Ronald Pedersen

Wiener Krankenanstaltenverbund, Wien, Vienna, Austria

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Publications (19)237.84 Total impact

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    ABSTRACT: We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy.
    New England Journal of Medicine 11/2014; 371(19):1781-92. · 54.42 Impact Factor
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    ABSTRACT: Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials.
    Annals of the rheumatic diseases. 08/2014;
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    ABSTRACT: Previous global studies examined etanercept (ETN) + methotrexate (MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from Latin America. The objective of this study was to compare the safety and efficacy of ETN + MTX versus a standard-of-care disease-modifying antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy. This open-label, active-comparator study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281; DMARD + MTX, n = 142). The primary end point was the proportion achieving American College of Rheumatology (ACR) 50 at week 24. Secondary end points included ACR20/70, disease activity score (DAS) 28 measures, and mean change in modified total Sharp score. Patient-reported outcomes were the Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and Resource Utilization. Statistical analyses were stratified by country; χ test and analysis of covariance were used. Adverse events were monitored. More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs 23%, respectively), in addition to secondary end points (P < 0.0001 for all); mean change in modified total Sharp score was lower for the ETN + MTX group (0.4 vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver Burden and Resource Utilization emergency department visits for RA (P < 0.01). Overall, adverse events were similar between the groups (69% vs 68%,); serious adverse events were also similar (4% vs 1%). The rate of overall infections was higher with ETN + MTX (38%) than DMARD + MTX (22%, P ≤ 0.001). Consistent with published global data among RA patients with inadequate response to MTX, adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided favorable benefit-risk profile among RA patients from LA region.
    Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 12/2013; · 1.19 Impact Factor
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    ABSTRACT: Abstract Objective: To assess cardiometabolic biomarkers in patients with psoriasis before and after etanercept treatment. Methods: Patients with moderate-to-severe plaque psoriasis were randomized to etanercept 50 mg once or twice weekly, double-blinded. Cardiometabolic biomarkers were assessed at baseline and after 12 weeks of treatment (n = 273). Results: At baseline, 42% of patients had metabolic syndrome. Etanercept was not associated with any clinically relevant adverse effects on cardiometabolic biomarkers. In the once-weekly subgroup, significant mean percentage changes from baseline (p < 0.05) were observed for the quantitative insulin-sensitivity check index (QUICKI; -2.2%), apolipoprotein (Apo) A1 (3.2%), Apo B:Apo A1 ratio (-3.5%), leptin (8.6%) and high-sensitivity C-reactive protein (hsCRP) (-65.5%); and in the twice-weekly subgroup for plasma insulin (15.9%), QUICKI (-2.7%), high-density lipoprotein cholesterol (HDL-C; 2.9%), apolipoprotein (Apo) A1 (2.8%), Apo B:Apo A1 (-4.6%) and hsCRP (-74.4%). Conclusion: Metabolic syndrome was common in these patients with moderate-to-severe psoriasis. Etanercept treatment may provide some potentially favorable modulation of insulin sensitivity, HDL-C, Apo A1 and Apo B:Apo A1 ratio.
    Journal of Dermatological Treatment 11/2013; · 1.50 Impact Factor
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    ABSTRACT: Confirmatory factor analysis (CFA) of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) three-factor posttraumatic stress disorder (PTSD) diagnostic criteria was conducted to determine fit for this patient population. An exploratory factor analysis (EFA) of alternate symptom structures was planned to identify symptoms that cluster in this population. The response of symptom factors to treatment with venlafaxine extended release (ER) was explored. Baseline 17-item Clinician-Administered PTSD Scale (CAPS-SX17) data were pooled from patients enrolled in two double-blind, randomized, placebo-controlled trials. The CFA was conducted using maximum likelihood and weighted, least-squares factor extraction methods. The EFA was performed using a polychoric correlation covariance matrix and Pearson correlation matrix. Data from a pooled population of 685 patients (venlafaxine ER: n = 339; placebo: n = 346) were analyzed. CFA rejected the DSM-IV three-factor structure. The EFA identified a different three-factor structure as the best fit: factor 1 included reexperiencing symptoms, factor 2 included symptoms of altered mood and cognition, whereas factor 3 comprised avoidance and arousal symptoms. All DSM-IV symptom factors and all factors in the identified three-factor model responded positively to venlafaxine ER treatment. Data are consistent with literature failing to confirm the three-factor structure of DSM-IV PTSD, and they support the DSM-5 inclusion of a symptom cluster addressing altered mood and cognition in PTSD. The efficacy of venlafaxine ER in reducing a range of symptom clusters in PTSD is consistent with its multiple mechanisms of action.
    Brain and behavior. 11/2013; 3(6):738-46.
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    ABSTRACT: Abstract Objective: We tested the Psoriatic Arthritis Screening and Evaluation (PASE) to assess usefulness for psoriatic arthritis (PsA) screening before and after anti-tumor necrosis factor treatment in a clinical trial setting. Methods: Participants of the PRISTINE trial (NCT0066305) were randomized to etanercept 50 mg once weekly or twice weekly. PASE was administered at baseline and 12 weeks of treatment. Scores were compared by a paired sample t-test. Logistic regression and receiver operating curves were used to compare disease assessments against the PASE scores. Results: Participants (N=273, once weekly, n = 137; twice weekly, n = 136) had a mean age of 44 years; 70% were male; mean PASI was 21. At baseline, 31% had a self-reported history of physician-diagnosed PsA (mean duration, 8 years); ∼25% had a PASE total score ≥47, indicating active PsA. At week 12, 14% had scores ≥47 (p = .0143). PASE scores correlated with subject global assessment of joint pain. Conclusions: The PASE was used in a randomized, controlled clinical trial in a moderate to severe psoriasis population with a high prevalence of PsA. Our findings also support the use of PASE as a tool to measure treatment response for PsA.
    Journal of Dermatological Treatment 05/2013; · 1.50 Impact Factor
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    ABSTRACT: BACKGROUND: Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease. METHODS: In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints [DAS28] >3·2 and ≤5·1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15-25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov, number NCT00565409. FINDINGS: 604 (72·4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82·6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42·6%) of 197 who had received placebo (mean difference 40·8%, 95% CI 32·5-49·1%; p<0·0001). Additionally, 159 (79·1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35·9%, 27·0-44·8%; p<0·0001). INTERPRETATION: Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept. FUNDING: Pfizer.
    The Lancet 01/2013; · 39.21 Impact Factor
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    ABSTRACT: Objectives. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite clinical tool combining subjective and objective measures. Using data from the randomized double-blind Ankylosing Spondylitis Study Comparing Enbrel with Sulfasalazine Dosed Weekly (ASCEND) trial, we tested ASDAS validity and assessed its capacity to discriminate between treatment effects and change-from-baseline improvements. Methods. These post hoc analyses were conducted in patients who received etanercept (50 mg/week) or SSZ (≤3 g/day) for 16 weeks. The ASDAS was tested for its capacity to discriminate between those who achieved and did not achieve Assessment of Spondyloarthritis International Society (ASAS) partial remission and ASAS20. Week 16 adjusted treatment differences and effect sizes of improvement from baseline of 42 outcomes were calculated. Results. Means for ASDAS were less than half in patients with ASAS partial remission compared with patients without partial remission across the entire study population (1.2 vs 2.6; P < 0.0001). Patients who achieved ASAS20 had greater mean changes from baseline in ASDAS than those who did not (-1.8 vs -0.3; P < 0.0001). ASDAS was consistently shown to have one of the highest discriminatory capacities compared with other measurements (including subjective measurements) regardless of normal vs high CRP, presence or absence of peripheral arthritis and high vs very high ASDAS at baseline. As a dichotomous variable using different thresholds for improvement and disease severity, ASDAS had slightly better discriminatory capacity than all corresponding ASAS measures. Conclusion. ASDAS is a validated and highly discriminatory tool for the detection of significant differences between treatments for AS as well as for detecting a significant improvement from baseline with etanercept and SSZ.
    Rheumatology (Oxford, England) 07/2012; 51(10):1894-905. · 4.24 Impact Factor
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    ABSTRACT: The objective of this post hoc analysis was to test the benefits of treating very early rheumatoid arthritis (VERA; ≤4 months) using COMET trial data. Treatment response in VERA and early rheumatoid arthritis (ERA; >4 months to 2 years) with combination etanercept+methotrexate (ETN+MTX) or MTX monotherapy was compared. Data assessed at week 52 for baseline disease duration effect included remission (disease activity score (DAS)28 <2.6, SDAI ≤3.3, Boolean), low disease activity (LDA; DAS28 <3.2), Boolean components of remission and radiographic non-progression. Subjects who discontinued because of lack of efficacy were included as non-responders. Higher proportions of VERA subjects achieved LDA (79%) and DAS28 remission (70%) than ERA (62%, 48%, respectively, p<0.05) with ETN+MTX. Such high responses with MTX monotherapy were not observed (VERA, LDA=47%, DAS28 remission=35%; ERA, 47% and 32% respectively, p>0.70 for each). Regardless of disease duration, no radiographic progression was seen in 80% of subjects with ETN+MTX. In contrast, a higher proportion of VERA subjects showed no radiographic progression compared with ERA subjects treated with MTX (73.9% vs 50%, p=0.01). Treatment of VERA with ETN+MTX provides qualitatively improved clinical outcomes not seen with MTX monotherapy, supporting the pivotal role of TNF inhibition in early disease.
    Annals of the rheumatic diseases 03/2012; 71(6):989-92. · 8.11 Impact Factor
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    ABSTRACT: This study aimed to compare the performances of the Modified Composite Psoriatic Disease Activity Index (mCPDAI) and the Disease Activity index for PSoriatic Arthritis (DAPSA) in an interventional study of etanercept in psoriatic arthritis. The components of the CPDAI and DAPSA were extracted using PRESTA (Psoriasis Randomized Etanercept STudy in subjects with psoriatic Arthritis) study data. Data for four of the five domains of the CPDAI-thus an mCPDAI-were available: joints, skin, dactylitis and enthesitis (spinal involvement was not assessed). Domains in the calculation of DAPSA were subjected to global assessment of pain, swollen and tender joint counts, and C reactive protein. were randomised to etanercept 50 mg weekly (n=373) or 50 mg twice weekly (n=379) for 12 weeks; all subjects then received etanercept 50 mg weekly for 12 weeks. The performance of the scores at baseline and on weeks 12 and 24 was compared between the two treatment regimens. The mCPDAI and DAPSA could distinguish response to treatment comparing baseline and 12-week or 24-week values (p<0.0001). The mCPDAI, not DAPSA, could distinguish response between the two treatment groups at 12 weeks (p=0.0492), but not at 24 weeks. All domains evaluated contributed to the data variability of the mCPDAI; the most significant were dactylitis (r=0.64) and enthesitis (r=0.60). In psoriatic arthritis with severe skin involvement, the mCPDAI was able to distinguish treatment response between the two etanercept doses. DAPSA, while demonstrating improvement in both groups over time, was unable to distinguish response between the different doses of etanercept. Further studies are needed to confirm the sensitivity of both indexes.
    Annals of the rheumatic diseases 03/2012; 71(3):358-62. · 8.11 Impact Factor
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    ABSTRACT: Abstract Objective: To assess the efficacy and safety of two etanercept dose regimens for psoriasis treatment. Methods: Subjects were ≥18 years old with stable moderate-to-severe plaque psoriasis. Subjects were randomised to etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) double-blind for 12 weeks, followed by 50 mg QW open label in all subjects through week 24. Only mild topical corticosteroids were permitted on scalp, axillae and groin for first 12 weeks; topical medications (corticosteroids of all potencies, vitamin D analogues and combination products) were allowed as needed for second 12 weeks at physicians' discretion, consistent with "real-world" therapeutic practice. An independent ethics committee reviewed and approved the study protocol. Results: At week 24, 59.9% and 78.2% in the QW/QW and BIW/QW groups achieved PASI 75 improvement. Mean percentage PASI improvement in these groups was 58.5% and 74.1% at week 12 and 70.7% and 81.3% at week 24. Although permitted from weeks 12 to 24, topical agents were used in only 27.7% and 22.6% in the QW/QW and BIW/QW groups by week 24. Conclusion: Both etanercept regimens were efficacious in moderate-to-severe psoriasis, although the BIW/QW regimen consistently provided higher response rates than the QW/QW regimen. More potent topical medications were used electively in <25% of subjects in each group.
    Journal of Dermatological Treatment 01/2012; · 1.50 Impact Factor
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    ABSTRACT: Psoriasis, a chronic inflammatory skin disease, is characterized by periods of remission and relapse of lesions. Etanercept is approved for treatment of moderate-to-severe plaque psoriasis (25 mg twice weekly or 50 mg weekly). This review of three clinical trials evaluated the efficacy and safety of long-term, continuous (≥≥48 weeks) etanercept therapy in 1887 subjects with moderate-to-severe psoriasis (total exposure: 2458.0 subject-years). Efficacy end points across the three studies included: percent subjects achieving improvement of ≥≥75% from baseline in the Psoriasis Area and Severity Index; mean percentage improvement from baseline of Psoriasis Area and Severity Index; mean Physician''s Global Assessment psoriasis score; and Dermatology Life Quality Index total score (mean percentage improvement from baseline). Safety was also assessed. This article summarizes the sustained efficacy of long-term continuous etanercept therapy, which was generally consistent across the three trials. There were no new or unexpected safety signals with up to 144 weeks of continuous etanercept therapy. Long-term continuous etanercept therapy may be an option for some psoriasis patients.
    Expert Review of Dermatology 07/2011; 6(4):361-373.
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    ABSTRACT: To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score < or = 0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission. At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen. Early sustained combination etanercept-MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk.
    Arthritis & Rheumatology 02/2010; 62(3):674-82. · 7.48 Impact Factor
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    ABSTRACT: To compare the efficacy over 12 weeks of two different etanercept regimens in treating the skin manifestations of psoriasis in patients who also have psoriatic arthritis and to evaluate efficacy and safety over an additional 12 weeks of open label etanercept treatment. Design Randomised double blind multicentre outpatient study. 98 outpatient facilities in Europe, Latin America, and the Asia Pacific region. Participants 752 patients with both psoriasis (evaluated by dermatologists) and psoriatic arthritis (evaluated by rheumatologists). During the blinded portion of the study, participants were randomised to receive etanercept 50 mg twice weekly (n=379) or 50 mg once weekly (n=373) for 12 weeks by subcutaneous injection. All participants then received open label etanercept 50 mg once weekly for 12 additional weeks, while remaining blinded to the regimen. The primary efficacy end point was the proportion of participants achieving "clear" or "almost clear" on the physician's global assessment of psoriasis at week 12. Secondary efficacy analyses included psoriasis area and severity index, American College of Rheumatology responses, psoriatic arthritis response criteria, and improvement in joint and tendon disease manifestations. At week 12, 46% (176/379) of participants receiving etanercept 50 mg twice weekly achieved a physician's global assessment of psoriasis of "clear" or "almost clear" compared with 32% (119/373) in the group treated with 50 mg once weekly (P<0.001). In contrast, an equally high percentage of participants in both groups achieved psoriatic arthritis response criteria (77% (284/371) in the twice weekly/once weekly group versus 76% (282/371) in the once weekly/once weekly group). Participants treated with 50 mg twice weekly/once weekly had greater mean reductions from baseline in the psoriasis area and severity index at week 12 compared with those who received 50 mg once weekly/once weekly (71% v 62%, P<0.001), with less difference at week 24 (78% v 74%, P<0.110). Joint and tendon disease manifestations improved from baseline in both groups to a similar extent. No new safety signals were seen in either etanercept treatment group, and no significant difference in the safety profiles was observed. In participants with active psoriasis and psoriatic arthritis, initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than with 50 mg once weekly. A regimen of 50 mg once weekly seems to be appropriate for treatment of joint and tendon rheumatic symptoms. The choice of regimen should be determined by the clinical needs of the individual patient. Clinical trials NCT00245960.
    BMJ (online) 01/2010; 340:c147. · 17.22 Impact Factor
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    ABSTRACT: Objective: To evaluate the efficacy and safety of continuous and paused etanercept regimens in psoriasis patients. Methods: Patients with moderate-to-severe plaque psoriasis were randomized to receive continuous etanercept 25 mg twice weekly or paused etanercept for 54 weeks. The paused group received etanercept 50 mg twice weekly for no more than 12 weeks until reaching a Physician Global Assessment (PGA) of 2 or less (mild or better), when treatment was paused; upon relapse (PGA ≥ 3), etanercept was resumed at 25 mg twice weekly until a PGA of 2 or less was regained. The primary efficacy end point was mean PGA over 54 weeks, which was compared between the continuous and paused groups. Secondary efficacy end points included changes from baseline in mean PGA score, Psoriasis Area and Severity Index (PASI) and patient satisfaction with current psoriasis treatment. Results: Among 711 patients evaluable for efficacy, the mean PGA score averaged over 54 weeks (primary end point) was significantly lower in the continuous etanercept therapy group than in the paused etanercept therapy group (1.98 vs 2.51, respectively; p < 0.001). Mean PGA was significantly reduced from baseline (3.6, both groups) to week 54 in the continuous (1.9) and paused groups (2.4; p < 0.01, within-group comparisons). Mean PASI was significantly decreased from baseline (21.9 and 22.8, respectively) to week 54 with continuous (7.1) and paused therapy (9.5; p < 0.01, within-group comparisons). PASI improved by 68 and 59% from baseline to week 54 in patients receiving continuous and paused etanercept, respectively. Patient satisfaction rates improved from 20.2 and 22.5% in continuous and paused groups, respectively, at baseline to 83.5 and 83.0% at week 12; 83.3 and 78.3% at week 24; and 81.3 and 72.6% at week 54, respectively. Overall, 7.5% (54 out of 720) of patients had serious adverse events (6.4 and 8.5%, continuous and paused groups, respectively); four patients (two per group) had serious infections. No cases of tuberculosis or demyelinating diseases were observed. Conclusion: Both continuous and paused etanercept therapies improved PGA and PASI scores and patient satisfaction rates; patients receiving continuous etanercept therapy showed a greater level of improvement, although those who paused and resumed active treatment generally recaptured response and experienced sustained benefit.
    Expert Review of Dermatology 11/2008; 3(6):657-665.
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    ABSTRACT: Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494). 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p<0.0001). 487 evaluable patients had severe disease (DAS28>5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups. Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. Wyeth Research.
    The Lancet 08/2008; 372(9636):375-82. · 39.21 Impact Factor
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    ABSTRACT: To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.
    Arthritis & Rheumatology 05/2006; 54(4):1063-74. · 7.48 Impact Factor
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    ABSTRACT: To evaluate different methods of presentation and analysis of radiographic data in a rheumatoid arthritis (RA) randomized controlled trial. A double-blind randomized controlled trial including 682 patients with active RA who were treated with methotrexate, etanercept, or a combination of the 2 drugs was used for this study. Probability plots of the change from baseline to year 1 were produced to visualize progression, and were compared with usual descriptive statistics. The primary analysis of the trial (based on annualized actual mean change from baseline in total Sharp score at 1 year, using linear imputation) was challenged using various ways of handling missing information with alternative imputation methods, and by various statistical analyses including analysis of covariance (ANCOVA) and mixed model analysis on both raw and log-transformed data. Probability plots provided detailed insight into the differentiated treatment effects between the 3 arms of this study. As adjuncts to formal hypothesis testing, these plots were more useful for presenting data than were summary descriptive statistics or use of preset cutoff points to define lack of progression. Additional analyses presented here support the results obtained with the per-protocol analysis that showed an advantage of the combination treatment compared with the monotherapy arms and for etanercept versus methotrexate alone. Various ways of handling missing information confirmed the robustness of the results. In addition, both ANCOVA and mixed model analyses on raw and on log-transformed data produced similar results. We suggest a panel of alternative analysis methods and alternative ways of handling missing information to verify that the radiographic results reported in an randomized controlled trial are not influenced by technical factors, such as interpolation, handling of missing data, and choice of statistical tests.
    Arthritis & Rheumatology 02/2005; 52(1):49-60. · 7.48 Impact Factor
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    ABSTRACT: Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.
    The Lancet 02/2004; 363(9410):675-81. · 39.21 Impact Factor

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1k Citations
237.84 Total Impact Points

Institutions

  • 2013
    • Wiener Krankenanstaltenverbund
      Wien, Vienna, Austria
  • 2010
    • Charité Universitätsmedizin Berlin
      • Department of Dermatology, Venerology and Allergology
      Berlin, Land Berlin, Germany
  • 2008–2010
    • University of Leeds
      • Leeds Institute of Molecular Medicine (LIMM)
      Leeds, ENG, United Kingdom
    • University of Nice-Sophia Antipolis
      Nice, Provence-Alpes-Côte d'Azur, France