A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate

• Psoriasis Area and Severity Index (PASI) 75 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PASI 75 response, standard dose versus MTX.
• Physician's Global Assessment of Disease Activity (PGA) 0, 1 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PGA 0, 1 standard dose versus MTX.
• Adverse Events [ Time Frame: At every visit from Baseline (Week 0) to final Visit (Week 156) ] [ Designated as safety issue: Yes ]
  Any untoward medical occurrence

• Psoriasis Area and Severity Index (PASI) 75 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a >= PASI 75 response, standard dose versus MTX
• Physician's Global Assessment of Disease Activity 0, 1 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PGA 0, 1 standard dose versus MTX.
• Adverse Events [ Time Frame: At every visit from Baseline (Week 0) to final Visit (Week 156) ] [ Designated as safety issue: Yes ]
  Any untoward medical occurrence

• Psoriasis Area and Severity Index (PASI) 90 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PASI 90, standard dose versus MTX
• Psoriasis Area and Severity Index (PASI) 100 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PASI 90, standard dose versus MTX
• Children's Dermatology Life Quality Index [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  Change from baseline in the Children's Dermatology Life Quality Index (CDLQI) scores, standard dose versus MTX
• Change from baseline in the Paediatric Quality of Life Inventory [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  Change from baseline in the Paediatric Quality of Life Inventory (PedsQL), standard dose versus MTX
• Physician's Global Assessment of Disease Activity 0,1 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving PGA 0, 1 upon completion of retreatment (Period C) according to the original randomised group assignment in Period A (standard dose adalimumab versus low dose adalimumab)
• Time to Loss of Disease Control [ Time Frame: Time from entry into Period B until loss of disease control ] [ Designated as safety issue: No ]
  Time to loss of disease control (Period B) according to the original randomised group assignment in Period A (standard dose adalimumab versus low dose adalimumab and MTX)

• Psoriasis Area and Severity Index (PASI) 90 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PASI 90, standard dose versus MTX
• Psoriasis Area and Severity Index (PASI) 100 [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  The proportion of subjects achieving a PASI 90, standard dose versus MTX
• Children's Dermatology Life Quality Index [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  Change from baseline in the Children's Dermatology Life Quality Index (CDLQI) scores, standard dose versus MTX
• Change from baseline in the Paediatric Quality of Life Inventory [ Time Frame: Week 16, Period A ] [ Designated as safety issue: No ]
  Change from baseline in the Paediatric Quality of Life Inventory (PedsQL), standard dose versus MTX
• Physician's Global Assessment (PGA) of Disease Activity 0,1 [ Time Frame: Week 16, Period C ] [ Designated as safety issue: No ]
  The proportion of subjects achieving PGA 0, 1 upon completion of retreatment (Period C) according to the original randomised group assignment in Period A (standard dose adalimumab versus low dose adalimumab)
• Time to Loss of Disease Control [ Time Frame: Not defined ] [ Designated as safety issue: No ]
  Time to loss of disease control (Period B) according to the original randomised group assignment in Period A (standard dose adalimumab versus low dose adalimumab and MTX).

This study will compare how well adalimumab works versus methotrexate (MTX) in children with moderate to severe psoriasis in the short term. It will also study how safe and how well adalimumab works in the long term and how long disease response can be maintained after stopping therapy.

• Biological: Adalimumab - Low Dose
  0.4 mg/kg up to a maximum of 20mg every other week
  Other Name: ABT-D2E7 Humira
• Biological: Adalimumab - Standard Dose
  0.8 mg/kg up to a maximum of 40mg every other week
  Other Name: ABT-D2E7 Humira
• Drug: Methotrexate
  0.4mg/kg/week up to a maximum of 25 mg per week
• Biological: Adalimumab - Open-Label
  0.4 mg/kg up to a maximum of 20 mg every other week or 0.8 mg/kg up to a maximum of 40mg every other week starting at Week 0 in Open-Label Period
  Other Name: ABT-D2E7 Humira

• Experimental: Adalimumab - Low Dose
  Intervention: Biological: Adalimumab - Low Dose
• Experimental: Adalimumab - Standard Dose
  Intervention: Biological: Adalimumab - Standard Dose
• Active Comparator: Methotrexate
  Intervention: Drug: Methotrexate
• Experimental: Adalimumab Open-Label
  Intervention: Biological: Adalimumab - Open-Label

Inclusion Criteria:

1. Subject is ≥ 4 years and < 18 years of age;
2. Subject weighs ≥ 13 kg;
3. Subject must have failed to respond to topical therapy;

4. Subject must need systemic treatment to control his/her disease and meet one of the following:

   • Physician's Global Assessment (PGA) ≥ 4
   • Body surface area (BSA) involved > 20%
   • Very thick lesions with BSA > 10% - Psoriasis Area and Severity Index (PASI) > 20

   • PASI > 10 and at least one of the following:

     • Active psoriatic arthritis unresponsive to non-steroid anti-inflammatory drugs (NSAIDs)
     • Clinically relevant facial involvement
     • Clinically relevant genital involvement * Clinically relevant hand and/or foot involvement
     • Children's Dermatology Life Quality Index (CDLQI) > 10
5. If subject is < 12 years of age and resides in a geographic region where heliotherapy is practical, subject must have failed to respond, be intolerant, or have a contraindication to heliotherapy, or is not a suitable candidate for heliotherapy;
6. If ≥12 years of age, subject must have failed to respond, be intolerant, or have a contraindication to phototherapy, or is not a suitable candidate for phototherapy;
7. Subject must have a clinical diagnosis of psoriasis for at least 6 months as determined by the subject's medical history and confirmation of diagnosis through physical examination by the Investigator; 8. Subject must have stable plaque psoriasis for at least 2 months prior to Baseline

Exclusion Criteria:

1. Prior biologic use other than prior treatment with etanercept;
2. Treatment with etanercept therapy within 4 weeks prior to the Baseline visit;
3. Methotrexate (MTX) use within the past year or prior MTX use at any time where the subject did not respond, or did not tolerate MTX;
4. Contraindication for treatment with MTX during the study;
5. Erythrodermic Ps, generalized or localized pustular Ps, medication-induced or medication exacerbated Ps or new onset guttate Ps;
6. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit;
7. Treatment of Ps with topical therapies such as corticosteroids, vitamin D analogs, or retinoids within 7 days prior to the Baseline visit;
8. Treatment of Ps with UVB phototherapy, excessive sun exposure, or the use of tanning beds within 7 days prior to the Baseline visit;
9. Treatment of Ps with PUVA phototherapy, non-biologic systemic therapies for the treatment of Ps, or systemic therapies known to improve Ps within 14 days prior to the Baseline visit;