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A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)

This study has been completed.
Sponsor:
Collaborator:
Pharma Consulting Group AB
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00808509
First received: December 12, 2008
Last updated: November 21, 2013
Last verified: November 2013
Results First Received: September 19, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label
Condition: Arthritis, Rheumatoid
Interventions: Biological: adalimumab
Drug: methotrexate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients with rheumatoid arthritis (RA) treated with adalimumab plus methotrexate and in remission for at least the past 3 months were enrolled from 8 investigative sites in Sweden.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized to continue or discontinue adalimumab treatment for 52 weeks. After the final visit an observational extension period ensued where patients were treated at the discretion of the investigator. The observational extension period lasted until a follow-up visit scheduled at Weeks 104 – 156 (average Week 125).

Reporting Groups
  Description
Adalimumab + MTX Participants continued treatment with adalimumab 40 mg subcutaneously every other week plus methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
Methotrexate Participants discontinued adalimumab and continued to receive methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. Participants with a significant increase in RA disease activity were re-instituted to adalimumab 40 mg every other week (rescue arm). After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.

Participant Flow for 2 periods

Period 1:   Randomized Phase
    Adalimumab + MTX     Methotrexate  
STARTED     17     16  
Received Rescue Therapy     0     9  
COMPLETED     15     11 [1]
NOT COMPLETED     2     5  
Did not meet eligibility criteria                 1                 0  
Reduced methotrexate dose                 1                 2  
Patient refused rescue therapy                 0                 3  
[1] Includes participants who received rescue therapy & follow-up for 12 weeks

Period 2:   Observation Phase
    Adalimumab + MTX     Methotrexate  
STARTED     16 [1]   15 [1]
COMPLETED     16     15  
NOT COMPLETED     0     0  
[1] The observation phase was open to all participants



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Adalimumab + MTX Participants continued treatment with adalimumab 40 mg subcutaneously every other week plus methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
Methotrexate Participants discontinued adalimumab and continued to receive methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. Participants with a significant increase in RA disease activity were re-instituted to adalimumab 40 mg every other week (rescue arm). After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
Total Total of all reporting groups

Baseline Measures
    Adalimumab + MTX     Methotrexate     Total  
Number of Participants  
[units: participants]
  17     16     33  
Age  
[units: years]
Mean ± Standard Deviation
  52.5  ± 13.0     61.3  ± 9.9     56.8  ± 12.2  
Gender  
[units: participants]
     
Female     11     11     22  
Male     6     5     11  
Region of Enrollment  
[units: participants]
     
Sweden     17     16     33  
Disease duration  
[units: years]
Mean ± Standard Deviation
  10.4  ± 8.9     13.2  ± 12.5     11.7  ± 10.7  
Disease Activity Score (DAS) 28 [1]
[units: units on a scale]
Mean ± Standard Deviation
  1.98  ± 0.48     1.73  ± 0.61     1.86  ± 0.55  
[1] The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants in Remission at Week 28   [ Time Frame: Week 28 ]

2.  Primary:   Percentage of Participants in Remission at Week 28 in the Full Analysis Set 2 (FAS2)   [ Time Frame: Week 28 ]

3.  Secondary:   Percentage of Participants in Remission at Week 52   [ Time Frame: Week 52 ]

4.  Secondary:   Percentage of Participants in Remission at Week 52 (FAS2)   [ Time Frame: Week 52 ]

5.  Secondary:   Number of Participants With a Flare   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52 ]

6.  Secondary:   Percentage of Participants With Response to Adalimumab Treatment (Return to Baseline DAS28 + ≤ 10%) After a Flare   [ Time Frame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy ]

7.  Secondary:   Percentage of Participants With Response to Adalimumab Treatment (DAS28 <2.6 or DAS28 Decrease >1.2 Units) After a Flare   [ Time Frame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy ]

8.  Secondary:   Health Assessment Questionnaire (HAQ) Total Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

9.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Mobility Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

10.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Self-care Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

11.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

12.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

13.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

14.  Secondary:   European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

15.  Secondary:   Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale by Visit   [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ]

16.  Secondary:   Work Instability Score (WIS) for RA: I'm Getting up Earlier Because of Arthritis   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

17.  Secondary:   Work Instability Score (WIS) for RA: I Get Very Stiff at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

18.  Secondary:   Work Instability Score (WIS) for RA: I'm Finding my Job is About All I Can Manage   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

19.  Secondary:   Work Instability Score (WIS) for RA: The Stress of my Job Makes my Arthritis Flare   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

20.  Secondary:   Work Instability Score (WIS) for RA: I'm Finding Any Pressure on my Hands is a Problem   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

21.  Secondary:   Work Instability Score (WIS) for RA: I Get Good Days and Bad Days at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

22.  Secondary:   Work Instability Score (WIS) for RA: I Can Get my Job Done, I'm Just a Lot Slower   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

23.  Secondary:   Work Instability Score (WIS) for RA: If I Don't Reduce my Hours I May Have to Give up Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

24.  Secondary:   Work Instability Score (WIS) for RA: I am Very Worried About my Ability to Keep Working   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

25.  Secondary:   Work Instability Score (WIS) for RA: I Have Pain or Stiffness All the Time at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

26.  Secondary:   Work Instability Score (WIS) for RA: I Don't Have the Stamina to Work Like I Used to   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

27.  Secondary:   Work Instability Score (WIS) for RA: I Have Used my Vacation so That I Don't Have to Take Sick Leave   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

28.  Secondary:   Work Instability Score (WIS) for RA: I Push Myself to go to Work Because I Don't Want to Give in to the Arthritis   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

29.  Secondary:   Work Instability Score (WIS) for RA: Sometimes I Can't Face Being at Work All Day   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

30.  Secondary:   Work Instability Score (WIS) for RA: I Have to Say No to Certain Things at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

31.  Secondary:   Work Instability Score (WIS) for RA: I've Got to Watch How Much I do Certain Things at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

32.  Secondary:   Work Instability Score (WIS) for RA: I Have Great Difficulty Opening Some of the Doors at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

33.  Secondary:   Work Instability Score (WIS) for RA: I Have to Allow Myself Extra Time to do Some Jobs   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

34.  Secondary:   Work Instability Score (WIS) for RA: It's Very Frustrating Because I Can't Always do Things at Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

35.  Secondary:   Work Instability Score (WIS) for RA: I Feel I May Have to Give up Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

36.  Secondary:   Work Instability Score (WIS) for RA: I Get on With the Work But Afterwards I Have a Lot of Pain   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

37.  Secondary:   Work Instability Score (WIS) for RA: When I'm Feeling Tired All the Time Work is a Grind   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

38.  Secondary:   Work Instability Score (WIS) for RA: I'd Like Another Job But I am Restricted to What I Can do   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

39.  Secondary:   Work Productivity and Activity Impairment (WPAI): Currently Employed   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

40.  Secondary:   Work Productivity and Activity Impairment (WPAI): Hours Missed From Work   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

41.  Secondary:   Work Productivity and Activity Impairment (WPAI): Hours Missed From Work for Other Reasons   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

42.  Secondary:   Work Productivity and Activity Impairment (WPAI): Hours Worked   [ Time Frame: Baseline and at Weeks 12, 28, 52 and 104-156 ]

43.  Secondary:   Work Productivity and Activity Impairment (WPAI): Work Productivity   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

44.  Secondary:   Work Productivity and Activity Impairment (WPAI): Daily Activities   [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ]

45.  Secondary:   Change From Baseline in Radiological Modified Total Sharp Score   [ Time Frame: Baseline, Week 52, and Weeks 104-156 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Global Medical Services
Organization: AbbVie (prior sponsor, Abbott)
phone: 800-633-9110


No publications provided


Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00808509     History of Changes
Other Study ID Numbers: W10-046, 2008-004398-16
Study First Received: December 12, 2008
Results First Received: September 19, 2013
Last Updated: November 21, 2013
Health Authority: Sweden: Medical Products Agency