Efficacy and Safety of Adalimumab in Subjects With Moderate to Severe Chronic Plaque Psoriasis

A Multicenter Open-Label Continuation Study in Moderate to Severe Chronic Plaque Psoriasis Subjects Who Completed a Preceding Psoriasis Clinical Study With Adalimumab

The two objectives of this study were to evaluate long-term efficacy and safety of adalimumab treatment in participants who had moderate to severe chronic plaque psoriasis and to evaluate the effectiveness of adalimumab retreatment in participants who had therapeutic response to adalimumab and were then withdrawn from adalimumab treatment.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: adalimumab

Detailed Description

Study M03-658 was a continuation study for participants with moderate to severe psoriasis who had participated in a prior psoriasis adalimumab study. Study M03-658 consisted of three sequential treatment periods. The first period was Period O, in which participants received open-label treatment with adalimumab (40 mg every other week or 40 mg every week) for a minimum of 104 weeks and a maximum of 252 weeks. Period O was the only period of the study until May 2008, when the subsequent periods were added via amendment to the protocol. At that time, participants who had achieved satisfactory therapeutic response (a Physician's Global Assessment [PGA] of 0, 1, or 2 [clear, minimal, or mild]) were given the opportunity to discontinue from the study or to continue and participate in the subsequent two periods. The second period was Period W, a maximum of 52 weeks, in which participants with a PGA of 2 (mild) or less were withdrawn from adalimumab treatment (i.e., participants received no treatment) until relapse of their psoriasis occurred (defined as a PGA of 3 [moderate] or worse). The third period was Period R, a 16-week period in which participants were retreated with open-label adalimumab (80 mg initial dose followed by 40 mg every other week). Period O was designed to evaluate the first objective regarding long-term efficacy and safety of adalimumab treatment, and Period R was designed to evaluate the effectiveness of adalimumab retreatment following relapse. Specific subsets of the study population that were identified as the populations of interest were the modified intent-to-treat populations for Period W and Period R, and these are described further in the outcome measures.

• Study Type: Interventional
• Enrollment (Actual): 1469
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Site Reference ID/Investigator# 2181
  • Innsbruck, Austria, A-6020
    • Site Reference ID/Investigator# 2180
  • Vienna, Austria, 1090
    • Site Reference ID/Investigator# 2176
• Belgium
  • Brussels, Belgium, 1200
    • Site Reference ID/Investigator# 2554
  • Edegem, Belgium, 2650
    • Site Reference ID/Investigator# 2179
• Canada
  • Quebec, Canada, G1V 4X7
    • Site Reference ID/Investigator# 1802
  • Alberta
    • Calgary, Alberta, Canada, T2S 3B3
      • Site Reference ID/Investigator# 1629
    • Edmonton, Alberta, Canada, T5K 1X3
      • Site Reference ID/Investigator#1641
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • Site Reference ID/Investigator# 104
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 4S8
      • Site Reference ID/Investigator# 1635
    • St. John's, Newfoundland and Labrador, Canada, A1C 2H5
      • Site Reference ID/Investigator# 120
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1Z4
      • Site Reference ID/Investigator# 94
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1V6
      • Site Reference ID/Investigator# 1640
    • London, Ontario, Canada, N5X 2P1
      • Site Reference ID/Investigator# 1636
    • North Bay, Ontario, Canada, P1B 3Z7
      • Site Reference ID/Investigator# 1639
    • Toronto, Ontario, Canada, M5V 2T3
      • Site Reference ID/Investigator# 1633
    • Waterloo, Ontario, Canada, N2J 1C4
      • Site Reference ID/Investigator# 1631
    • Windsor, Ontario, Canada, N8W 1E6
      • Site Reference ID/Investigator# 103
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Site Reference ID/Investigator# 102
    • Montreal, Quebec, Canada, H2K 4L5
      • Site Reference ID/Investigator# 1637
    • Montreal, Quebec, Canada, H3H 1V4
      • Site Reference ID/Investigator# 101
    • Westmount, Quebec, Canada, H3Z 2S6
      • Site Reference ID/Investigator# 1647
• France
  • Creteil, France, 94010
    • Site Reference ID/Investigator# 2553
  • Nice, France, 06200
    • Site Reference ID/Investigator# 2191
  • Paris, Cedex 10, France, 75475
    • Site Reference ID/Investigator# 2190
  • Saint Etienne, France, 42055
    • Site Reference ID/Investigator# 2189
• Germany
  • Frankfurt, Germany, 60590
    • Site Reference ID/Investigator# 2198
  • Kiel, Germany, 24105
    • Site Reference ID/Investigator# 2543
  • Muenster, Germany, 48149
    • Site Reference ID/Investigator# 2188
  • Tuebingen, Germany, 72076
    • Site Reference ID/Investigator# 2187
• Poland
  • Gdansk, Poland, 80-211
    • Site Reference ID/Investigator# 2178
  • Plock, Poland, 09-402
    • Site Reference ID/Investigator# 2177
• Puerto Rico
  • Cagaus, Puerto Rico, 00725
    • Site Reference ID/Investigator# 2194
  • Carolina, Puerto Rico, 00985
    • Site Reference ID/Investigator# 5507
• Spain
  • Madrid, Spain, 28006
    • Site Reference ID/Investigator# 2182
  • Seville, Spain, 41009
    • Site Reference ID/Investigator# 2185
  • Valencia, Spain, 46014
    • Site Reference ID/Investigator# 2183
• Switzerland
  • Geneva 14, Switzerland, 1211
    • Site Reference ID/Investigator# 2193
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Site Reference ID/Investigator# 1263
    • Buckner 13075 PI, Alabama, United States, 35233
      • Site Reference ID/Investigator# 1259
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Site Reference ID/Investigator# 2427
    • Tucson, Arizona, United States, 85710
      • Site Reference ID/Investigator# 2433
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Site Reference ID/Investigator# 100
  • California
    • Bakersfield, California, United States, 93309
      • Site Reference ID/Investigator# 1798
    • Fresno, California, United States, 93720
      • Site Reference ID/Investigator# 122
    • Irvine, California, United States, 92697
      • Site Reference ID/Investigator# 1669
    • Oceanside, California, United States, 92056
      • Site Reference ID/Investigator# 1285
    • San Diego, California, United States, 92123
      • Site Reference ID/Investigator# 86
    • Santa Monica, California, United States, 90404
      • Site Reference ID/Investigator# 1679
    • Torrance, California, United States, 90503
      • Site Reference ID/Investigator# 1677
  • Colorado
    • Longmont, Colorado, United States, 80501
      • Site Reference ID/Investigator# 1269
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Site Reference ID/Investigator# 1275
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Site Reference ID/Investigator# 96
    • Pinellas Park, Florida, United States, 33781
      • Site Reference ID/Investigator# 2431
    • South Miami, Florida, United States, 33143
      • Site Reference ID/Investigator# 1273
    • West Palm Beach, Florida, United States, 33407
      • Site Reference ID/Investigator# 2432
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Site Reference ID/Investigator# 98
    • Newnan, Georgia, United States, 30263
      • Site Reference ID/Investigator# 1674
    • Snellville, Georgia, United States, 30078
      • Site Reference ID/Investigator# 1670
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site Reference ID/Investigator# 1264
    • Maywood, Illinois, United States, 60153
      • Site Reference ID/Investigator# 1801
    • Springfield, Illinois, United States, 62702
      • Site Reference ID/Investigator# 1681
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Site Reference ID/Investigator# 1267
    • Indianapolis, Indiana, United States, 46260
      • Site Reference ID/Investigator# 1671
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Site Reference ID/Investigator# 1258
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Site Reference ID/Investigator# 1281
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Site Reference ID/Investigator# 1668
    • Boston, Massachusetts, United States, 02114
      • Site Reference ID/Investigator# 1683
    • Worcester, Massachusetts, United States, 01610
      • Site Reference ID/Investigator# 83
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Site Reference ID/Investigator# 93
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Site Reference ID/Investigator# 92
    • Minneapolis, Minnesota, United States, 55455
      • Site Reference ID/Investigator# 1262
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Site Reference ID/Investigator# 1657
    • St. Louis, Missouri, United States, 63117
      • Site Reference ID/Investigator# 89
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Site Reference ID/Investigator# 1673
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Site Reference ID/Investigator# 2119
  • New York
    • New York, New York, United States, 10016
      • Site Reference ID/Investigator# 1672
    • New York, New York, United States, 10025
      • Site Reference ID/Investigator# 1797
    • New York, New York, United States, 10029
      • Site Reference ID/Investigator# 95
    • New York, New York, United States, 10032
      • Site Reference ID/Investigator# 1655
    • Rochester, New York, United States, 14623
      • Site Reference ID/Investigator# 88
    • Williamsville, New York, United States, 14221
      • Site Reference ID/Investigator# 1256
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Site Reference ID/Investigator# 1266
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Site Reference ID/Investigator# 1265
    • Cleveland, Ohio, United States, 44106
      • Site Reference ID/Investigator# 90
    • Columbus, Ohio, United States, 43212
      • Site Reference ID/Investigator# 2434
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Site Reference ID/Investigator# 1260
    • Portland, Oregon, United States, 97210
      • Site Reference ID/Investigator# 1667
    • Portland, Oregon, United States, 97223
      • Site Reference ID/Investigator# 121
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Site Reference ID/Investigator# 1323
    • Philadelphia, Pennsylvania, United States, 19103
      • Site Reference ID/Investigator# 1277
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Site Reference ID/Investigator# 99
    • Providence, Rhode Island, United States, 02903
      • Site Reference ID/Investigator# 1676
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Site Reference ID/Investigator# 97
    • Mount Pleasant, South Carolina, United States, 29464
      • Site Reference ID/Investigator# 5199
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Site Reference ID/Investigator# 1800
    • Nashville, Tennessee, United States, 37215
      • Site Reference ID/Investigator# 1282
  • Texas
    • Dallas, Texas, United States, 75246-1613
      • Site Reference ID/Investigator# 87
    • Houston, Texas, United States, 77030
      • Site Reference ID/Investigator# 1279
    • San Antonio, Texas, United States, 78229
      • Site Reference ID/Investigator# 1665
    • Tyler, Texas, United States, 75703
      • Site Reference ID/Investigator# 1268
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Site Reference ID/Investigator# 2079
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Site Reference ID/Investigator# 123
  • Washington
    • Seattle, Washington, United States, 98101
      • Site Reference ID/Investigator# 1653

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
• Subjects who met the requirements from previous adalimumab psoriasis study participation.

Exclusion Criteria:

• Subject considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
• Female subject who was pregnant or breast-feeding or considering becoming pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Adalimumab	Drug: adalimumab; 40 mg every other week or 40 mg every week by subcutaneous injection; Other Names: ABT-D2E7; Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R	The Physician's Global Assessment [PGA] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.	Week 16 of Period R

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 60	The Physician's Global Assessment [PGA] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.	Week 60
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 120	The Physician's Global Assessment [PGA] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.	Week 120
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 60	Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study.	Week 60
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 120	Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study.	Week 120
Time to Relapse in Period W	Relapse of psoriasis was defined as a Physician's Global Assessment (assessment of overall lesion severity) score of greater than or equal to 3 (3=moderate; 4=severe; 5=very severe).	Period W
Percentage of Period R Modified Intent-to-Treat Participants Who Relapsed in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R	The Physician's Global Assessment [PGA] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.	Week 16 of Period R
Percentage of Period R Modified Intent-to-Treat Participants Who Did Not Relapse in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R	The Physician's Global Assessment [PGA] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.	Week 16 of Period R

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Martin Okun, MD, PhD, Abbott

Publications and helpful links

General Publications

• Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012 Feb;66(2):241-51. doi: 10.1016/j.jaad.2010.12.005. Epub 2011 Jul 14.
• Papp K, Crowley J, Ortonne JP, Leu J, Okun M, Gupta SR, Gu Y, Langley RG. Adalimumab for moderate to severe chronic plaque psoriasis: efficacy and safety of retreatment and disease recurrence following withdrawal from therapy. Br J Dermatol. 2011 Feb;164(2):434-41. doi: 10.1111/j.1365-2133.2010.10139.x.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): April 13, 2011
• Last Update Submitted That Met QC Criteria: April 11, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M03-658; 2005-000095-41 (EudraCT Number)