on subsequent patient outcome. Using an AUC analysis, we compared length of treatment course, total disability averted, annual disability averted, and percentage of possible disability averted across drugs, and examined differences between first courses of therapy in DMARD naive patients and subsequent courses of the same and different DMARD in patients. RESULTS: Patients treated with MTX, HCQ, and gold improved at a rate of -0.33, -0.18 and -0.38 annualized HAQ area units, respectively. Since duration taking drug was greatest for MTX, then HCQ, then gold, the cumulative improvement was greatest with MTX (-1.07) versus gold (-0.74) versus HCQ (-0.47) in disability unit years. All 3 drugs were better cumulatively with earlier disease (MTX-1.74 for < 1 yr vs -0.95 for > 1 yr; HCQ -0.68 vs -0.43; gold -1.71 vs -0.49). A second trial of the same drug was far less effective than the first course. On a percentage of possible improvement basis, these drugs were nearly equal since HCQ is given to less severely affected patients. CONCLUSION: MTX is the most effective DMARD of these 3 because of the length the therapeutic segment. In terms of disability averted, none of the agents decrease disability by more than 25% of the theoretically possible improvement. We documented that effectiveness of RA treatment is a function of drug sequence, duration of disease, whether it is a first or second course, and severity of disease. None of these clinically relevant observations have emerged from clinical trials. These methodologic approaches provide important quantitative comparative data and will be useful in further assessment of the relative effectiveness of present and future DMARD.
15334458 In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatme 2004 Aug OBJECTIVE: Sensitive noninvasive strategies for monitoring treatment response in rheumatoid arthritis (RA) would be valuable for facilitating appropriate therapy and dosing, evaluating clinical outcome, and developing more effective drugs. Because different proteases are highly up-regulated in RA and contribute significantly to joint destruction, in the present study we investigated whether such enzymes are suitable in vivo imaging biomarkers for early evaluation of treatment response in a murine model of RA. METHODS: Using a protease-activated near-infrared fluorescence (NIRF) imaging "smart" probe, we examined the presence and distribution of fluorescence in arthritic joints of mice with collagen-induced arthritis by both noninvasive fluorescence imaging and histology. Proteases that target the Lys-Lys cleavage site, including cathepsin B, activate probe fluorescence. Treatment monitoring data were obtained following methotrexate (MTX) therapy. RESULTS: Twenty-four hours after intravenous injection of the protease sensor, affected toes and paws of arthritic mice showed significantly higher fluorescence intensity than did toes and paws of healthy mice. Fluorescence from the protease probe and cathepsin B antibody histologic staining were localized in the vast majority of cells in the inflamed synovium. In arthritic animals treated with MTX (35 mg of MTX/kg 48 hours prior to probe injection), a significantly lower fluorescent signal (inflamed paws 50%, inflamed toes 70%) was observed as compared with untreated arthritic animals. CONCLUSION: Protease-activated NIRF probes are sensitive means of imaging the presence of target enzymes in arthritic joints and can be used for early monitoring of treatment response to antirheumatic drugs such as MTX.
15487808 The MDR1 3435 polymorphism in patients with rheumatoid arthritis. 2004 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, the pathogenesis of which involves immunological, genetic and environmental factors. P-glycoprotein (P-gp) encoded by the MDR1 gene, is an important transporter for many drugs, xenobiotics and cytokines and may be associated with many immunological processes and apoptosis. The activity of P-gp is genetically determined. Naturally occurring MDR1 polymorphisms have been described and correlated with potential clinical effects. Several mutations in the MDR1 gene have been recognized, but only some of them are associated with P-gp expression. The C3435T polymorphism was found to correlate with the activity of P-glycoprotein. The aim of the study was to evaluate the C3435T MDR1 polymorphism in patients with rheumatoid arthritis and to investigate a possible correlation with disease susceptibility, activity and severity. METHODS: The study was carried out in 92 patients with rheumatoid arthritis and 97 healthy subjects as a control group. The C3435T polymorphism was determined using the PCR-RFLP method. RESULTS: The distribution of C3435TT MDR1 genotypes in RA patients did not differ significantly from that in a control group and was as follows: 3435CC in 25 (26.9%) subjects, 3435CT in 50 (53.8%) and 3435TT in 17 (18.3%). The probability of remission of RA symptoms after therapy with methotrexate and glucocorticosteroids however, was 2.89-fold greater in patients with the 3435TT genotype compared to patients with the genotypes 3435CC and 3435CT. The risk of having an active form of rheumatoid arthritis resistant to therapy with disease-modifying antirheumatic drugs in patients with 3435CC and 3435CT genotypes was 2.89 times greater than in homozygous 3435TT subjects. CONCLUSION: We suggest that the C3435T MDR1 polymorphism is not an important genetic risk factor for RA susceptibility, but that this polymorphism may have an influence on the activity of the disease and its response to therapy with disease-modifying antirheumatic drugs.
15206742 Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis dur 2003 The kynurenine pathway from tryptophan generates compounds which can act on glutamate receptors in peripheral tissues or modulate free radical activity. We have measured the concentrations of several of these compounds in the plasma of patients with rheumatoid arthritis (RA) and osteoporosis (OP) before treatment with drugs and then at monthly intervals for 6 months during treatment. Kynurenine analysis was performed by HPLC. Compared with healthy controls, RA patients showed significantly decreased baseline levels of tryptophan, 3-hydroxykynurenine and 3-hydroxyanthranilic acid and increased levels of kynurenine and xanthurenic acid, while kynurenic acid concentrations were normal. Different results were recorded from patients with OP with only a significant reduction in tryptophan and 3-hydroxyanthranilic acid when compared with healthy controls. During 6 months of treating the RA patients with prednisolone or methotrexate, and the OP patients with raloxifene or etidronate and calcium there were significant therapeutic responses and a significant trend towards a reduction in levels of neopterin in RA patients receiving methotrexate but no changes in the profiles of tryptophan metabolites. The results are consistent with the induction of indoleamine-2,3-dioxygenase (IDO) in both RA and OP but with far greater activation of the pathway in the much more inflammatory condition, i.e. RA. It is concluded that there are changes in the kynurenine pathway, which may modify the activation of tissue glutamate receptors, in RA and OP, but that these are not affected by the drug treatments studied.
11953964 Delay to institution of therapy and induction of remission using single-drug or combinatio 2002 Apr OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.
15124248 Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid 2004 May OBJECTIVE: To determine cost-effectiveness of folic or folinic acid supplementation in patients with rheumatoid arthritis (RA) who started methotrexate (MTX) treatment. METHODS: An economic evaluation, performed alongside a randomized, double blind, placebo controlled trial with followup of 48 weeks. Patients started MTX with placebo (n = 137), folic acid (n = 133), or folinic acid (n = 141). Outcome measures were drug survival and quality-adjusted life-years (QALY), measured with the EuroQol questionnaire. Both medical and nonmedical costs were analyzed. RESULTS: Drug survival after 48 weeks was 60% for placebo, 81% for folic acid, and 87% for folinic acid. QALY during a 48 week period were 0.55 (95% CI 0.52-0.58) in the placebo group, 0.55 (95% CI 0.52-0.58) in the folic acid group, and 0.58 (95% CI 0.56-0.60) in the folinic acid group. Mean medical costs were 1398 US dollars (placebo), 1409 US dollars (folic acid), and 1776 US dollars (folinic acid). Mean total costs were 3339 US dollars, 3632 US dollars, and 3296 US dollars, respectively. CONCLUSION: In terms of resource deployment, no statistically significant difference was found between the 3 strategies. The preferred strategy consists of folic acid supplementation because of improved drug survival.
12942699 Early onset and effective inhibition of bone resorption in patients with rheumatoid arthri 2003 Jul OBJECTIVE: To investigate the effect of the tumour necrosis factor alpha antibody infliximab on bone metabolism in patients with rheumatoid arthritis (RA). METHODS: Twelve RA patients with active disease on a constant dose of methotrexate were treated with a single infusion of infliximab (10 mg/kg BW). Serum beta-CrossLaps and serum osteocalcin as markers of bone resorption and formation were measured two days and one day before and one and 14 days after infliximab infusion with an electrochemiluminiscence immunoassay. RA disease activity was determined using the Disease Activity Score (DAS) and the ACR-response criteria. RESULTS: Infliximab treatment significantly reduced serum beta-CrossLaps levels from 0.29 +/- 0.13 (mean +/- SD) ng/ml at study entry to 0.17 +/- 0.09 pg/ml one day after infusion (p < 0.005). At day 14 serum beta-CrossLaps levels were still significantly lower compared to pre-treatment levels (0.24 +/- 0.13 pg/ml, p < 0.05). In contrast, serum osteocalcin levels remained unchanged during the observation period (17.8 +/- 9.8 vs 18.2 +/- 9.9 vs 18.6 +/- 12.1 ng/ml, respectively). All but one patient improved clinically after infliximab infusion and the DAS dropped significantly from 6.5 +/- 0.9 prior to treatment to 5.8 +/- 1.3 and 5.0 +/- 1.3 at Day one and 14 days after treatment, respectively. Four patients showed an ACR 20-response one day after therapy and 10 patients 14 days after therapy. CONCLUSION: Infliximab might have potential to inhibit generalised bone loss in patients with RA in addition to its clinical efficacy in reducing disease activity and inhibiting joint destruction.
15240743 IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross- 2004 Jul 15 To characterize the molecules responsible for synovial fibroblast-T lymphocyte (TL) cross-talk in rheumatoid arthritis (RA), synovial fibroblasts from patients with established RA (RASFibs) were cocultured with TLs from peripheral blood of early RA patients (RAPBTL). TLs from peripheral blood of healthy controls and from synovial fluid of RA served as controls. Adhesion molecules and cytokines were determined by flow cytometry, ELISA, and real-time PCR. RAPBTL (n = 20) induced an up-regulation of ICAM-1, intracellular IL-8, IL-6, IL-15, and surface IL-15 in cocultured RASFibs. In turn, RAPBTL showed an up-regulation of TNF-alpha, IFN-gamma, IL-17, CD25, and CD69 expression. Responses seen with TLs from peripheral blood of healthy controls (n = 20) were significantly lower, whereas responses with TLs from synovial fluid of RA (n = 20) were maximal. Blocking Abs to IL-15 and CD54, but not an isotype-control Ab, down-regulated the increased TL cytokine and activation marker expression. Abs to CD69, CD11a, IL-17, TNF-alpha, and IFN-gamma significantly decreased the up-regulation of RASFib cytokine and CD54 expression. Cocultures using 0.4- micro m inserts did not result in up-regulation of surface molecules or cytokines. Methotrexate significantly inhibited RASFib/TL cross-talk signals and decreased adhesion of TL to RASFibs. In summary, RASFib production of IL-15 induces the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-17 in cocultured TLs through a cell contact-dependent mechanism. In turn, these cytokines stimulate the expression of IL-15, IL-8, and IL-6 in RASFibs, thereby creating a feedback loop that favors persistent synovial inflammation. Methotrexate seems to disrupt this loop by decreasing cell adhesion.
12102473 Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid a 2002 May OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.
11840436 COBRA combination therapy in patients with early rheumatoid arthritis: long-term structura 2002 Feb OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. METHODS: All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.
11817993 Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: 2002 OBJECTIVE: To compare disease-related medical care and productivity costs, and utilities, in 482 patients with rheumatoid arthritis randomised to receive leflunomide, methotrexate or placebo during a 12-month period. DESIGN AND SETTING: Prospective pharmacoeconomic analysis of a 1-year randomised double-blind trial set in North America. PERSPECTIVE: Societal and the Ontario Ministry of Health. METHODS: Information on healthcare resources, out-of-pocket expenses, loss of working time and time spent on chores, related to the disease or the medication, were collected at 4-week intervals and at study discontinuation. Rating scale and standard gamble (SG) utilities (0 = worse; 100 = best) were collected at baseline and at 6 and 12 months or study exit. Medical care costs in Canadian dollars (Can dollars) were calculated using Ontario reimbursement schedules. US patients' expenses were converted to Can dollars using 1995 purchasing power parity. Lost wages were calculated by age and gender according to 1995 Canadian wage data. All costs were adjusted to 1999 Can dollars and arithmetic mean costs were compared using the nonparametric bootstrap. Analysis of covariance was performed to compare utilities between groups. RESULTS: Mean (standard deviation) rating scale values and SG utilities, respectively, for leflunomide, methotrexate and placebo were 67.7 (18.0), 64.8 (18.1) and 57.5 (9.2), and 80.2 (22.1), 83.2 (18.0) and 77.0 (20.5). Both leflunomide and methotrexate had higher rating scale values (p < 0.05) compared with placebo; SG utilities were significantly different between methotrexate and placebo (p < 0.05). Annualised total rheumatoid arthritisb- or drug-related costs for leflunomide, methotrexate and placebo, respectively, were Can dollars 1761, Can dollars 1280 and Can dollars 1324, and medical care costs were Can dollars 753, Can dollars 620 and Can dollars 167 (all costs exclude drug acquisition and monitoring costs). Annual drug acquisition/ routine monitoring costs were estimated, respectively, at Can dollars 3853/Can dollars 483 for leflunomide and Can dollars 258/Can dollars 599 for methotrexate. Differences between overall costs (excluding drug acquisition and monitoring costs) and medical care costs were not statistically significant. The costs of treating patients with leflunomide were significantly higher than for methotrexate when drug acquisition and monitoring costs were included (p < 0.0001). CONCLUSIONS: No statistically significant differences in utilities could be found between leflunomide or methotrexate. When drug monitoring and acquisition costs are excluded, leflunomide has an otherwise similar economic profile compared with methotrexate, the current gold standard. The acquisition cost of leflunomide is a driving factor in increasing the costs of therapy. These higher costs need to be assessed relative to the therapeutic value of leflunomide.
15552522 Benefit/risk of cyclosporine in rheumatoid arthritis. 2004 Sep Combination therapy has emerged as a crucial therapeutic tool to control aggressive rheumatoid arthritis (RA). Cyclosporine (CsA) when combined with methotrexate (MTX) has shown substantial benefit in clinical practice. The primary benefit is its positive effect in the control of joint-bone erosions. The most feared adverse effect is the development of nephrotoxicity, which may be in part hemodynamic and in part structural, i.e. fibrotic. Careful monitoring of concomitant drugs, hypertension and through blood levels should allow the patient to maintain normal renal function. The successful employment of CsA in lupus nephritis clearly supports this statement.
15352425 Health care and burden of illness in systemic lupus erythematosus compared to rheumatoid a 2004 During the past 20 years, outcome studies in the rheumatic diseases have, on the one hand, given increasing evidence of the unfavourable long-term prognosis of rheumatoid arthritis (RA) and on the other hand determined continuous improvement of prognosis in systemic lupus erythematosus (SLE). The aim of the study was to investigate how this translates into the current spectrum of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) seen by rheumatologists in Germany and to compare aspects of the burden of disease, disease outcomes and treatment between these two important rheumatic diseases using a large clinical database. Current health care was analysed with data from the German rheumatological database of 10 068 patients with RA and 1248 patients with SLE seen by rheumatologists in 2001. In addition, of a total of 3546 patients with SLE and 24 969 patients with RA seen at the German Collaborative Arthritis Centres between 1994 and 2001, 3465 cases of SLE were matched by age, sex, disease duration and referral status with a corresponding RA case. There were considerable differences in treatment of patients before referral to a rheumatologist and in rheumatologic care. In 2001, patients with SLE were treated by their rheumatologists mainly with antimalarials (AM, 37%), azathioprine (29%) and nonselective NSAIDs (16%). Of them, 61% received at least one immunosuppressive drug (including AM) plus glucocorticoids. In RA, methotrexate was the predominant medication (63%), and 56% received at least one immunosuppressive drug plus glucocorticoids. Matched pairs analysis showed that SLE patients with a short disease duration were almost equally burdened by pain, functional limitations and reduced health status as RA patients. After a disease duration of >10 years, however, patients with RA showed poorer outcomes than those with SLE: RA patients reported significantly more often severe pain (30% in RA versus 17% in SLE) and poor global health status (52 versus 38%), and their disease activity as well as severity was rated higher by the rheumatologists. In conclusion, comparing large groups of RA and SLE patients we found a similar burden in early but not in late disease. Taking into account limitations as to the generalizability of the results (recruitment in rheumatologic care, cross-sectional data, underestimation of SLE-specific outcomes), the discrepancy between the high increase in disease-related negative outcomes with longer disease duration in RA but not in SLE indicates a better long-term prognosis in SLE concerning the items observed. The great disparity in treatment intensity between rheumatologists and nonrheumatologists shows that the involvement of a specialist is needed equally in both diseases.
12196041 Anakinra. 2002 Anakinra, a recombinant human interleukin-1 (IL-1) receptor antagonist, is the first biological agent approved to block the pro-inflammatory effects of IL-1 in patients with rheumatoid arthritis. In a double-blind, randomised trial in 472 patients with active, severe or very severe rheumatoid arthritis, recipients of subcutaneous anakinra 150 mg/day achieved higher response rates [assessed using the American College of Rheumatology (ACR) composite score] and accumulated more mean productivity days after 6 months than placebo recipients. However, the response rates and accumulated productivity days of patients receiving subcutaneous anakinra 30 or 75 mg/day for 6 months were similar to those of placebo. With respect to the total Genant radiographic scores, the same study showed that all anakinra treatment regimens slowed disease progression after 6 months to a greater extent than placebo. In double-blind, randomised trials in patients with rheumatoid arthritis, combined treatment with anakinra and methotrexate was associated with higher ACR 20, 50 and 70 response rates than with methotrexate alone. Anakinra, used alone or in combination with methotrexate, was generally well tolerated, with the most frequent adverse event being a mild injection-site reaction of transient duration. Infections requiring antibacterial therapy or hospitalisation occurred more commonly in anakinra recipients than in placebo recipients, but were a rare cause for discontinuation of anakinra therapy (approximately 1%) in clinical trials.
15228618 Effective use of TNF antagonists. 2004 Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.
15228615 Do anti-TNF agents have equal efficacy in patients with rheumatoid arthritis? 2004 Tumor necrosis factor (TNF) antagonists have dramatically improved the outcomes of rheumatoid arthritis (RA). Three agents currently available in the USA--infliximab, etanercept, and adalimumab--have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, and etanercept is a soluble protein. The pharmacokinetic and pharmacodynamic properties of each differs significantly from those of the others. All three agents are effective and safe, and can improve the quality of life in patients with RA. Although no direct comparisons are available, clinical trials provide evidence that can be used to evaluate the comparative efficacy of these agents. Infliximab, in combination with methotrexate, has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, prevent joint erosions and joint-space narrowing, and improve physical function for up to 2 years. Etanercept has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, and slow the rate of joint destruction, and might improve physical function. Etanercept is approved with and without methotrexate for patients who have demonstrated an incomplete response to therapy with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs), as well as for first-line therapy in early RA, psoriatic arthritis, and juvenile RA. Adalimumab relieves the signs and symptoms of RA with and without methotrexate and other DMARDs, decreases total joint score progression, prevents joint erosions and joint-space narrowing in combination with methotrexate, and might improve physical function. When selecting a TNF antagonist, rheumatologists should weigh evidence and experience with specific agents before a decision is made for use in therapy.
15172045 Adalimumab therapy in rheumatoid arthritis. 2004 May Adalimumab is a recombinant human immunoglobulin G1 monoclonal antibody that is specific for human tumor necrosis factor. Based on the data presented in this article, adalimumab administered alone or in patients partially responsive to methotrexate exhibits a rapid onset of action, provides a substantial reduction in signs and symptoms, and results in an improvement in physical function and health-related quality of life. Adalimumab has been demonstrated to inhibit progression of structural joint damage in patients who have long-standing rheumatoid arthritis. Taken together, the data support adalimumab as a new therapeutic option for patients with moderate to severe rheumatoid arthritis.
12087908 [Synchronous programmed intensive therapy of patients with severe rheumatoid arthritis]. 2002 AIM: To evaluate efficiency and safety of intensive treatment program (synchroneous plasmapheresis, large-dose methotrexate and methypred) for patients with severe rheumatoid arthritis (RA). MATERIAL AND METHODS: 45 patients with highly active and progressive RA, systemic symptoms, corticosteroid dependence who had intolerance to standard therapy or had not responded to it were divided into 2 comparable groups. 25 patients of group 1 for a month got 6 plasmapheresis procedures with synchroneous intravenous injection of 40 mg of methotrexate and 250 mg of methypred. 20 patients of group 2 received pulse therapy with methypred (3 g) and methotrexate (200 mg). The intensive therapy was followed in all the patients with methotrexate in a dose 10-20 mg/week. RESULTS: One, six and twelve months after treatment patients of group 1 demonstrated a decrease in RA clinical activity and inflammation. In a year remission by ACR criteria was achieved in one-third of the patients. CONCLUSION: The sychroneous program of intensive therapy is highly effective in RA patients with vasculitis, ineffective standard therapy and corticosteroid dependence.
15170905 Lefunomide in combination therapy. 2004 Jun In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficacious and well tolerated when added to either sulfasalazine or MTX, as both an initial and ongoing treatment for rheumatoid arthritis (RA). Experience in combining leflunomide with biological agents is limited to a small number of open-label studies with infliximab. According to the opinion obtained at an International Expert Panel Meeting held in Paris in May 2003, leflunomide can be used in combination therapy: 61% of the Expert Panel would use leflunomide with MTX, 71% with sulfasalazine, 43% with infliximab, 33% with adalimumab, 19% with etanercept, and 38% with anakinra. The Expert Panel stated that the combination of leflunomide and infliximab warrants a prospective, randomized, controlled trial in patients with incomplete clinical responses to leflunomide monotherapy, provided leflunomide is started first, without a loading dose, and infliximab is added after good tolerability to leflunomide has been established. The Expert Panel concluded that combination therapy with leflunomide has a place in the treatment of RA. Caution is advised, however, when using combination treatments and, therefore, the patient's safety should be carefully monitored.
12404030 [Early electroretinografic changes in elderly RA patients treated with hydroxychloroquine] 2002 Jul OBJECTIVE: To evaluate the effectiveness of fundoscopy, electrooculography, electroretinogram and visually evoked potentials in early detection of hydroxychloroquine retinal toxicity in RA patients and to evaluate the influence of patients' age, drug dosage, concomitant therapy (prednisone and methotrexate) and serum creatinine levels in the development of this side effect. METHODS: From september to december 1999, we have enrolled 32 RA patients (13 males, 19 females) starting hydroxychloroquine treatment. The patients underwent regular ophthalmological examination (fundoscopy, electro-oculography, electroretinogram and visually evoked potentials) every 4 months. Disease activity was evaluated every two months by clinical and routine serological examination. RESULTS: No patients developed retinopathy during 1 year's follow-up; fundoscopy, electrooculography, and visually evoked potentials did not vary from the baseline. On the other hand, electroretinogram showed early alterations of scotopic and photopic response; moreover a significant statistical correlation between patients' age (more than 65 years) and b1 photopic wave increase (p < 0,05) was observed. No correlation was found between the development of electro-retinographic alterations and hydroxychloroquine dosage, concomitant therapy and serum creatinine levels CONCLUSION: Our data show the inefficacy of fundoscopy, electrooculography and visually evoked potentials in early detection of hydroxychloroquine retinopathy. On the other hand electroretinogram allows early detection of retinal alterations during hydroxychloroquine treatment, in patients older than 65 years.
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