Study Designs and References

Study Designs

+ -
The Early RA Trial and Open-label Extension Trial
Expand/Collapse

The Early RA Trial and Open-label Extension Trial1-5:

  • Multicenter, double-blind, double-dummy, phase 3 trial
  • 632 MTX-naive patients with moderate to severe early RA (≤3 years' duration) were randomized to receive twice-weekly ENBREL 25 mg (n = 207), twice-weekly ENBREL 10 mg (n = 208), or MTX (n = 217). The mean duration of disease for these patients was 11 months
  • This trial became open-label and unblinded after all patients had completed 1 year of evaluation. Patients continued through 1 year of follow-up on the treatment to which they had been randomized. At end of year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously
  • Subjects could re-enroll in the continuing open-label portion of the study upon meeting specific predefined re-enrollment inclusion criteria

References

  1. Enbrel® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
  2. Data on file, Amgen.
  3. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.
  4. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.
  5. Genovese MC, Bathon JM, Fleischmann RM, et al. Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.
The COMET Trial
Expand/Collapse

The COMET Trial1-3:

Year 1

  • 24-month, randomized, double-blind, two-period trial of 542 patients with moderately to severely active RA (from ≥3 months' to ≤2 years' duration). Mean duration of disease for these patients was 9 months
  • At baseline: patients were ≥18 years of age, were MTX-naive, had a DAS 28 ≥3.2, had either an erythrocyte sedimentation rate (ESR) ≥28 mm/hr or C-reactive protein (CRP) level ≥20 mg/L, and were within ACR Functional Class I, II, or III
  • Corticosteroids (≤10 mg prednisone or equivalent) and NSAIDs were allowed if the dose was stable for at least 4 weeks prior to baseline. The doses were required to be kept constant through 24 weeks unless the patient experienced an adverse event. DMARDs other than MTX and ENBREL were not allowed

Study Design1,2:

  • The 2-year COMET trial was divided into two periods, each lasting 1 year
  • The primary objective was to compare the effects of ENBREL + MTX to MTX on clinical disease activity and radiographic change over 1 year (Period 1) in subjects with active early RA
  • Results for both 1- and 2-year analyses should be viewed in context with the populations evaluated for each time point
  • During Period 1 of the trial, patients were randomized to receive once-weekly ENBREL 50 mg in combination with weekly MTX (n = 274) or MTX alone (n = 268). In both the combination and monotherapy groups, initial MTX therapy dose was 7.5 mg, which was titrated to 15 mg at Week 4 if response was inadequate, and further titrated at Week 8 if patients still responded inadequately (maximum dose was 20 mg/week)
  • From Weeks 8 to 52, the mean (median) MTX therapy doses were: ENBREL + MTX = 16 mg/week (17 mg/week); MTX monotherapy = 17 mg/week (20 mg/week)

Treatment Groups1,2:

  • Subjects were randomized at the baseline visit equally to 1 of 4 groups
    • Group 1A: ENBREL + MTX in Periods 1 and 2
    • Group 1B: ENBREL + MTX in Period 1 and ENBREL alone in Period 2
    • Group 2A: MTX alone in Period 1 and ENBREL + MTX in Period 2
    • Group 2B: MTX in Periods 1 and 2
  • 131 (24.2%) subjects discontinued during Year 1 of the study: 79 (29.5%) in the MTX group and 52 (19%) in the ENBREL + MTX treatment group

1-Year Endpoints2:

  • Clinical endpoints included: DAS 28 clinical remission at Month 12, DAS 44 clinical remission, and ACR 20/50/70
  • Radiographic endpoint: change in mTSS at Month 12 (components of TSS are joint space narrowing and joint erosion scores)

Safety Analyses1,2:

  • Safety was analyzed using the intent-to-treat (ITT) population (N = 542), which was defined as all enrolled subjects in the trial who received at least 1 dose of the study drug

Efficacy Analyses2:

  • The primary clinical efficacy endpoint was DAS 28 clinical remission (<2.6) at Month 12
  • For Period 1 analyses, the modified ITT (mITT) population included all subjects who received at least 1 dose of drug and had baseline and ≥1 postbaseline DAS 28 results (N = 265 for ENBREL + MTX, N = 263 for MTX alone)
  • The primary radiographic endpoint was the change in mTSS over 12 months
  • Radiographic analyses for Period 1 included only subjects with baseline and follow-up x-rays (N = 246 for ENBREL + MTX, N = 230 for MTX alone)
 

Year 2

 *One subject (Group 1B) discontinued at final Year 1 visit but received 1 dose of the study drug in Year 2 and was included in the Year 2 population.

Study Design1,2:

  • The MTX or MTX-matching placebo dose level at the end of Period 1 was the starting dose level for MTX or MTX-matching placebo in Period 2. Subjects in Group 1B (ENBREL + MTX/ENBREL) discontinued MTX by the end of the fourth week of Period 2 (ie, by the start of Month 13 of the study). In Year 2, the mean doses of MTX (mg/week) were similar between groups: 16.19 in Group 1A, 16.26 in Group 1B (mean MTX dose reported was specific to the withdrawal period [~4 weeks]), 17.83 in Group 2A, and 18.03 in Group 2B

Treatment Groups1:

  • Subjects who met inclusion criteria for Period 1 and completed Period 1 were eligible to participate in Period 2
  • No re-randomization of subjects in Year 2
  • 64 patients discontinued during Year 2: 7 in Group 1A, 16 in Group 2A, 18 in Group 1B, and 23 in Group 2B

2-Year Endpoints1:

  • Evaluate the safety of each treatment group during Year 2
  • Compare the effects of ENBREL + MTX to MTX alone on radiographic change and clinical disease activity in Period 2 in subjects who first received MTX alone for 1 year
  • Compare the effects of ENBREL + MTX to ENBREL alone on radiographic change and clinical disease activity in Period 2 in subjects who first received ENBREL + MTX for 1 year
  • Compare the effects of ENBREL + MTX for 2 years to MTX alone for 1 year, followed by ENBREL + MTX on radiographic change and clinical disease activity over 2 years
  • Compare the effects of ENBREL + MTX on radiographic change and clinical disease activity to MTX alone over 2 years

Safety Analyses1,2:

  • The ITT population (N = 411) was defined as all subjects who received at least 1 dose of study drug during Period 2

Efficacy Analyses1:

  • The mITT population was defined as all subjects who received at least 1 dose of study drug and had Year 2 baseline and ≥1 post-Year 2 baseline DAS 28 results
    • For other analyses, fewer subjects may have been included if they were missing data for that particular endpoint
  • Data analyses performed upon completion of Year 2 included data generated by subjects during Year 1 of the COMET trial
  • There were 2 baselines for Year 2 analyses: the original baseline at the beginning of Year 1 and the Year 2 baseline (Week 52)
  • The radiographic ITT population received at least 1 dose of study drug and provided data at baseline, Year 1, and during Year 2
  • Nonresponder imputation (NRI) population analyses included patients who received at least 1 dose of study drug and had at least 1 post-Year 1 baseline on-therapy ACR result (N = 488)

References

  1. Data on file, Pfizer Inc.
  2. Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
  3. Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992;35:498-502.
Explanation of Non-Prespecified Data Analysis
Expand/Collapse

Explanation of Non-Prespecified Data Analysis

The COMET trial: A very early non-prespecified analysis

  • The COMET trial was not prospectively designed to compare patients with very early RA to those with early RA. Data from the non-prespecified analysis should be viewed in context with the results from the prospective analysis of the COMET trial. The interpretation of the results of non-prespecified analyses is limited. For instance, these analyses were performed following the unblinding of the data when all patient responses were known
  • A non-prespecified analysis of COMET trial observed data was done to determine if very early (≤4 months' disease duration) compared with early (>4 months' to 2 years' duration) treatment of moderate to severe RA was associated with a higher percentage of patients achieving DAS 28 clinical remission at 52 weeks (DAS 28 ≤2.6)
  • This analysis included only patients with a DAS 28 score at 52 weeks and those who discontinued for lack of efficacy and who were assumed to be non-responders
    • Of 274 randomized to ENBREL + MTX, 220 were included in this analysis: 63 in the very early group and 157 in the early group
    • Of 268 randomized to MTX only, 197 were included in this analysis: 49 in the very early group and 148 in the early group
  • Subjects who achieved the following outcomes at Week 52 were assessed by treatment group for baseline disease duration effect
    • Clinical remission
    • LDA
    • HAQ ≤0.5
    • Radiographic nonprogression (Δ mTSS ≤0.5)
The Long-standing RA Open-label Extension Trial
Expand/Collapse

The Long-Standing RA Open-Label Extension Trial1,2:

  • 714 adult patients with moderately to severely active RA (mean duration of disease = 12 years) who had previously inadequate response to one or more DMARDs and had received ENBREL either as monotherapy or in combination with MTX in various clinical trials
  • Use of concomitant corticosteroids and/or NSAIDs was permitted during the study
  • Most patients received ENBREL 25 mg twice weekly. Because all patients did not enter clinical trials at the same time, length of follow-up varies
  • All 714 adult patients who received at least one dose of ENBREL were evaluated for safety. There was no active control or placebo arm in this open-label extension

References

  1. Moreland LW, Weinblatt ME, Keystone EC, et al. Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical experience. J Rheumatol. 2006;33:854-861.
  2. Data on file, Amgen.
The PRESTA Study
Expand/Collapse

The PRESTA Study1:

Efficacy in psoriatic arthritis

  • A 24-week, randomized, multicenter, two-period study of 752 patients with active psoriatic arthritis (mean BSA of 30.82), consisting of a 12-week double-blind treatment period followed by a 12-week open-label treatment period
  • All patients had both psoriatic arthritis and moderate to severe chronic plaque psoriasis and were candidates for systemic therapy. Mean duration of psoriatic arthritis was 7.08 years and mean duration of plaque psoriasis was 18.92 years
  • The mITT population of 752 included all patients who received one dose of trial drug and had at least one postbaseline efficacy evaluation
    • The PRESTA study included a limited number of patients with zero painful and/or swollen joint counts at baseline, including 18 of the 373 in the 50 mg QW arm
  • At baseline, 36% of the mITT population (n = 752) had prior MTX use
    • During the trial, 25% of patients received concomitant MTX (mean weekly dose of 12.71 mg)
    • DMARDs and systemic antipsoriasis therapies other than MTX and acitretin were prohibited within 28 days before baseline until the end of the trial
  • Patients were randomized to receive ENBREL 50 mg BIW over the 12-week blinded treatment period followed by ENBREL 50 mg QW over the 12-week open-label treatment period (n = 379) or ENBREL 50 mg QW over both the 12-week blinded treatment period and the 12-week open-label treatment period (n = 373)
  • Subjects were evaluated at baseline and at Weeks 3, 6, 12, 18, and 24
  • The primary efficacy endpoint was the comparison between subjects in the ENBREL 50 mg BIW/QW group and the ENBREL 50 mg QW group for the proportion of subjects achieving a status of clear or almost clear on the Physician Global Assessment (PGA) of psoriasis at Week 12

References

  1. Data on file, Pfizer Inc.
The Psoriatic Arthritis Trial
Expand/Collapse

The Psoriatic Arthritis Pivotal Trial1-4:

  • Multicenter, double-blind, phase 3 trial of 205 patients with active psoriatic arthritis
  • Mean duration of arthritic disease was about 9.1 years and mean duration of plaque psoriasis was about 19.0 years (with a qualifying target skin lesion)
  • Patients were randomized to receive subcutaneous injections of ENBREL 25 mg (n = 101) or placebo (n = 104) administered twice weekly over the 24-week blinded treatment period
  • After the 24-week period, patients continued therapy in a maintenance period up to 6 months until all patients completed double-blind therapy. After the maintenance period, all patients received ENBREL 25 mg twice weekly in an open-label period of 48 weeks
  • The data were stratified by absence or presence of concurrent MTX (either ENBREL alone [n=59] vs placebo [n = 61] or ENBREL + MTX [n = 42] vs placebo + MTX [n = 43])
  • Stable use of corticosteroids and/or NSAIDs was allowed. Of the 205 patients in the blinded study, 169 patients (81 originally receiving placebo, 88 originally receiving ENBREL) entered the open-label extension. As actual timing for radiographs may have differed from the target time points, linear extrapolation was utilized to adjust for the radiographic data to the target time point
  • Nonresponder imputation analysis was conducted during the double-blind portion for ACR response and skin lesion clearing, while parameters assessed during the open-label period were analyzed based on the observed population at each time point
  • The primary radiographic endpoint was the annualized rate of change in TSS over 1 year of treatment
  • Secondary radiographic endpoints included annualized rate of change in TSS, erosion score, and joint space narrowing score at 6, 12, and 24 months
  • Radiographs of hands and wrists were taken at baseline and 6 months in the controlled portion of the trial, at initiation of open-label treatment, at 1 year and 2 years from original baseline, and at early termination from the study during either part of the study
  • All patients who received at least 1 dose of study drug and who had at least 1 radiograph were to be included in the radiographic analysis. Scores were adjusted to 6- or 12-month basis using linear interpolation/extrapolation of the observed change
  • The mean duration of ENBREL exposure during the 12-month radiographic period was 331.6 days in the ENBREL group and 27.6 days in the placebo group

Definition:

  • TSS is based on combined scores of joint erosions in the hands and wrists on a scale of 0 to 5 (0 = no damage) and joint space narrowing in the hands and wrists on a scale of 0 to 4 (0 = no narrowing) and was modified to include an assessment of the distal interphalangeal joints. Data are shown for all patients having a 2-year radiograph (n = 141)

References

  1. Enbrel® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
  2. Data on file, Amgen.
  3. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50:2264-2272.
  4. Mease PJ, Kivitz AJ, Burch FX, et al. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol. 2006;33:712-721.
The TEMPO Trial
Expand/Collapse

THE TEMPO Trial1-3:

  • Multicenter, double-blind, European, Australian, and Israeli trial of 682 patients with moderately to severely active RA (mean duration of disease: 7 years) who had an inadequate response to at least one prior DMARD but were not refractory to MTX
  • Patients were randomized to receive MTX monotherapy (n = 228), twice-weekly ENBREL 25 mg as monotherapy (n = 223), or twice-weekly ENBREL 25 mg in combination with MTX (n = 231)
    • All patients receiving MTX started at a dose of 7.5 mg/week whereby inadequate responders could be rapidly escalated up to 20 mg/week by Week 8
  • Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted. All data based on ITT, LOCF analysis except where otherwise noted
  • The primary clinical endpoint was the area under the curve (AUC) of the ACR numeric score at 24 weeks
  • The primary radiographic endpoint was the change from baseline in TSS at 12 months

References

  1. Enbrel® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
  2. Klareskog L, van der Heijde D, de Jager JP, et al, for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.
  3. Data on file, Amgen.

References

ACR. Slide Collection on the Rheumatic Diseases; 2004. Available at http://images.rheumatology.org/viewphoto.php?imageId=2862526. Accessed March 17, 2011.

ACR Subcommittee on RA Guidelines. Guidelines for the Management of Rheumatoid Arthritis. 2002 Update. Arthritis Rheum. 2002;46:328-346.

Altman RD. In: The Merck Manual of Diagnosis and Therapy (online version). http://www.merckmanuals.com/home/print/sec05/ch066/ch066b.html. Revised February 2008, Accessed January 30, 2011.

Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.

Benet LZ, Kroetz, DL, Sheiner LB. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, eds. Gilman AG, consulting ed. Goodman and Gillman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill Book Co; 1996:3-27.

Bennett DE, Courval JM, Onorato I, et al. Prevalence of tuberculosis infection in the United States population. The National Health and Nutrition Examination Survey, 1999-2000. Am J Respir Crit Care Med. 2008;177:348-355.

Cassidy JT. Juvenile rheumatoid arthritis. In: Harris ED Jr, et al, eds. Kelley's Textbook of Rheumatology. Volume 2. 2005:1579-1596.

Data on file, Amgen and Pfizer.

Data on file, Amgen.

Data on file, Pfizer, Inc.

Davis JC Jr, van der Heijde D, Braun J, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis. A randomized, controlled trial. Arthritis Rheum. 2003;48:3230-3236.

DUKORAL® (oral, inactivated travelers' diarrhea and cholera vaccine) Product Monograph. Toronto, Ontario, Canada: Sanofi Pasteur Limited; November 2007.

Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.

Emery P, Breedveld F, van der Heijde D, et al, for the Combination of Methotrexate and Etanercept in Early Rheumatoid Arthritis Trial Group. Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study. Arthritis Rheum. 2010;62:674-682. Erratum in: Arthritis Rheum. 2010;62:3005.

Enbrel® (etanercept) Medication Guide. Thousand Oaks, CA: Immunex Corporation; October 2010.

Enbrel® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; May 2011.

Genovese MC, Bathon JM, Fleischmann RM, et al. Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.

Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.

Gladman DD. Psoriatic arthritis. In: Isenberg DA, Maddison PJ, Woo P, Glass D, Breedveld FC, eds. Oxford Textbook of Rheumatology. 3rd ed. Oxford University Press; 2004.

Halbig M, Horneff G. Improvement of functional ability in children with juvenile idiopathic arthritis by treatment with etanercept [published online ahead of print May 16, 2009]. Rheumatol Int. doi:10.1007/s00296-009-0942-3. http://www.springer.com/medicine/rheumatology/journal/296. Accessed November 2, 2009.

Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford). 2003;42:1460-1468.

Klareskog L, van der Heijde D, de Jager JP, et al, for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.

Krishnan E, Sokka T, Häkkinen A, Hubert H, Hannonen P. Normative values for the Health Assessment Questionnaire disability index: benchmarking disability in the general population. Arthritis Rheum. 2004;50:953-60.

Krueger GG. Clinical features of psoriatic arthritis. Am J Manag Care. 2002;8:S160-S170.

Lipsky PE. Rheumatoid arthritis. In: Fauci AS, Braunweld E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser ST, Longo DL, Harrison TR, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Book Co; 2008:2083-2092.

Lovell DJ. Juvenile idiopathic arthritis. A. Clinical features. In: Klippel JH, et al. Primer on the Rheumatic Diseases. 13th ed. 2008:142-148.

McQueen FM, Stewart N, Crabbe J, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis. 1998;57:350-356.

Mease P, Goffe BS. Diagnosis and treatment of psoriatic arthritis. J Am Acad Dermatol. 2005;52:1-19.

Mease PJ, Kivitz AJ, Burch FX, et al. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol. 2006;33:712-721.

Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50:2264-2272.

Mease PJ. Cytokine blockers in psoriatic arthritis. Ann Rheum Dis. 2001;60 Suppl 3:iii37-iii40.

Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.

Moreland LW, Weinblatt ME, Keystone EC, et al. Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical experience. J Rheumatol. 2006;33:854-861.

National Psoriasis Foundation. Finding the right doctor. http://www.psoriasis.org/NetCommunity/Page.aspx?pid=395. Accessed January 30, 2011.

National Psoriasis Foundation. Treating psoriatic arthritis. http://www.psoriasis.org/NetCommunity/Page.aspx?pid=398. Accessed January 30, 2011.

National Psoriasis Foundation. Diagnosing Psoriatic Arthritis. http://psoriasis.org/netcommunity/learn_psadiagnosis. Accessed January 18, 2011

National Psoriasis Foundation. Psoriatic arthritis. http://psoriasis.org/netcommunity/psoriatic_arthritis. Accessed January 31, 2011.

Oates JA, Wilkinson GR. In: Fauci AS, Braunweld E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser ST, Longo DL, Harrison TR, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Book Co; 1998:411-412.

Okada SK, Siegel JN. Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis. JAMA. 2006;296:2201-2202; author reply 2203-2204.

Reich K, Krüger K, Mössner R, Augustin M. Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis. Br J Dermatol. 2009;160:1040-1047.

Saad AA, Symmons DP, Noyce PR, Ashcroft DM. Risks and benefits of tumor necrosis factor-alpha inhibitors in the management of psoriatic arthritis: systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2008;35:883-890.

Saag KG, Teng GG, Patkar NM, et al, for the American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59:762-784.

Salvarani C, Lo Scocco G, Macchioni P, et al. Prevalence of psoriatic arthritis in Italian psoriatic patients. J Rheumatol. 1995;22:1499-1503.

Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002;301:418-426.

Stedman's Medical Dictionary. 28th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.

Taurog JD. The spondyloarthritides. In: Fauci AS, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. 2008:2109-2119.

Tehlirian CV, Bathon JM. Rheumatoid arthritis. A. Clinical and laboratory manifestations. In: Klippel JH. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008:114-121.

TICE® BCG (for intravesical use) Prescribing Information. Durham, NC: Organon Teknika Corporation LLC; February 2009.

Torre Alonso JC, Rodriguez Perez A, Arribas Castrillo JM, Ballina Garcia J, Riestra Noriega JL, Lopez Larrea C. Psoriatic arthritis (PA): a clinical, immunological and radiological study of 180 patients. Br J Rheumatol. 1991;30:245-250.

Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.

Van der Heijde D. Ankylosing spondylitis. A. Clinical features. In: Klippel JH, et al. Primer on the Rheumatic Diseases. 13th ed. 2008:193-199.

Winchester R. Psoriatic arthritis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, eds. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: Mc-Graw Hill; 2008:194-207.



Important Safety Information Prescribing Information Medication Guide
Indications
 
Moderate to Severe Rheumatoid Arthritis Supportive Data Psoriatic Arthritis Supportive Data
Safety Information ISI

IN MODERATE TO SEVERE EARLY RA
Rapid and sustained improvement1

At 2 years, patients on ENBREL + MTX had sustained ACR 70 improvements.

View clinical efficacy

View in-depth ENBREL efficacy data from the COMET trial

Explore 3 measures of efficacy in moderate to severe RA with COMET Interactive.

Take a deeper look
Prescribing Information Medication Guide
 
 
Close
You are leaving Enbrel.com/RheumPro
Please know that Amgen and Pfizer do not endorse and are not responsible for the content included on the site you are about to enter. Click the "Continue" button to proceed.
Continue Cancel

To return to ENBREL.com, click "Cancel" or close this window.

Privacy Policy  Terms of Use
This site is intended for US Audiences only.
©2011 Amgen, Inc., Thousand Oaks, CA 91320 and Pfizer Inc
Close
E-mail this page to a colleague
Please correct the fields marked in red
Send
This content is for US health care professionals only. Amgen and Pfizer will not use your e-mail address or your colleague's e-mail address for any other purpose. To learn more about our use of your information and your rights, please consult our Privacy Policy.
Close

Send another e-mail
Return to enbrel.com/RheumPro

Close
Notice

The following information is intended for use only by residents of the United States. Countries outside of the United States may have regulatory requirements or medical practices that are different than those in the United States and may require reference to different or additional information. Therefore, this information may not be appropriate outside of the United States.

If you are a resident of the United States or one of its territories, or a health care professional practicing your profession in the United States or one of its territories, please click below.

Continue

If you are a resident of a country other than the United States, please visit the Pfizer website and the Amgen website to find information about our offices around the globe.
Close
Close
Disease activity vs. structural progression in RA