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At least 19 recordsLinked to original sources
PubMed2003

Etanercept versus etanercept plus methotrexate: a registry-based study suggesting that the combination is clinically more efficacious.

Etanercept can be used both as monotherapy and in combination with methotrexate (MTX), but direct comparisons of these two options have not yet been reported. In order to compare the results seen in actual practice between these two options, clinical data on 97 patients followed in the Stockholm TNFalpha Follow-Up Registry were analysed. In 57 of these patients etanercept was added to previously started MTX while the others were treated with etanercept alone. The two groups had similar levels of disease activity at baseline. After 3 months, a significantly lower mean disease activity score (28-joint count-based disease activity score) was attained by the patients on etanercept plus MTX. In this group, the number of patients achieving European League Against Rheumatism-defined remission was also significantly greater. Other disease outcomes showed non-significant trends in the same direction. These data suggest that the combination of etanercept plus MTX is clinically more efficacious than etanercept alone.

Arthritis, Rheumatoid↗
PubMed2006

Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes.

OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.

Antirheumatic Agents↗
PubMed2006

Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study.

OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) monotherapy compared with combination ETN and methotrexate (MTX) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.) METHODS: Patients with active rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included in this 16 week, randomised, open-label study. Patients were randomly assigned to either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose of MTX or ETN monotherapy. RESULTS: 315 patients were randomised to ETN (n = 160) or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2 units, was achieved by 72.8% and 75.2% of patients treated with ETN and those treated with ETN plus MTX, respectively, with no significant difference (p = 0.658) between the two groups. The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0% of patients in the ETN group and by 82.4% of patients in the ETN plus MTX group. American College of Rheumatology 20%, 50% and 70% response rates achieved by both groups were also similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates of adverse and serious adverse events were similar between the treatment groups. CONCLUSION: Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX resulted in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis.

Adult↗
PubMed2006

Etanercept and efalizumab for the treatment of psoriasis: a systematic review.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and efalizumab for the treatment of moderate to severe chronic plaque psoriasis. DATA SOURCES: Major electronic databases and several Internet resources were searched up to April 2004. REVIEW METHODS: Systematic reviews were undertaken of the efficacy, safety and economic reviews of etanercept and efalizumab. An existing systematic review of the efficacy and safety of other treatments was also updated. Economic models supplied by the manufacturers of etanercept and efalizumab were critiqued. An economic model was then developed of etanercept and efalizumab in the treatment of moderate to severe chronic plaque psoriasis. RESULTS: The review of the clinical evidence identified a total of 39 published and three unpublished studies: eight randomised controlled trials (RCTs) of the efficacy of etanercept (three trials) and efalizumab (five); 10 studies of the adverse effects of the interventions; and 24 RCTs of the efficacy of the other treatments for moderate to severe psoriasis. The trials of the efficacy of the interventions were all double-blind and placebo-controlled trials and generally of good quality, but three of the five efalizumab trials were poorly reported. A total of 1347 patients were included in the etanercept trials and 2963 in the efalizumab trials. Data on the efficacy of etanercept 25 mg twice a week for 12 weeks were available from three RCTs. On average, active treatment resulted in 62% of patients achieving a Psoriasis Area and Severity Index (PASI) 50, 33% achieving a PASI 75, 11% achieving a PASI 90 and 40% were assessed as clear or almost clear. These figures are not adjusted for changes relative to placebo. Improvement in quality of life as assessed by mean percentage change in Dermatology Life Quality Index (DLQI) was around 59% with etanercept 25 mg twice a week compared with 9% with placebo, and all mean differences that could be calculated were statistically significantly in favour of etanercept. Data on the efficacy of etanercept 50 mg twice a week for 12 weeks were available from two RCTs. Across the two trials, the proportion of patients achieving PASI 50, 75 and 90 was 76, 49 and 21%, respectively; the pooled relative risks were all statistically significantly in favour of etanercept. The findings for mean PASI after treatment, mean percentage change in PASI from baseline and mean percentage change in DLQI also demonstrated the efficacy of etanercept treatment. Evidence from one RCT indicates that the response to etanercept is maintained post-treatment, at least in the medium term, and data from uncontrolled follow-up phases reflect and extend these findings. Efalizumab at a dose of 1 mg/kg once a week subcutaneously was studied in five RCTs. Across these trials, 12 weeks of active treatment resulted in an average of 55% of patients achieving PASI 50, 27% PASI 75, 4.3% PASI 90 and 27% clear or minimal psoriasis status. These figures are not adjusted for changes relative to placebo. There is no evidence from RCTs that the response to efalizumab 1 mg/kg once a week is maintained when treatment continues beyond 12 weeks, and long-term follow-up data relate to a range of doses and are poorly reported and so cannot be used to draw even tentative conclusions regarding the long-term efficacy of efalizumab. Uncontrolled data from trial follow-up suggest that time to relapse may be around 60 days. No data indicating the existence or absence of any rebound in psoriasis after discontinuation of efalizumab were identified. There is no evidence relating to the efficacy of efalizumab upon retreatment. A mixed treatment comparison analysis found a higher response rate in terms of PASI 50, 75 and 90 with etanercept than with efalizumab. Injection site reactions appear to be the most common adverse effects of etanercept. Overall, etanercept appears to be well tolerated in short- and long-term use, although many of the long-term data are not from patients with psoriasis. Headache, chills and, to a lesser extent, nausea, myalgia, pain and fever are the common adverse events associated with efalizumab. Overall, withdrawal rates due to adverse events are low. Longer term data for efalizumab are not readily available for evaluation, but the adverse events data up to 3 years appear to reflect those over 12 weeks and to remain stable. Unfortunately, few data for serious infections and serious adverse events with efalizumab are available. For the primary analysis comparing etanercept, efalizumab and supportive care, the results of the York Model suggest that the biological therapies would only be cost-effective for all patients with moderate to severe psoriasis if the NHS were willing to pay over pound 60,000 per QALY gained. In patients with poor baseline quality of life (fourth quartile DLQI), efalizumab, etanercept 25 mg (intermittent), etanercept 25 mg (continuous) and etanercept 50 mg (intermittent) would be cost-effective as part of a treatment sequence if the NHS were willing to pay pound 45,000, pound 35,000, pound 45,000 and pound 65,000 per QALY gained, respectively. In patients who are also at high risk of inpatient hospitalisation (21 days per annum), these therapies would be cost-effective as part of a sequence as long as the NHS were willingness to pay pound 25,000, pound 20,000, pound 25,000 and pound 45,000 per QALY gained, respectively. As part of a secondary analysis including a wider range of systemic therapies as comparators, the York Model found that it would only be cost-effective to use etanercept and efalizumab in a sequence after methotrexate, ciclosporin and Fumaderm. CONCLUSIONS: Clinical trial data indicate that both etanercept and efalizumab are efficacious in patients who are eligible for systemic therapy, but the economic evaluation demonstrates that these biological therapies are likely to be cost-effective only in patients with poor baseline QoL and who are at risk of hospitalisation. Efficacy trials conducted in the specific population for which etanercept and efalizumab are licensed are required, as are long-term comparisons of etanercept and efalizumab with other treatments for moderate to severe psoriasis. Long-term efficacy trials and safety/tolerability data for patients treated with etanercept or efalizumab are required, as are trials on the response of specific subtypes of psoriasis to different drugs. Research on the rate of inpatient hospitalisation in patients with moderate to severe psoriasis is warranted, and the effect of treatment on this rate.

Antibodies, Monoclonal↗
PubMed2006

Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have inadequate response to standard treatment, including disease-modifying antirheumatic drug (DMARD) therapy. DATA SOURCES: Electronic databases were searched up to July 2004. REVIEW METHODS: A systematic review evaluated the clinical efficacy and adverse effects of etanercept and infliximab. The efficacy of DMARDs in the treatment of PsA was also reviewed and treatments were compared using Bayesian evidence synthesis methods. Following evaluation of existing economic evaluations of etanercept and infliximab in PsA, a new economic model was developed (the York Model). This utilised the results from the evidence synthesis and data from a range of other sources. RESULTS: Across the two trials, at 12 weeks, around 65% of patients treated with etanercept achieved an American College of Rheumatology (ACR) 20 {pooled relative risk (RR) 4.19 [95% confidence interval (CI) 2.74 to 6.42]}, demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. In addition, around 45% of patients treated with etanercept achieved an ACR 50 [pooled RR 10.84 (95% CI 4.47 to 26.28)] and around 12% achieved an ACR 70 [pooled RR 16.28 (95% CI 2.20 to 120.54)], demonstrating a good level of efficacy. The subgroup analyses conducted in one trial revealed that the effect of etanercept was not dependent upon patients' concomitant use of methotrexate. In addition, almost 85% of patients treated with etanercept achieved a Psoriatic Arthritis Response Criteria (PsARC) [pooled RR 2.60 (95% CI 1.96 to 3.45). The Psoriatic Area and Severity Index (PASI) results indicate some beneficial effect on psoriasis at 12 weeks; however, the data are sparse. The statistically significant reduction (improvement) in Health Assessment Questionnaire (HAQ) score with etanercept compared with placebo indicates a beneficial effect of etanercept on function. Similar results were seen at 24 weeks, except that the results for PASI 75 and PASI 50 now achieved statistical significance and data for Total Sharp Score annualised rate of progression were available; this was statistically significantly lower in etanercept-treated patients than in placebo-treated patients. Uncontrolled follow-up of patients indicates that treatment benefit may be maintained for at least 50 weeks. At 16 weeks, 65% of patients treated with infliximab achieved an ACR 20 [RR 6.80 (95% CI 2.89 to 16.01)], demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. This level of efficacy was not dependent upon patients' concomitant use of methotrexate. Almost half the patients treated with infliximab achieved an ACR 50 [RR 49.00 (95% CI 3.06 to 785.06)] and over one-quarter achieved an ACR 70 [RR 31.00 (95% CI 1.90 to 504.86)] compared with none of the placebo group, demonstrating a good level of efficacy. In addition, 75% of patients treated with infliximab achieved a PsARC [RR 3.55 (95% CI 2.05 to 6.13)]. The beneficial treatment effect on psoriasis was also statistically significant with a mean difference in percentage change from baseline in PASI of -5 (95% CI -6.8 to -3.3), as was the percentage improvement from baseline in HAQ score with infliximab compared with placebo [mean difference 51.4 (95% CI 48.08 to 54.72)], indicating a beneficial effect of infliximab on functional status. Uncontrolled data from all measures of joint disease, psoriasis and HAQ collected up to 50 weeks of follow-up reflect those at 16 weeks. There were no radiographic assessments, so nothing can be determined about the potential or otherwise of infliximab to delay the progression of joint disease. Using the York cost-effectiveness model, infliximab was consistently dominated by etanercept because of its higher acquisition and administration costs without superior effectiveness. The incremental cost per quality-adjusted life-year (QALY) gained of etanercept compared with palliative care ranged from 14,818 pounds (females, 40-year time horizon) to 49,374 pounds (males, 1-year time horizon) if it is assumed that, when patients eventually fail on biological therapy, their disability (in terms of HAQ score) deteriorates by the same amount as it improved when they initially respond to treatment (rebound equal to gain). Results for etanercept ranged from 25,443 pounds (females, 40-year time horizon) to 49,441 pounds (males, 1-year time horizon) per QALY gained under the assumption that, when patients fail on therapy, their disability level returns to what it would have been had they never responded (rebound equal to natural history). CONCLUSIONS: The limited data available indicated that etanercept and infliximab are efficacious in the treatment of PsA with beneficial effects on both joint and psoriasis symptoms and on functional status. Short-term data indicated that etanercept can delay joint disease progression, but long-term data are needed. There are no controlled data as yet to indicate that infliximab can delay joint disease progression. Treatment with both etanercept and infliximab for 12 weeks demonstrated a significant degree of efficacy, with no statistically significant difference between them. For both drugs, adverse events were common with mild injection/infusion reactions being the main treatment-related effect. The York model indicated that etanercept is more cost-effective than infliximab as it has a lower cost with little difference in outcomes. The cost-effectiveness of etanercept is also sensitive to assumptions made about the extent of disease progression when patients are responding to therapy. The number of years for which a patient can be safely on biologicals is uncertain so these results should be considered with caution. Further research should include long-term controlled trials to confirm benefits, review adverse events and to explore further the implications of biologic therapy.

Anti-Inflammatory Agents↗
PubMed2003

Etanercept for the treatment of rheumatoid arthritis.

BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five electronic databases were searched from 1966 to February 2003 with no language restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6 month duration) comparing three possible combinations 1) etanercept (10 mg or 25 mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3) etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed the methodological quality of the trails. The American College of Rheumatology (ACR) core set of disease activity measures for RA clinical trials, radiographic, withdrawals and toxicity outcomes were analyzed. MAIN RESULTS: Three trials were included in this review. Two trials compared an experimental group who were started on etanercept compared to a control group; both groups had the same ongoing background therapy of nonsteroidals in both trials plus in one trial one group was on stable methotrexate. In these two trials the ACR 20, ACR 50 and ACR 70 response rates at 6 months were statistically significantly and clinically important with etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of people receiving etanercept ache vied an ACR 20 response compared to 15% of controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty-nine percent of those receiving etanercept achieved an ACR 50 response compared to 4% of taking control treatment and the NNT is three. Fifteen percent of people taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7 people. In the third trial of starting etanercept compared to starting methotrexate the number of participants who achieved an ACR 20, 50 or response at 6 and 12 months were not statistically significant for either etanercept dose. Etanercept treatment showed a statistically significantly and clinically important affect on joint damage as measured by the Sharp erosion score. Among participants who received etanercept 72% had no increase in their erosion score compared to 60% of participants in the methotrexate group. Withdrawal and toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at 6 months, and over 12 months it slowed joint damage.

Antirheumatic Agents↗
PubMed1999

Etanercept: a review of its use in rheumatoid arthritis.

UNLABELLED: Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-alpha and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis. In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with > or = 1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures. A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by <25% in patients treated with placebo. In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years. Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time. Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged > or =4 years with refractory juvenile rheumatoid arthritis. Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept- than placebo-treated patients, but did not bias the results of any study. CONCLUSIONS: When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.

Animals↗
PubMed2004

Unaltered etanercept pharmacokinetics with concurrent methotrexate in patients with rheumatoid arthritis.

The purpose of this study was to evaluate the potential impact of concurrent weekly oral methotrexate administration on the pharmacokinetics of etanercept in patients with rheumatoid arthritis (RA) in a phase 3B trial. As part of a double-blind randomized trial of 682 patients with rheumatoid arthritis who received etanercept (25 mg subcutaneously twice weekly), methotrexate (weekly oral dose, median weekly dose: 20 mg), or etanercept (25 mg subcutaneously twice weekly) plus methotrexate (weekly oral dose, median weekly dose: 20 mg), serum etanercept concentrations were measured in a subset of patients. Serum samples for 98 randomly selected patients (48 receiving etanercept-alone treatment, 50 receiving etanercept plus methotrexate combination treatment) were analyzed to assess the pharmacokinetics of etanercept. A single blood sample was drawn from each patient at baseline and at the week 24 visit. Given the variable sampling time for patients in both groups, a population pharmacokinetic analysis using NONMEM was conducted for etanercept. A final covariate population pharmacokinetic model was constructed based on previously obtained etanercept data from both healthy subjects (n = 53) and patients with RA (n = 212) in 10 prior clinical trials. The predictive performance of the final model was assessed by both bootstrap and data-splitting validation approaches. The final model was then used to estimate Bayesian pharmacokinetic parameters for the patients in both treatments in the current trial. The potential effect of the concurrent administration of methotrexate on the pharmacokinetics of etanercept was examined by comparing the clearance values between 2 treatments using statistical criteria. A population 2-compartment model with first-order elimination from the central compartment and with either zero-order (intravenous administration) or first-order (subcutaneous administration) input was selected based on the data from the prior 10 etanercept clinical studies. The following pharmacokinetic parameters (typical value +/- standard error) were estimated: clearance (CL: 0.072 +/- 0.005 L/h), volume of distribution in the central compartment (V(c): 5.97 +/- 0.45 L), volume of distribution in the peripheral compartment (V(p): 2.05 +/- 0.32 L), intercompartment clearance (Q: 0.0645 +/- 0.0093 L/h), first-order absorption rate constant (k(a): 0.0282 +/- 0.0039 1/h), and absolute bioavailability for subcutaneous administration (F: 0.626 +/- 0.056). Interindividual variability of the pharmacokinetic parameters was quantified for CL (25.1%), V(c) (41.7%), k(a) (53.1%), and F (24.2%). Residual variability consisted of combined additive (11.4 ng/mL) and proportional error (49.9%). Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on CL. The results of both validation tests indicated the adequate predictive performance of the population model. Based on the bioequivalence criteria, the Bayesian-estimated clearance for patients receiving etanercept alone (mean: 0.070 L/h) was comparable to that for patients receiving a combination of etanercept and methotrexate (mean = 0.066 L/h). The pharmacokinetics of etanercept were not altered by the concurrent administration of methotrexate in patients with rheumatoid arthritis. Thus, no etanercept dose adjustment is needed for patients taking concurrent methotrexate.

Antirheumatic Agents↗
PubMed2005

Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial.

BACKGROUND: Etanercept, a soluble tumour necrosis factor receptor, lessens the severity of psoriasis as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life. OBJECTIVES: To assess patient-reported outcomes (PROs) in patients with psoriasis receiving etanercept therapy. METHODS: In this multinational, randomized, phase III trial, patients with psoriasis received placebo (n = 193), etanercept 50 mg per week (n = 196) or etanercept 50 mg twice weekly (n = 194) during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week). The following PROs were assessed: Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis. RESULTS: At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo (P < 0.0001), and improvement in DLQI was clinically meaningful (> or = 5-point improvement or 0 score) for 72-77% of patients receiving etanercept therapy. All DLQI and SF-36 subscales and the SF-36 physical and mental component summary scores demonstrated significantly greater improvement with etanercept therapy than with placebo, illustrating that etanercept benefits patients with psoriasis across multiple domains that contribute to health-related quality of life. With etanercept therapy, distributions of patient ratings of pruritus and global assessment of disease shifted from moderate to severe (baseline) to minimal to good (week 12). Etanercept-induced benefits of PROs were maintained for patients who reduced their dose after 12 weeks. CONCLUSIONS: Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.

Adult↗
PubMed2007

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Adult↗
PubMed2002

Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis.

Etanercept is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59 to 75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11 to 14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a >or=30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.

Adolescent↗
PubMed2003

Spotlight on etanercept in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis.

Etanercept (Enbrel) is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59-75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11-14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a > or =30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2006

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison.

OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. METHODS: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p<0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p<0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p<0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p<0.05), but infections and injection site reactions were higher with etanercept alone (p<0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. CONCLUSIONS: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.

Adult↗
PubMed2005

No evidence for increased risk of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis receiving etanercept for up to 5 years.

OBJECTIVE: To determine the incidence of cutaneous squamous cell carcinoma (SCC) in patients with rheumatoid arthritis receiving etanercept, a tumor necrosis factor antagonist, for up to 5 years. DESIGN: An etanercept clinical trials' database and an etanercept postmarketing surveillance database were retrospectively analyzed for the incidence of SCC. SETTING: Patients enrolled in clinical trials of etanercept were from private and institutional practices. The postmarketing database comprised reports from postmarketing trials and solicited and spontaneous reports. Patients A total of 1442 patients with rheumatoid arthritis with 4257 patient-years of etanercept exposure (median exposure, 3.7 years) are included in the clinical trials' database. More than 125,000 patients with more than 250,000 patient-years of etanercept exposure are included in the etanercept postmarketing database. Interventions Most patients enrolled in clinical trials of etanercept received a dosage of 25 mg of etanercept subcutaneously twice weekly for most of the time they received etanercept therapy. RESULTS: Only 4 cases of SCC were observed in the etanercept clinical trials' database, an incidence that compares favorably with the expected incidences based on general population data from Arizona (13.1) and Minnesota (5.9). Similarly, few cases of SCC (1 per 10,000 patient-years) have been reported during postmarketing surveillance of etanercept therapy. CONCLUSION: In patients with rheumatoid arthritis, etanercept use of up to 5 years does not seem to be associated with an increase in the incidence of cutaneous SCC.

Adult↗