ENBREL Safety Profile in Psoriatic Arthritis

The Psoriatic Arthritis Pivotal Trial^1-4:

• 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 PRESTA Study¹:

• 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.