Rheumatoid Arthritis: Kremer JM

Kremer JM. · No affiliation provided · Arthritis Rheum. · Pubmed #18975304 No free full text.

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Kremer JM. · No affiliation provided · J Rheumatol. · Pubmed #15170910 links to  free full text

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Kremer JM. · No affiliation provided · J Rheumatol. · Pubmed #12180714 links to  free full text

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Kremer JM. · No affiliation provided · J Rheumatol. · Pubmed #9972951 No free full text.

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Kremer JM, Gibofsky A, Greenberg JD. · Albany Medical College, 1367 Washington Avenue, Albany, NY 12206, USA. · Curr Opin Rheumatol. · Pubmed #18349740 No free full text.

Abstract: PURPOSE OF REVIEW: This review highlights the present state of efforts at registry implementation which exist internationally. These efforts are contrasted with those in the USA. RECENT FINDINGS: The implications of the different data which are derived from diverse registry sources are discussed. The need for long-term data from large and varied sources is fulfilled by registries that collect data from different populations. The potential differences in the nature of the data derived from these registries is dependent upon the national healthcare system from which they are derived, as there are significant differences in access to newer biologic agents which are inconsistent across countries. SUMMARY: Registry data are critical in order to develop an understanding of the performance and safety of new agents in the real world. The challenges for implementing a registry are manifold in the USA because of the somewhat chaotic nature of the healthcare delivery system. In order to overcome these unique challenges, registries in the USA need to be exceptionally well organized and funded, while maintaining independence from the pharmaceutical industry funding sources in the reporting and interpretation of data in peer-reviewed publications. Examples of these registries are provided and discussed.

Kremer JM. · Center for Rheumatology, Albany Medical College, Albany, NY 12206, USA. · Ann Rheum Dis. · Pubmed #16905578 No free full text.

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Kremer JM. · Department of Medicine and Research, The Center for Rheumatology, Albany Medical College, 1367 Washington Avenue, Albany, NY 12206, USA. · J Clin Rheumatol. · Pubmed #16357751 No free full text.

Abstract: T cells have a central role in the orchestration of the immune pathways that contribute to the inflammation and joint destruction characteristic of rheumatoid arthritis (RA). The requirement for a dual signal for T-cell activation and the construction of a fusion protein that prevents engagement of the costimulatory molecules required for this activation has led to a new approach to RA therapy. This approach is mechanistically distinct from other currently used therapies; it targets events early rather than late in the immune cascade, and it results in immunomodulation rather than complete immunosuppression. The fusion protein abatacept is a selective costimulation modulator that avidly binds to the CD80/CD86 ligands on an antigen-presenting cell, resulting in the inability of these ligands to engage the CD28 receptor on the T cell. Abatacept dose-dependently reduces T-cell proliferation, serum concentrations of acute-phase reactants, and other markers of inflammation, including the production of rheumatoid factor by B cells. Recent studies have provided consistent evidence that treatment with abatacept results in a rapid onset of efficacy that is maintained over the course of treatment in patients with inadequate response to methotrexate and anti-tumor necrosis factor therapies. This efficacy includes patient-centered outcomes and radiographic measurement of disease progression. Abatacept has also demonstrated a very favorable safety profile to date. This article reviews the rationale for this therapeutic approach and highlights some of the recent studies that demonstrate the benefits obtained by using abatacept. This clinical experience indicates that abatacept is a significant addition to the therapeutic armamentarium for the management of patients with RA.

Kremer JM. · Albany Medical College, The Center for Rheumatology, Albany, New York 12203, USA. · Autoimmun Rev. · Pubmed #16338211 No free full text.

Abstract: BACKGROUND: Large, long-term databases are needed in order to provide information on the safety and efficacy of new agents used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). These databases can provide data which is well beyond what is available from industry-sponsored investigations. METHODS: The structure, governance, content, context and developmental plan of the CORRONA database are described. RESULTS: The CORRONA database has grown from start up in 2002 to the largest independent database in North America which collects data from both rheumatologists and patients at the time of a clinical encounter. Data are collected as often as every 3 months in RA and every 6 months in PsA. As of the time of this writing, the CORRONA database consists of approximately 9000 patients with RA and 1000 with PsA. Data can be used to elucidate toxicities found in frequencies which would be considerably less common than can be uncovered in industry-sponsored investigations. In addition, actual prescribing patterns and responses in clinical practice can be investigated and described. CONCLUSION: After 3 years of data collection, the CORRONA database is now appropriately able to make significant contributions to our understanding of the safety, efficacy of drugs, as well as demographic, and socioeconomic profiles of patients with RA and PsA. It has evolved from a nascent database to a mature one poised to make significant contributions.

Kalden JR, Antoni C, Alvaro-Gracia JM, Combe B, Emery P, Kremer JM, Strand CV, Van Riel P, Smolen JS. · Medizinische Klinik III, Institute for Clinical Immunology, Erlangen, Germany. · J Rheumatol. · Pubmed #16078347 No free full text.

Abstract: An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective studies were reviewed, principally evaluating combination of leflunomide with infliximab, as well as patient registry data. Available data suggest that combination therapies are more efficacious than monotherapies, reflecting the complementarity of mechanisms of action. Information on side effects remains contradictory, and tolerability of these combinations may vary between different patient groups. In some studies, tolerability is equivalent to that seen with monotherapy; in others a high rate of adverse events has led to frequent treatment discontinuation. Dermatological reactions may be a specific side effect of these combination therapies. Combination therapy is considered justified for treatment of patients diagnosed early who are at risk for rapid progression and for patients who fail to respond to monotherapy. The majority of participants favored adding biological agents to a previously established leflunomide monotherapy rather than starting both treatments simultaneously. On the other hand, combination therapy should be considered with caution in patients with a history of treatment failure, with hepatic comorbidity, or with other autoimmune disease, and in immunocompromised patients. When considering initiation of combination therapy, it is important to provide full information to the patient on the potential benefits and risks of such treatment and to integrate patients as far as possible into the decision-making process.

Kremer JM, Cannon GW. · The Center for Rheumatology, Clinical Professor of Medicine, Albany Medical College, Albany, New York 12206, USA. · Clin Exp Rheumatol. · Pubmed #15552521 No free full text.

Abstract: Leflunomide was first shown to have disease-modifying properties in a rat model of adjuvant-induced arthritis. Leflunomide has been subsequently used with success in several animal models of tissue and organ allograft and of autoimmune disease including collagen- and adjuvant-induced arthritis, interstitial nephritis, myasthenia gravis, and systemic lupus erythematosus. Based on its success as an immunosuppressive agent in these models, leflunomide was tested for the treatment of rheumatoid arthritis (RA).

Kremer JM. · The Center for Rheumatology, 1367 Washington Avenue, Albany, NY 12203, USA. · Rheum Dis Clin North Am. · Pubmed #15172047 No free full text.

Abstract: It is apparent that the potential to significantly affect the immune response exists through artificial modulation of a system of molecules on the surface of T cells that has been designed to specifically provide on-off switches to support or abrogate the activation of T cells. This approach holds considerable promise because it avoids toxicities associated with cell lysis, while theoretically specifically affecting only those T cells, which are being continuously stimulated to become activated. Although there is presently a paucity of studies in humans on the clinical effects of cytotoxic T-lymphocyte antigen 4-immunoglobulin in patients who have rheumatoid arthritis, the existing studies indicate a clear therapeutic value with this approach.

Genovese MC, Kremer JM. · Division of Immunology and Rheumatology, Stanford University Medical Center, 1000 Welch Road, Suite 203, Palo Alto, CA 94304, USA. · Rheum Dis Clin North Am. · Pubmed #15172043 No free full text.

Abstract: Etanercept is effective in the treatment of rheumatoid arthritis (RA)when used as monotherapy and in combination with methotrexate(MTX). Radiographic progression of disease was slowed significantly when the drug was used for a 24-month period and was statistically significantly better than MTX. In addition to its use in RA,etanercept is approved by the U.S. Food and Drug Administration for other rheumatologic conditions, including psoriatic arthritis,ankylosing spondylitis, and juvenile chronic arthritis.

Cannon GW, Kremer JM. · Division of Rheumatology, Department of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA. · Rheum Dis Clin North Am. · Pubmed #15172042 No free full text.

Abstract: Leflunomide is a low-molecular weight, synthetic, oral agent specifically developed for immunosuppression. Because of activity in animal models, leflunomide was tested in rheumatoid arthritis(RA). These investigations have demonstrated that leflunomide reduces the clinical symptoms and signs of RA, improves health related quality of life, and retards structural damage. Leflunomide has been evaluated in RA patients as monotherapy and in combination with methotrexate. Close monitoring for adverse events with particular attention for monitoring liver enzymes for hepatic toxicity is important during treatment with leflunomide.

Stokes DG, Kremer JM. · Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA. · Semin Arthritis Rheum. · Pubmed #12920692 No free full text.

Abstract: OBJECTIVES: To consider the potential of tumor necrosis factor (TNF) neutralization in rheumatologic disorders other than rheumatoid arthritis (RA). METHODS: Literature on the safety and efficacy of TNF inhibition in the treatment of non-RA arthropathies and systemic inflammatory diseases from American and European medical journals was reviewed. RESULTS: Clinical trials, open-label studies, and case studies indicate great promise for TNF inhibitors alone or in combination with other protocols in the treatment of non-RA rheumatologic disorders. In randomized, double-blind, placebo-controlled trials of etanercept and open-label studies of infliximab in patients with psoriatic arthritis, these 2 TNF inhibitors resulted in an approximately 80% to 90% response rate. Double-blind, placebo-controlled, randomized trials also indicate an encouraging degree of efficacy in patients with ankylosing spondylitis. Preliminary evidence from open-label trials and case studies suggests that these TNF inhibitors also may be effective in the treatment of Behçet disease, Wegener granulomatosis, and sarcoidosis. CONCLUSIONS: Neutralization of TNF may have an important role in the treatment of rheumatologic disorders other than RA.

Kremer JM. · Center for Rheumatology, Albany Medical College, Albany, N.Y., USA. · Manag Care. · Pubmed #11729428 No free full text.

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Wolfe F, Cush JJ, O'Dell JR, Kavanaugh A, Kremer JM, Lane NE, Moreland LW, Paulus HE, Pincus T, Russell AS, Wilskie KR. · National Data Bank for Rheumatic Diseases-Arthritis Research Center Foundation, Inc. and University of Kansas School of Medicine, Wichita, Kansas, USA. · J Rheumatol. · Pubmed #11409141 No free full text.

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Kremer JM. · The Center for Rheumatology, Albany, New York, USA. · Ann Intern Med. · Pubmed #11304108 links to  free full text

Abstract: Because of radiographic evidence of progressive bone loss and the inability to eliminate synovial proliferation with methotrexate, it became apparent that therapy for rheumatoid arthritis needed further advancement. Methotrexate is not a remission-inducing drug and may have dose-limiting toxicity. In the past 2 years, three new disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab. Each of these agents has demonstrated efficacy compared with placebo in randomized, controlled studies. Because methotrexate had a dominant therapeutic role, the new drugs were also studied in combination with it. Other established DMARDs, such as sulfasalazine and hydroxychloroquine, have also demonstrated efficacy when used together with methotrexate. The results of these combination studies clearly demonstrate that clinical responses can be meaningfully improved when new and existing DMARDs are added to methotrexate. Although toxicity remains a serious concern when powerful immune modulators and antimetabolites are used in combination, relatively few serious adverse events have been reported during 2-year treatment periods. It has also become apparent that combinations of new DMARDs and methotrexate virtually halt radiographic progression over 2 years. The new agents are expensive, but annual costs must be weighed against the personal and societal expense of joint arthroplasty, hospitalizations, disability, and diminished quality of life that accompanies poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD therapy with methotrexate will be determined by long-term data on safety, efficacy, and effects on radiographic deterioration of bone. Additional long-term observational data on the incidence of joint arthroplasty and disability will help to place the issue of societal costs in a better perspective. This will allow the value of aggressive treatment to be established with certainty.

Kremer JM. · Division of Rheumatology, Albany Medical College, New York 12208, USA. · Am J Clin Nutr. · Pubmed #10617995 links to  free full text

Abstract: Ingestion of dietary supplements of n-3 fatty acids has been consistently shown to reduce both the number of tender joints on physical examination and the amount of morning stiffness in patients with rheumatoid arthritis. In these cases, supplements were consumed daily in addition to background medications and the clinical benefits of the n-3 fatty acids were not apparent until they were consumed for > or =12 wk. It appears that a minimum daily dose of 3 g eicosapentaenoic and docosahexaenoic acids is necessary to derive the expected benefits. These doses of n-3 fatty acids are associated with significant reductions in the release of leukotriene B(4) from stimulated neutrophils and of interleukin 1 from monocytes. Both of these mediators of inflammation are thought to contribute to the inflammatory events that occur in the rheumatoid arthritis disease process. Several investigators have reported that rheumatoid arthritis patients consuming n-3 dietary supplements were able to lower or discontinue their background doses of nonsteroidal antiinflammatory drugs or disease-modifying antirheumatic drugs. Because the methods used to determine whether patients taking n-3 supplements can discontinue taking these agents are variable, confirmatory and definitive studies are needed to settle this issue. n-3 Fatty acids have virtually no reported serious toxicity in the dose range used in rheumatoid arthritis and are generally very well tolerated.

Kremer JM. · Department of Medicine, Albany Medical College, New York 12208-3479, USA. · Clin Exp Rheumatol. · Pubmed #10589356 No free full text.

Abstract: More publications in the medical literature have described the clinical efficacy and toxicity of methotrexate (MTX) than of any other drug ever used for rheumatic diseases. A knowledgeable clinical can thus rely on evidence-based medicine to guide the use of this agent. Because MTX is not remission-inducing, many new therapies are being combined with it in order to achieve a greater therapeutic response. This trend will likely continue and expand as more novel agents are introduced.

Pincus T, O'Dell JR, Kremer JM. · Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Ann Intern Med. · Pubmed #10577301 links to  free full text

Abstract: The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.

Kremer JM. · Department of Medicine, The Albany Medical College, NY 12208-3479, USA. · Semin Arthritis Rheum. · Pubmed #10468411 No free full text.

Abstract: OBJECTIVES: Methotrexate is currently one of the most widely prescribed disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA). Combination therapy of methotrexate with other DMARDs increases the clinical success of low-dose methotrexate treatment. Leflunomide is a new DMARD that may have a high potential for success in combination therapy with methotrexate. This review compares the mode of action of methotrexate and leflunomide and speculates on how this contributes to therapeutic efficacy in RA when these agents are used singly or in combination. METHODS: A literature review of the biochemical mechanisms considered to be the basis for the therapeutic efficacy of methotrexate and leflunomide in treating RA is presented. RESULTS: Low-dose methotrexate inhibits cytokine production, purine biosynthesis, and, in an animal model, causes the release of adenosine, a potent antiinflammatory agent. Leflunomide, through inhibition of de novo pyrimidine biosynthesis, can regulate lymphocyte proliferation. CONCLUSIONS: The biochemical mechanisms underlying the therapeutic efficacy of low-dose methotrexate and leflunomide in the treatment of RA are quite different. The potentially complementary mechanisms of action of these two effective DMARDs should provide a rationale for their use in combination therapy for patients whose condition no longer responds to methotrexate alone.

Westhovens R, Kremer JM, Moreland LW, Emery P, Russell AS, Li T, Aranda R, Becker JC, Qi K, Dougados M. · Department of Rheumatology, KU Leuven, Herestraat 49, B 3000 Leuven, Belgium. · J Rheumatol. · Pubmed #19273451 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis. METHODS: Patients were randomized to abatacept 10 or 2 mg/kg or placebo, plus MTX. Patients completing the 1-year, double-blind period entered the longterm extension, where all patients received a fixed dose of abatacept ~10 mg/kg. We describe safety analyses for all patients who received at least 1 dose of abatacept and efficacy analyses for the original ~10 mg/kg abatacept-treated group, over 5 years. RESULTS: Of the 235 abatacept- or placebo-treated patients completing the double-blind period, 219 entered the longterm extension; 130 (59.4%) were continuing at Year 5. No unexpected safety events were observed during the longterm extension compared with the double-blind period. Incidence rates of adverse events (AE) and serious AE were 489.7 and 20.0/100 patient-years in Year 1 versus 374.9 and 18.9/100 patient-years in the cumulative period, respectively. Using exploratory analyses, improvements observed at Year 1 in the 10 mg/kg group were maintained at Year 5, as assessed by ACR responses (ACR20=77.1% vs 82.7%; ACR50=53.0% vs 65.4%; ACR70=28.9% vs 40.4% at Years 1 and 5, respectively) and disease activity (Low Disease Activity State=48.2% vs 58.5%; Disease Activity Score-28-defined remission=25.3% vs 45.3% at Years 1 and 5, respectively). CONCLUSION: Abatacept maintained the efficacy observed at Year 1 over 5 years of treatment, and demonstrated consistent safety and tolerability. These data, along with relatively high retention rates, support the longterm clinical benefit provided by selective T cell costimulation modulation. Clinical trial registry: ClinicalTrials.gov; clinical trial registration number: NCT00254293.

Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechiński J, Li T, Teng J, Becker JC, Westhovens R. · Center for Rheumatology, Albany Medical College, Albany, New York 12206, USA. · Arthritis Rheum. · Pubmed #18383390 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy, radiographic changes, and safety of abatacept and methotrexate therapy through 2 years in a long-term extension of a previously published 1-year study. METHODS: Patients who received placebo during year 1 were switched to abatacept. Patients taking abatacept continued to take it. Efficacy and safety were assessed through 2 years. RESULTS: Of 539 patients enrolled in the initial 1-year study, 488 completed 1 year of the long-term extension (2% discontinued for lack of efficacy). At 2 years, patients taking abatacept had maintained their responses on the American College of Rheumatology (ACR) improvement criteria and the Disease Activity Score in 28 joints (DAS28; using the C-reactive protein [CRP] level), as well as their physical function (according to the Health Assessment Questionnaire [HAQ] disability index [DI]) and health-related quality of life (HRQOL; assessed with the Short Form 36 [SF-36] health survey), that were observed at the end of the double-blind period (year 1 versus year 2 values were 81.9% versus 80.3% for ACR 20% improvement, 25.4% versus 30.9% for a DAS28 [CRP] of <2.6, 71.8% versus 66.8% for the HAQ DI, and 9.7 versus 10.6 and 7.3 versus 7.2, respectively, for the mean change in the physical and mental components summary scores of the SF-36). In the abatacept group, post hoc analysis demonstrated further inhibition of radiographic progression during year 2 (57% reduction in mean change of total score in year 2 versus year 1; P<0.0001), and minimal radiographic progression was observed (mean change in total score from baseline was 1.1 and 1.6 at year 1 and 2, respectively). Rates of adverse events (AEs) and severe AEs were consistent throughout the cumulative period. CONCLUSION: The improvements in signs and symptoms, physical function, and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of treatment. This durability was accompanied by a safety profile consistent with that in the double-blind portion of the study. Radiographic progression was further inhibited in year 2 compared with year 1, suggesting an increasing effect of abatacept on the inhibition of structural damage in year 2.

Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R. · Center for Rheumatology, Albany, New York, USA. · Ann Intern Med. · Pubmed #16785475 links to  free full text

Abstract: BACKGROUND: The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies. OBJECTIVE: To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment. DESIGN: One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004). SETTING: 116 centers worldwide. PATIENTS: 652 patients with active rheumatoid arthritis despite methotrexate treatment. INTERVENTION: Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo. MEASUREMENTS: Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year. RESULTS: Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients. LIMITATIONS: The study involved only 1 group of patients over 1 year. CONCLUSIONS: Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.

Fleischmann RM, Cohen SB, Moreland LW, Schiff M, Mease PJ, Smith DB, Keenan G, Kremer JM, Anonymous00083. · Radiant Research--Dallas, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75235, USA. · Curr Med Res Opin. · Pubmed #16083527 No free full text.

Abstract: OBJECTIVE: Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered. METHODS: Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure. RESULTS: Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54. CONCLUSION: Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.