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Alice B Gottlieb - One of the best experts on this subject based on the ideXlab platform.

  • Etanercept: efficacy and safety for approved indications
    Expert Opinion on Drug Safety, 2011
    Co-Authors: Todd Kerensky, Alice B Gottlieb, Shimrat Yaniv, Shiu-chung Au
    Abstract:

    Introduction: Etanercept is a tumor necrosis factor alpha (TNF-α) inhibitor, which is approved for the treatment of immune-mediated inflammatory conditions including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (PsO). Areas covered: Clinical efficacy and safety data of Etanercept for the approved indications are reviewed in this paper. Data were obtained from published clinical trials, registries, post-marketing data as well as information provided by Amgen. Expert opinion: Etanercept is a generally well-tolerated treatment for the approved inflammatory diseases. The most common adverse effect of Etanercept treatment is injection site reaction, which is generally self-limiting and often does not require treatment. Etanercept may be associated with an increased risk for infection, the development of malignancy, demyelinating disease and congestive heart failure. Fewer patients withdraw from Etanercept due to adverse eve...

  • Etanercept treatment for children and adolescents with plaque psoriasis
    The New England Journal of Medicine, 2008
    Co-Authors: Amy S Paller, Richard G Langley, Alice B Gottlieb, Elaine C Siegfried, David M Pariser, Ian Landells, Adelaide A Hebert, Lawrence F Eichenfield, Vaishali Patel, Kara Creamer
    Abstract:

    A B S T R AC T Background Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of Etanercept in children and adolescents with moderate-to-severe plaque psoriasis. Methods In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of Etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label Etanercept. At week 36, 138 patients underwent a second randomization to placebo or Etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physician’s global assessment of clear or almost clear of disease, and safety assessments. Results At week 12, 57% of patients receiving Etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the Etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physician’s global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001). At week 36, after 24 weeks of open-label Etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to Etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label Etanercept; all resolved without sequelae. Conclusions Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819.)

  • Etanercept treatment for children and adolescents with plaque psoriasis.
    The New England Journal of Medicine, 2008
    Co-Authors: Amy S Paller, Richard G Langley, Alice B Gottlieb, Elaine C Siegfried, David M Pariser, Ian Landells, Adelaide A Hebert, Lawrence F Eichenfield, Vaishali Patel, Kara Creamer
    Abstract:

    A B S T R AC T Background Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of Etanercept in children and adolescents with moderate-to-severe plaque psoriasis. Methods In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of Etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label Etanercept. At week 36, 138 patients underwent a second randomization to placebo or Etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physician’s global assessment of clear or almost clear of disease, and safety assessments. Results At week 12, 57% of patients receiving Etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P

  • long term safety and efficacy of 50 mg of Etanercept twice weekly in patients with psoriasis
    Archives of Dermatology, 2007
    Co-Authors: Stephen K Tyring, Yves Poulin, Kenneth B Gordon, Richard G Langley, Alice B Gottlieb, Meleana Dunn, Angelika Jahreis
    Abstract:

    Objective To evaluate the safety and efficacy of long-term treatment of psoriasis with Etanercept, 50 mg twice weekly. Design, Setting, and Patients A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005. Interventions Patients were randomized to receive placebo or Etanercept for 12 weeks. Beginning with week 13, all patients (N = 591) received Etanercept. Main Outcome Measures Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis. Results Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and Etanercept treatments. Nonneutralizing antibodies to Etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to Etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the Etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label Etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original Etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original Etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%. Conclusions Extended exposure to 50 mg of Etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous Etanercept therapy. Trial Registration clinicaltrials.gov IdentifierNCT00111449.

  • a randomized open label trial of continuous versus interrupted Etanercept therapy in the treatment of psoriasis
    Journal of The American Academy of Dermatology, 2007
    Co-Authors: Angela Yen Moore, Kenneth B Gordon, Alice B Gottlieb, Bruce Freundlich, Sewon Kang, Seth R Stevens
    Abstract:

    Background Although Etanercept is used as a continuous therapy for moderate to severe plaque psoriasis, intermittent use may be necessary in some instances. Objective In this randomized, open-label study, we evaluated the effectiveness and safety of continuous versus interrupted Etanercept therapy. Methods All patients received uninterrupted Etanercept 50 mg twice weekly during the first 12 weeks, followed by either continuous (n = 1272) or interrupted (n = 1274) Etanercept 50 mg once weekly in the next 12 weeks. The primary effectiveness end point was the proportion of responders (those who achieved a Physician's Global Assessment [PGA] score ≤2 and improvement from baseline) at week 24. Secondary end points included the PGA "clear/almost clear" status, the PGA Scalp Psoriasis score, and the Dermatology Life Quality Index. A modified intent-to-treat analysis was performed. Results At week 12, comparable high proportions of responders were reported in the continuous (71.3%) and interrupted (72.0%) arms. However, the proportion of responders at week 24 was greater in the continuous group than in the interrupted group (71.0% vs 59.5%; P Limitations We examined one round of discontinuation and re-treatment; interrupted therapy provided less total medication to responding patients. Conclusions Continuous and interrupted Etanercept therapy was effective and generally well tolerated in patients with psoriasis, with greater improvements observed in the continuous arm at week 24. Most patients regained their response after reinitiation of Etanercept.

Michael Schiff - One of the best experts on this subject based on the ideXlab platform.

  • selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving Etanercept a randomised clinical trial
    Annals of the Rheumatic Diseases, 2006
    Co-Authors: Michael E Weinblatt, Michael Schiff, Joel M Kremer, Allan L Goldman, Michael E Luggen, Tracy Li, Dalei Chen, Jeanclaude Becker
    Abstract:

    Objective: To investigate the efficacy and safety of abatacept in combination with Etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). Methods: Patients continued Etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and Etanercept during the LTE. Results: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and Etanercept versus placebo and Etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and Etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and Etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. Conclusion: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and Etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with Etanercept should not be used for rheumatoid arthritis treatment.

  • Etanercept treatment in adults with established rheumatoid arthritis 7 years of clinical experience
    The Journal of Rheumatology, 2006
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Joel M Kremer, Michael E Weinblatt, Richard W Martin, James B Whitmore, Barbara White
    Abstract:

    OBJECTIVE: To evaluate safety and efficacy of longterm Etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received Etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive Etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of Etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of Etanercept exposure. For 356 patients who completed 6 years of Etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of Etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm Etanercept treatment remains highly favorable.

  • once weekly administration of 50 mg Etanercept in patients with active rheumatoid arthritis results of a multicenter randomized double blind placebo controlled trial
    Arthritis & Rheumatism, 2004
    Co-Authors: Edward C Keystone, Michael Schiff, Joel M Kremer, Shelly Kafka, Michael Lovy, Todd Devries, Daniel J Burge
    Abstract:

    Objective To evaluate the safety, efficacy, and pharmacokinetics of 50 mg Etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA). Methods Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg Etanercept once weekly, 153 received 25 mg Etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg Etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8. Results An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg Etanercept once weekly, by 49% of the patients receiving 25 mg Etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each Etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 Etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 Etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 Etanercept groups. Conclusion Safety, efficacy, and pharmacokinetics were comparable between the 2 Etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with Etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.

  • Etanercept versus methotrexate in patients with early rheumatoid arthritis two year radiographic and clinical outcomes
    Arthritis & Rheumatism, 2002
    Co-Authors: Mark C Genovese, Edward C Keystone, Michael Schiff, Larry W Moreland, Roy Fleischmann, Richard W Martin, Joan M Bathon, John Tesser, Mary Chester M Wasko, Arthur L Weaver
    Abstract:

    Objective To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either Etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy. Methods In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous Etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images. Results At 24 months, more 25-mg Etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg Etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg Etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the Etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events. Conclusion Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.

  • Etanercept therapy in rheumatoid arthritis a randomized controlled trial
    Annals of Internal Medicine, 1999
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Roy Fleischmann, Scott Baumgartner, Elizabeth A Tindall, Ken J Bulpitt, Arthur L Weaver, Daniel E Furst, Philip J Mease
    Abstract:

    Background: In a phase II study, Etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. Objective: To confirm the benefit of Etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. Design: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. Setting: 13 North American centers. Patients: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Intervention: Twice-weekly subcutaneous injections of Etanercept, 10 or 25 mg, or placebo for 6 months. Measurements: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. Results: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of Etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more Etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. Conclusions: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.

Edward C Keystone - One of the best experts on this subject based on the ideXlab platform.

  • Etanercept treatment in adults with established rheumatoid arthritis 7 years of clinical experience
    The Journal of Rheumatology, 2006
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Joel M Kremer, Michael E Weinblatt, Richard W Martin, James B Whitmore, Barbara White
    Abstract:

    OBJECTIVE: To evaluate safety and efficacy of longterm Etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received Etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive Etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of Etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of Etanercept exposure. For 356 patients who completed 6 years of Etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of Etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm Etanercept treatment remains highly favorable.

  • once weekly administration of 50 mg Etanercept in patients with active rheumatoid arthritis results of a multicenter randomized double blind placebo controlled trial
    Arthritis & Rheumatism, 2004
    Co-Authors: Edward C Keystone, Michael Schiff, Joel M Kremer, Shelly Kafka, Michael Lovy, Todd Devries, Daniel J Burge
    Abstract:

    Objective To evaluate the safety, efficacy, and pharmacokinetics of 50 mg Etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA). Methods Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg Etanercept once weekly, 153 received 25 mg Etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg Etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8. Results An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg Etanercept once weekly, by 49% of the patients receiving 25 mg Etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each Etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 Etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 Etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 Etanercept groups. Conclusion Safety, efficacy, and pharmacokinetics were comparable between the 2 Etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with Etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.

  • Etanercept versus methotrexate in patients with early rheumatoid arthritis two year radiographic and clinical outcomes
    Arthritis & Rheumatism, 2002
    Co-Authors: Mark C Genovese, Edward C Keystone, Michael Schiff, Larry W Moreland, Roy Fleischmann, Richard W Martin, Joan M Bathon, John Tesser, Mary Chester M Wasko, Arthur L Weaver
    Abstract:

    Objective To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either Etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy. Methods In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous Etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images. Results At 24 months, more 25-mg Etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg Etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg Etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the Etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events. Conclusion Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.

  • Etanercept therapy in rheumatoid arthritis a randomized controlled trial
    Annals of Internal Medicine, 1999
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Roy Fleischmann, Scott Baumgartner, Elizabeth A Tindall, Ken J Bulpitt, Arthur L Weaver, Daniel E Furst, Philip J Mease
    Abstract:

    Background: In a phase II study, Etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. Objective: To confirm the benefit of Etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. Design: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. Setting: 13 North American centers. Patients: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Intervention: Twice-weekly subcutaneous injections of Etanercept, 10 or 25 mg, or placebo for 6 months. Measurements: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. Results: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of Etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more Etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. Conclusions: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.

Larry W Moreland - One of the best experts on this subject based on the ideXlab platform.

  • Etanercept treatment in adults with established rheumatoid arthritis 7 years of clinical experience
    The Journal of Rheumatology, 2006
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Joel M Kremer, Michael E Weinblatt, Richard W Martin, James B Whitmore, Barbara White
    Abstract:

    OBJECTIVE: To evaluate safety and efficacy of longterm Etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received Etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive Etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of Etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of Etanercept exposure. For 356 patients who completed 6 years of Etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of Etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm Etanercept treatment remains highly favorable.

  • longterm safety efficacy and radiographic outcome with Etanercept treatment in patients with early rheumatoid arthritis
    The Journal of Rheumatology, 2005
    Co-Authors: Mark C Genovese, Larry W Moreland, Wayne Tsuji, Roy Fleischmann, Richard W Martin, James B Whitmore, Joan M Bathon, Jonathan A Leff
    Abstract:

    OBJECTIVE: To evaluate safety, efficacy, and radiographic progression in patients with early rheumatoid arthritis (RA) undergoing longterm treatment with Etanercept. METHODS: Patients with early RA (disease duration of 3 years or less) who had completed a 2-year efficacy study comparing Etanercept and methotrexate (MTX) were followed in an extension where they received 25 mg Etanercept twice weekly. Safety was summarized descriptively and compared with data from the efficacy study. Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria, disease activity scores, and Total Sharp Score (TSS). RESULTS: Rates of serious adverse events and serious infections did not increase with longterm exposure to Etanercept, and were similar to rates reported for the blinded portion of the efficacy study. Efficacy was sustained in patients who completed 5 years of Etanercept treatment at the time of this report (N = 201), even in those who decreased or discontinued use of MTX or corticosteroids. No radiographic progression (change in TSS < or = 0) was seen in 55% of patients with 5-year radiographs; negative change (TSS < 0) was seen in 11%. CONCLUSION: Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years. The results indicate sustained efficacy and decreased rate of radiographic progression. The rate of radiographic progression was low compared with other studies, emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with Etanercept.

  • combination therapy with Etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate
    Arthritis & Rheumatism, 2004
    Co-Authors: Mark C Genovese, Stanley N Cohen, Larry W Moreland, Deborah Lium, Sean Robbins, Richard Newmark, Pirow Bekker
    Abstract:

    Objective To determine the potential for additive or synergistic effects of combination therapy with the selective anti–tumor necrosis factor α agent Etanercept and the anti–interleukin-1 agent anakinra. Methods Two hundred forty-four patients in whom rheumatoid arthritis (RA) was active despite methotrexate therapy were treated with subcutaneous Etanercept only (25 mg twice weekly), full-dosage Etanercept (25 mg twice weekly) plus anakinra (100 mg/day), or half-dosage Etanercept (25 mg once weekly) plus anakinra (100 mg/day) for 6 months in a double-blind study at 41 centers in the US. Patients had never previously received anticytokine therapy. Patient response was measured with the American College of Rheumatology (ACR) core set criteria, a health-related quality-of-life questionnaire, and the Disease Activity Score. Safety was assessed by the number of adverse events and clinical laboratory values. Plasma concentrations of both agents and antibody formation against both agents were also assessed. Results Combination therapy with Etanercept plus anakinra provided no treatment benefit over Etanercept alone, regardless of the regimen, but was associated with an increased safety risk. Thirty-one percent of the patients treated with full-dosage Etanercept plus anakinra achieved an ACR 50% response, compared with 41% of the patients treated with Etanercept only. This result was not statistically significant (P = 0.914). The incidence of serious infections (0% for Etanercept alone, 3.7–7.4% for combination therapy), injection-site reactions, and neutropenia was increased with combination therapy. Combination therapy had no effect on the pharmacokinetics or immunogenicity of either agent. Conclusion Combination therapy with Etanercept and anakinra provides no added benefit and an increased risk compared with Etanercept alone and is not recommended for the treatment of patients with RA.

  • Etanercept versus methotrexate in patients with early rheumatoid arthritis two year radiographic and clinical outcomes
    Arthritis & Rheumatism, 2002
    Co-Authors: Mark C Genovese, Edward C Keystone, Michael Schiff, Larry W Moreland, Roy Fleischmann, Richard W Martin, Joan M Bathon, John Tesser, Mary Chester M Wasko, Arthur L Weaver
    Abstract:

    Objective To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either Etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy. Methods In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous Etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images. Results At 24 months, more 25-mg Etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg Etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg Etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the Etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events. Conclusion Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.

  • Etanercept therapy in rheumatoid arthritis a randomized controlled trial
    Annals of Internal Medicine, 1999
    Co-Authors: Larry W Moreland, Edward C Keystone, Michael Schiff, Roy Fleischmann, Scott Baumgartner, Elizabeth A Tindall, Ken J Bulpitt, Arthur L Weaver, Daniel E Furst, Philip J Mease
    Abstract:

    Background: In a phase II study, Etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. Objective: To confirm the benefit of Etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. Design: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. Setting: 13 North American centers. Patients: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Intervention: Twice-weekly subcutaneous injections of Etanercept, 10 or 25 mg, or placebo for 6 months. Measurements: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. Results: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of Etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more Etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. Conclusions: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.

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  • once weekly administration of 50 mg Etanercept in patients with active rheumatoid arthritis results of a multicenter randomized double blind placebo controlled trial
    Arthritis & Rheumatism, 2004
    Co-Authors: Edward C Keystone, Michael Schiff, Joel M Kremer, Shelly Kafka, Michael Lovy, Todd Devries, Daniel J Burge
    Abstract:

    Objective To evaluate the safety, efficacy, and pharmacokinetics of 50 mg Etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA). Methods Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg Etanercept once weekly, 153 received 25 mg Etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg Etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8. Results An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg Etanercept once weekly, by 49% of the patients receiving 25 mg Etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each Etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 Etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 Etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 Etanercept groups. Conclusion Safety, efficacy, and pharmacokinetics were comparable between the 2 Etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with Etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.

  • Etanercept in the treatment of psoriatic arthritis and psoriasis a randomised trial
    The Lancet, 2000
    Co-Authors: Philip J Mease, Bernard S Goffe, James Metz, Ann Vanderstoep, Barbara K Finck, Daniel J Burge
    Abstract:

    Summary Background Etanercept, a tumour-necrosis-factor inhibitor, has shown efficacy in the treatment of rheumatoid arthritis. Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor, a proinflammatory cytokine, is present in increased concentrations in joints and in the skin. Therefore, psoriatic arthritis and psoriasis may be appropriate therapeutic targets for Etanercept. Methods This randomised, double-blind, placebo-controlled, 12 week study assessed the efficacy and safety of Etanercept (25 mg twice-weekly subcutaneous injections) or placebo in 60 patients with psoriatic arthritis and psoriasis. Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria (PsARC) and who met the American College of Rheumatology preliminary criteria for improvement (ACR20). Psoriasis endpoints included improvement in the psoriasis area and severity index (PASI) and improvement in prospectively-identified individual target lesions. Findings In this 12 week study, 26 (87%) of Etanercept-treated patients met the PsARC, compared with seven (23%) of placebo-controlled patients. The ARC20 was achieved by 22 (73%) of Etanercept-treated patients compared with four (13%) of placebo-treated patients. Of the 19 patients in each treatment group who could be assessed for psoriasis (≥3% body surface area), five (26%) of Etanercept-treated patients achieved a 75% improvement in the PASI, compared with none of the placebo-treated patients (p=0·015). The median PASI improvement was 46% in Etanercept-treated patients versus 9% in placebo-treated patients; similarly, median target lesion improvements were 50% and O, respectively. Etanercept was well tolerated. Interpretation Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease.