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ID PMID Title PublicationDate abstract
12583612 Anti-TNFalpha therapy for rheumatoid arthritis: an update. 2003 Jan Many studies have confirmed that the long term use of biological agents targeting TNFalpha in therapy for rheumatoid arthritis give rise to sustained improvement in symptoms and signs of disease provided the anti-TNF agent is efficacious and of low immunogenicity. The current regimes for infliximab 3 or 10 mg/kg infusion in combination with weekly oral methotrexate, or of subcutaneous etanercept 25 mg twice per week fulfil these criteria. D2E7, a 'human' antibody produced by phage display, has also demonstrated efficacy in clinical trials. It has recently emerged that anti-TNF therapy protects joints from structural damage. One year data for infliximab and methotrexate combination therapy suggest that this regime reduces disability. In early RA, etanercept acts more rapidly than methotrexate to decrease symptoms and retard progression of erosions. In conclusion, for patients with established and early RA, anti-TNF therapies set a new standard for symptom control and joint protection.
12522841 Cost effectiveness of adding leflunomide to a 5-year strategy of conventional disease-modi 2002 Dec 15 OBJECTIVE: To estimate, from a public payer's perspective, the 5-year cost effectiveness of adding leflunomide (LEF) to a sequence of disease-modifying antirheumatic drugs (DMARDs) representative of a typical rheumatoid arthritis (RA) management approach adopted by Canadian rheumatologists. METHODS: A DMARD sequence including LEF was compared with one excluding it, using a 5-year simulation model where patients with RA cycle through different treatment regimens. Data were obtained through a systematic literature search (drug withdrawal rates, number and type of adverse events, American College of Rheumatology 20% responder status) and separately conducted surveys (choice of DMARD sequence, management of adverse events). Costs for adverse event management were calculated using the Ontario Schedule of Benefits, and monitoring costs were calculated according to official Canadian product monograph recommendations. Wholesale prices of all drugs were adjusted by the allowable markup and prescription fees. Utilities (as measured by the standard gamble [SG] and rating scale [RS] techniques) were obtained from 482 patients who participated in a 1-year randomized controlled trial that compared LEF, methotrexate, and placebo. Costs and utilities were discounted by 3%. Probabilistic sensitivity analysis was performed. RESULTS: Adding LEF to a conventional strategy of DMARDs increased the 5-year management costs by $1,231 compared with the strategy without LEF, which results in a cost-effectiveness ratio of $13,096 per additional year of response to treatment, and cost-utility ratios of $54,229 (RS) and $71,988 (SG) per quality-adjusted life-year gained. CONCLUSION: Adding LEF as a new option to a conventional sequence of DMARDs extends the time patients may benefit from DMARD therapy at a reasonable cost effectiveness and cost utility. LEF data are limited to clinical trials; data from observational studies would be needed to corroborate these findings.
15103244 Perioperative management of patients with rheumatoid arthritis in the era of biologic resp 2004 May PURPOSE OF REVIEW: This article provides guidelines for the perioperative management of the most commonly used antirheumatic drugs being used to treat patients with rheumatoid arthritis, with an emphasis on the relatively new addition of biologic response modifiers. RECENT FINDINGS: Few clinical data exist examining the perioperative management of the biologic drugs, which include the inhibitors of tumor necrosis factor-alpha (etanercept, infliximab, and adalimumab), the interleukin-1 receptor antagonist anakinra, and to a much lesser extent the CD20 inhibitor rituximab. The only human data available in that regard is based on the use of the tumor necrosis factor-alpha inhibitor infliximab in surgical patients with Crohn disease. Although quite limited, that data appeared favorable in finding that infliximab did not result in an increased risk of postoperative complications in that setting. SUMMARY: Perioperative guidelines have never been well established for a majority of the traditional antirheumatic drugs in use today. Recommendations for the perioperative use of nonsteroidal antiinflammatory drugs and glucocorticoids have the most evidence-based support. Data for the use of methotrexate are also available from which to generate reasonable guidelines; however, for the remaining antirheumatic drugs in current use, the available data cannot support any clear evidence-based recommendations. To provide reasonable guidelines for the use of the biologics, perhaps the best we can do is to extrapolate from the very limited data coming from the concurrent use of infliximab in patients with Crohn disease who have undergone surgery. Beyond that, we are left with animal and tissue culture data from which any recommendations would be rather tenuous.
11840438 Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid art 2002 Feb OBJECTIVE: Ethical constraints on the conduct of placebo-controlled trials evaluating new therapies for serious chronic diseases, such as rheumatoid arthritis (RA), indicate the need for discerning methods to assess treatment effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic resonance imaging (DEMRI) is a sensitive technique for the detection of synovial inflammation in RA. Therefore, this investigation was undertaken to evaluate DEMRI as an efficacy assessment tool for differentiating treatment effect in a randomized, active-controlled trial comparing leflunomide and methotrexate. METHODS: Patients with active RA (n = 39) were randomized in a 2-center, prospective, double-blind clinical trial to receive either leflunomide (n = 18) or methotrexate (n = 21) therapy for 4 months. DEMRI scans were obtained at baseline and at 4 months, and the initial rate of enhancement (IRE) and the maximal signal intensity (SI) enhancement (ME) were calculated from the SI curves. Clinical improvement was assessed by conventional outcome measures. RESULTS: Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baseline and end point DEMRI scans. Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05). Average values of ME indicated reduction of inflammation with both leflunomide and methotrexate. The improvement in clinical signs and symptoms, as measured by traditional assessments, was comparable for both active treatments. CONCLUSION: Results of this study validate the sensitivity of DEMRI in detecting inflammatory changes in active RA in response to treatment. Improvement in synovial inflammation as measured by IRE was significantly better with leflunomide than with methotrexate over 4 months of therapy.
14513118 [Idiopathic hypereosinophilic syndrome associated with rheumatoid arthritis. A case report 2003 The idiopathic hypereosinophilic sindrome (HES) is a disease characterized by persistent blood eosinophilia (> 1500 eosinophils/mm3 > 6 months) -in absence of other ethiologies for eosinophilia (parasitic, allergic, immunological or malignant diseases)- associated with multiple organ involvement (heart, lung, central nervous system, skin, bone marrow, gastrointestinal tract). Reports on rheumatologic manifestations in patients with HES are very rare. In the case we report a typical rheumatoid arthritis developed in a 58-year-old woman with HES treated with glucocorticoids. Because of the marked glucocorticoids side effects shown by the patient (cushingoid habitus, hyperglycemia), we stopped this treatment and replaced it at first by methotrexate and later by cyclosporin, both of them associated with sulfasalazine. These drugs revealed very efficacious both on articular pathology and on the clinical and laboratory manifestations of HES. These data suggest that common pathogenetic mechanisms are likely acting in rheumatoid arthritis and idiopathic hypereosinophilic syndrome.
15526004 Genetic risk factors for infection in patients with early rheumatoid arthritis. 2004 Dec We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis (RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): (TNF -308, -238, and + 488); lymphotoxin-alpha (LTA) (LTA + 249, + 365, and + 720); and Fc gamma receptors FCGR2A 131 H/R; FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P = 0.038). Urinary tract infection (UTI) was associated with the TNF -238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05-6.25) and LTA +365 C (OR 1.73, 95% CI 1.07-2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99-3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (P < 0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.
12120905 Methotrexate twice weekly vs once weekly in rheumatoid arthritis: a pilot double-blind, co 2002 May Methotrexate (MTX) is the most commonly used disease-modifying antirheumatoid drug used in patients with rheumatoid arthritis. It is usually given on a weekly schedule, but as the half-life of its active compound, the polyglutamate MTX, is 3 days, we did a pilot study to see if MTX twice weekly is superior to MTX once weekly. Eighty patients with rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) criteria were enrolled into a double-blind, controlled trial of 16-week duration. Patients achieving ACR scores of 20 and 50 were determined at 8 and 16 weeks. In addition, the incidence of hepatotoxicity was also studied. Of the 80 patients, 66 completed 8 weeks of study, whereas 53 completed 16 weeks of study. Most withdrawals were because of inefficacy. At 8 weeks, ACR 20 response (24/34 in once weekly and 22/32 in twice weekly) and ACR 50 response (16/34 in once weekly and 16/32 in twice weekly) in both groups were similar. Even at 16 weeks, there was no significant difference in ACR 20 and ACR 50 responses. Intent-to-treat analysis also yielded similar results. Five patients in each group had a mild reversible rise in transaminases. Our study suggests that MTX twice weekly has no advantage over once weekly regarding efficacy, and thus the currently used once weekly regimen is good enough till alternate dosing schedules are evaluated in a large multicentric trial.
15194591 Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast inv 2004 Jul OBJECTIVE: To investigate the effect of methotrexate (MTX) and albumin coupled with methotrexate (MTX-HSA) on cartilage invasion and induction of perichondrocytic degradation by rheumatoid arthritis synovial fibroblasts (RA SF) in vivo. METHODS: Human cartilage and RA SF were co-transplanted in three groups of severe combined immunodeficient mice (SCID), which received 1 mg/kg free MTX (n = 9), 1 mg/kg MTX-HSA (n = 6), or 0.9% NaCl (n = 5), respectively, intraperitoneally twice a week. After 4 weeks' treatment, the mice were killed and the implants analysed histologically. RESULTS: The control group had a mean (SEM) score for cartilage invasion of RA SF of 2.0 (0.26) and for perichondrocytic cartilage degradation of 1.5 (0.34). In contrast, mice which received MTX showed a significantly reduced invasion (0.78 (0.14), p<0.01) and a reduction in perichondrocytic cartilage degradation scores (0.69 (0.2), p<0.05) in comparison with the control group. Mice treated with MTX-HSA also had significantly reduced scores for RA SF invasion into the cartilage (0.92 (0.41), p<0.05) and for cartilage degradation (0.83 (0.44), p<0.05) compared with controls. The effects of MTX and MTX-HSA were not significantly different between these two groups. CONCLUSION: Treatment with MTX or MTX-HSA significantly ameliorates cartilage destruction in the SCID mouse model for human RA.
14722200 Acquired resistance of human T cells to sulfasalazine: stability of the resistant phenotyp 2004 Feb BACKGROUND: A recent study from our laboratory showed that induction of the multidrug resistance related drug efflux pump ABCG2 contributed to acquired resistance of human T cells to the disease modifying antirheumatic drug (DMARD) sulfasalazine (SSZ). OBJECTIVES: To investigate the duration of SSZ resistance and ABCG2 expression after withdrawal of SSZ and rechallenging with SSZ, and to assess the impact of SSZ resistance on responsiveness to other DMARDs. METHODS: Human CEM cells (T cell origin) with acquired resistance to SSZ (CEM/SSZ) were characterised for (a) SSZ sensitivity and ABCG2 expression during withdrawal and rechallenge of SSZ, and (b) antiproliferative efficacy of other DMARDs. RESULTS: ABCG2 protein expression was stable for at least 4 weeks when CEM/SSZ cells were grown in the absence of SSZ, but gradually declined, along with SSZ resistance levels, to non-detectable levels after withdrawal of SSZ for 6 months. Rechallenging with SSZ led to a rapid (<2.5 weeks) resumption of SSZ resistance and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8-fold), were moderately more sensitive (1.6-2.0 fold) to cyclosporin A and chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid dexamethasone as compared with parental CEM cells. CONCLUSION: The drug efflux pump ABCG2 has a major role in conferring resistance to SSZ. The collateral sensitivity of SSZ resistant cells for some other (non-related) DMARDs may provide a further rationale for sequential mono- or combination therapies with distinct DMARDs upon decreased efficacy of SSZ.
11899752 Treating rheumatoid arthritis with new disease modifying drugs. 2002 Rheumatoid arthritis (RA) is a serious illness that can only be controlled by the appropriate use of disease modifying anti-rheumatic drugs (DMARDs). In spite of the successful use of such substances, and of methotrexate in particular, a large number of patients still experience disease progression. Leflunomide and the two anti-TNF agents, infliximab and etanercept, were therefore warmly greeted as very welcome additions to the rheumatologist's armamentarium. These successful newcomers, their strengths and problems are the focus of the present review.
12510357 [Usefulness of serum matrix metalloproteinase-3(MMP-3) level in the diagnosis of rheumatoi 2002 Dec Matrix metalloproteinase-3 is abundantly expressed in active rheumatoid synovium, and serum level of MMP-3 is a useful marker not only for the diagnosis of rheumatoid arthritis but also for the evaluation of prognosis in the joint destruction. It should be noted, however, that serum MMP-3 may be increased in other inflammatory arthritis, thus its specificity for the diagnosis of early RA may not be high enough. Recent reports indicated that methotrexate or anti-TNF alpha therapy effectively suppressed the serum MMP-3 level during the course of the treatment, whereas corticosteroid didn't. Thus, suppression of serum MMP-3 could explain the discrepancy in the inhibition of bony destruction in RA patients by the therapeutic strategy.
12610799 Allele and antigen-specific treatment of rheumatoid arthritis: a double blind, placebo con 2003 Mar OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.
12810924 Radiographic progression in early rheumatoid arthritis: a 12-month randomized controlled s 2003 Dec OBJECTIVE: To determine whether patients with early rheumatoid arthritis (RA) treated with cyclosporin A (CsA) and methotrexate (MTX) in combination for 12 months show a lower rate of radiographic deterioration than those treated with MTX alone. METHODS: In this controlled and randomized single-blind trial, 61 consecutive patients with untreated RA of less than 2 yr duration were treated with either CsA + MTX combination therapy (n = 30) or MTX alone (n = 31). The primary end-point was radiographic progression after 12 months, measured using the damage score (DS) of the Sharp and van der Heijde method. RESULTS: Although there was a significant difference between the mean baseline and 12-month DS in both treatment groups (MTX/CsA, 1.93 +/- 0.90; MTX, 7.47 +/- 2.03), it was significantly less in the combination arm (P = 0.018). Of the 30 evaluable CsA + MTX patients, 16 (53%) were ACR20 responders, 15 (50%) ACR50 and 14 (47%) ACR70; the corresponding figures in the MTX arm were 19 (61%), 13 (44%) and 6 (19%). Toxicity was acceptable in both groups. CONCLUSIONS: In patients with early RA, CsA + MTX combination therapy led to a significantly lower rate of 12-month radiographic progression, was effective on inflammatory articular symptoms, and was well tolerated.
14989427 Anakinra as a new therapeutic option in rheumatoid arthritis: clinical results and perspec 2002 Sep Interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 gene family, which blocks IL-1-mediated signal transduction. In rheumatoid arthritis (RA), recombinant human IL-1Ra (anakinra) has been evaluated in 5 randomized, placebo-controlled clinical trials. In the European monotherapy study, 43% of patients receiving 150 mg/day anakinra achieved a 20% response according to the American College of Rheumatology criteria (ACR 20), compared to 27% in the placebo group. In the methotrexate combination therapy study, 42% of the patients receiving 1 mg/kg/day anakinra achieved an ACR20 response, 24% an ACR50 response, and 10% an ACR70 response. In each study, clinically meaningful improvements in the Health Assessment Questionnaire scores were observed. The Economic Resource Survey was employed in the European monotherapy study to evaluate patient and caregiver days of missed work or domestic activity in successive 4-week periods. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose-related. The mean change in the total modified Sharp score of patients who completed treatment with anakinra was significantly less than in the patients who received placebo. Anakinra, a new biologic approach to the treatment of RA, results in significant improvements in the signs and symptoms, has beneficial effects on functional status, and on the rate of progressive structural joint damage.
12096222 Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral 2002 Jul OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.
12920694 Effectiveness of psoriatic arthritis therapies. 2003 Aug OBJECTIVE: To review the effectiveness of systemic therapies for psoriatic arthritis (PsA). METHODS: Data on the efficacy of PsA therapies from selected literature, including American and international medical journals and recent abstracts from key rheumatology meetings, were reviewed. RESULTS: Most therapeutic agents used to treat PsA are used on the basis of data from patients with rheumatoid arthritis (RA), and have not been adequately assessed in patients with PsA. However, the progressively destructive nature of the disease demands aggressive treatment with agents tested specifically in PsA. Conventional agents used to treat RA, such as methotrexate and sulfasalazine, have adverse effects that often lead to drug discontinuation and may not always be effective in reducing symptoms or radiographic progression in PsA. Newer medications, such as etanercept and infliximab, specifically inhibit the actions of tumor necrosis factor, which plays a major role in joint destruction. The Food and Drug Administration has recently approved etanercept for treatment of PsA. Current data with infliximab are limited to small open-label trials; however, randomized controlled trials are underway. CONCLUSIONS: PsA and RA are distinct diseases, and the efficacy and safety of an agent in RA cannot necessarily be equated with efficacy and safety in PsA. For most conventional agents, data from controlled clinical trials in PsA are scant. Etanercept is currently the only therapeutic agent with sufficient data from placebo-controlled, randomized trials to receive a Food and Drug Administration indication for the treatment of PsA.
12491140 [Essential cryoglobulinemic vasculitis with severe peripheral neuropathy and neurogenic mu 2002 Dec We report on a 60 year old patient with peripheral neuropathy, neurogenic muscular atrophy, skin ulcers, arthritis and weakness. Detection of cryoglobulins in association with typical clinical symptoms, exclusion of hepatitis C and any other disease led to a rare diagnosis: essential cryoglobulinemic vasculitis. The case demonstrates not only the difficult diagnostic process but also the problems of an adequate and effective therapy. Since the usual immunosuppressive treatments such as methotrexate, high dose corticosteroid and intermittent intravenous pulse cyclophosphamide therapy (Austin's scheme) failed, we performed plasmapheresis (cascade filtration), which brought about an immediate and long-term remission. Besides discussing various types of plasmapheresis procedures and potential pathophysiological mechanisms, we point out that this therapy could find an early use in severe essential cryoglobulinemic vasculitis because of its excellent risk/benefit ratio.
15077287 Sustained improvement over two years in physical function, structural damage, and signs an 2004 Apr OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). RESULTS: The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. CONCLUSION: Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.
14657509 The impact of escalating conventional therapy in rheumatoid arthritis patients referred fo 2004 Mar OBJECTIVE: To assess the impact of escalating conventional therapy in patients with RA who satisfy BSR/NICE criteria for biologics. METHODS: A total of 308 consecutive patients referred to a tertiary centre for biological therapy between January 1999 and February 2001 were studied prospectively. They were considered by their own consultant to have failed standard therapy. Prior to biologics, conventional therapy was escalated to include combination and parenteral methotrexate treatment. Patients were assessed at 12-weekly intervals for 1 yr and therapy was changed if response was not satisfactory. The subsequently released BSR/NICE biologic eligibility criteria were applied retrospectively. Response (disease activity, disability and quality of life) to escalated therapy in those patients who did or did not satisfy current eligibility criteria were compared. RESULTS: In total, 159 satisfied BSR/NICE criteria and would have been eligible for immediate treatment with biologics [DAS28 > 5.1, failed methotrexate (20 mg/week or lower dose owing to toxicity) and one other DMARD]; however, 93 of these responded to escalated conventional therapy and did not require biologics [significant improvement (P < 0.01) in disease activity, disability and quality of life]. However, mild disease activity (DAS28 < 3.2) was only achieved in 7% of these patients at 12 months. CONCLUSIONS: Although over half the patients who satisfied standard criteria for biologics responded satisfactorily to escalated therapy, only a minority achieved mild disease activity. The savings achieved by treating with conventional therapies need to be weighed against the risk of persistent disease activity.
14969070 The Utrecht experience with different treatment strategies in early rheumatoid arthritis. 2003 Sep Since 1990 the Utrecht Rheumatoid Arthritis Cohort study group has performed several clinical trials on different treatment strategies in early rheumatoid arthritis (RA) patients. From 1990 till 1994, patients were randomly assigned to the pyramid strategy group or the early DMARD group. Patients in the early DMARD group were allocated to one of the three following treatment strategies: strategy I, starting with hydroxychloroquine (HCQ); strategy II, starting with intramuscular gold (iAU); or strategy III, starting with oral methotrexate (MTX). After one year, statistically significant advantages for the early DMARD group compared with the pyramid group were found for disability, pain, joint score, and ESR. The increase in radiological damage did not differ significantly between the two strategy groups. These first year results proved that early introduction of DMARDs is more beneficial than a delayed introduction. After 5 years, however, no prolongation of the clinical advantages in favor of the early DMARD group, as observed after one year, was found. It was found that patients assigned to the pyramid group received more intra-articular injections during the first two years; at the end of this period 75% of them used DMARDs, especially the more aggressive DMARDs. Based on the first year results, all patients were randomly assigned to one of the three treatment strategies in the early DMARD group between 1994 and 1998. Patients who started with MTX or iAU as the first DMARD demonstrated better results regarding clinical efficacy and radiological damage after 2 years. However, more patients who received iAU therapy had to discontinue their therapy compared with patients who took MTX. We therefore conclude that MTX is the DMARD of first choice and that treatment should be tailored to the individual patient.
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