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      Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study

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          Abstract

          The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9–3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.

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          Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial.

          To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor alpha antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX. In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks. An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events. The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
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            Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria.

            To determine which cut-off point in the RA disease activity score (DAS28) corresponds to fulfilment of the ARA criteria for clinical remission. The disease activity of patients included in the Nijmegen RA inception cohort was systematically assessed every 3 months. For all visits, a modification of the ARA preliminary criteria for clinical remission was applied and the DAS28 was calculated. Receiver operating characteristic analysis was used to determine the cut-off point with maximum sensitivity and specificity in DAS28 corresponding with fulfilment of the modified ARA criteria. Three hundred and seventy-eight patients contributed 4378 visits. In 6.5% of the visits four of the five items and in 1.5% all five items of the modified ARA criteria were fulfilled. The optimal cut-off point for the DAS28 that corresponds to fulfilment of the modified ARA criteria was determined to be 2.66. DAS28 <2.6 corresponds to fulfilment of the preliminary ARA criteria for clinical remission in RA.
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              Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials.

              Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials. Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria. Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status. RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.
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                Author and article information

                Contributors
                +49-931-201-40100 , +49-931-201-640100 , Kleinert_S@klinik.uni-wuerzburg.de
                Journal
                Rheumatol Int
                Rheumatol. Int
                Rheumatology International
                Springer-Verlag (Berlin/Heidelberg )
                0172-8172
                1437-160X
                6 August 2011
                6 August 2011
                September 2012
                : 32
                : 9
                : 2759-2767
                Affiliations
                [1 ]Rheumatologie/Klinische Immunologie, Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Oberdürrbacherstr. 6, 97080 Würzburg, Germany
                [2 ]Rheumatology Clinic, Immanuel Hospital, Berlin, Germany
                [3 ]Ratingen Clinic, Ratingen, Germany
                [4 ]Rheumatology Medical Center, Stuttgart, Germany
                [5 ]Rheumatology Medical Center, Villingen-Schwenningen, Germany
                [6 ]Rheumatology Medical Center, Zerbst, Germany
                [7 ]GKM Gesellschaft für Therapieforschung, Munich, Germany
                [8 ]Abbott GmbH & Co. KG, Wiesbaden, Germany
                Article
                2033
                10.1007/s00296-011-2033-5
                3429775
                21822659
                823fa76b-66a5-495e-949b-59bf158bc523
                © The Author(s) 2011
                History
                : 8 February 2011
                : 10 July 2011
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2012

                Rheumatology
                arthritis, rheumatoid,adalimumab,antirheumatic agents,regression analysis,treatment outcome

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