Basic Documentation of Adalimumab (Humira) in Patients With Ankylosing Spondylitis (AS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01079182
First received: March 1, 2010
Last updated: June 10, 2015
Last verified: June 2015
  Purpose

The research question explored in this study was whether the effectiveness and safety of adalimumab in participants with ankylosing spondylitis was maintained during long-term therapy in routine clinical practice in Germany.


Condition
Ankylosing Spondylitis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Safety and Effectiveness of Adalimumab in Patients With Ankylosing Spondylitis in Routine Clinical Practice

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    The BASDAI was a six question, participant-reported measure of overall disease activity that probed the level of fatigue, neck/back/hip pain, peripheral joint swelling and pain, localized tenderness, as well as morning stiffness severity and duration. It was scored on a numerical rating scale that ranged from 0 (no symptoms) to 10 (severe symptoms), and the minimum clinically important difference (MCID) was 1.0. The final BASDAI score was calculated using the following equation, in which 01 - 06 represents the question number: (BASDAI01 + BASDAI02 + BASDAI03 + BASDAI04 + BASDAI05/2 + BASDAI06*1.25/2)/5. The scale for question 6 was reduced to 0-8 since BASDAI06 was multiplied by 1.25. Data are reported as the mean change total score from baseline (Month 0).

  • Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    The BASFI was a ten question, participant-reported measure that evaluated physical function. Each question was scored on a numerical rating scale that ranged from 0 (no functional impairment) to 10 (maximal impairment), and the MCID was 0.7. The mean of the ten questions was the total BASFI score. Data are reported as the mean change of total score from baseline (Month 0).

  • Number of Participants With Drug-Related Adverse Events (AEs) [ Time Frame: From signing of informed consent up to 24 months ] [ Designated as safety issue: Yes ]
    An adverse event/adverse experience was any reaction, side effect or other untoward event associated with the use of a drug in humans, whether or not the event was considered drug related. This included adverse events occurring from accidental or deliberate drug overdose, from drug abuse, or from drug withdrawal. Exacerbations of pre-existing conditions are also considered adverse events. Data presented are adverse events that are drug-related and are detailed in the adverse event section of this report.


Secondary Outcome Measures:
  • Mean Number of Involved Peripheral Joints [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Peripheral joints were assessed by Tender Joint Counts (TJC) and Swollen Joint Counts (SJC), using pressure and joint manipulation during physical examination. Seventy-eight TJC and 76 SJC were evaluated and a score of 0 (not tender or swollen) or 1 (tender or swollen) was assigned for each joint with a higher total score indicating a greater number of involved joints.

  • Percentage of Participants With Extraspinal Manifestations [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Extraspinal manifestations (enthesitis, dactylitis, uveitis, psoriasis, and Inflammatory Bowel Disease (IBD)) were assessed by investigators and reported on the basis of their clinical evaluation and participant records.

  • Mean Erythrocyte Sedimentation Rate (ESR) [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Plasma concentrations of ESR were assessed as a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies.

  • Mean Plasma Concentrations of C-Reactive Protein (CRP) [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Plasma concentrations of CRP were assessed as a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies.

  • Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    The BAS-G was a participant-reported instrument with two items. In the first item, the participant rated the effect of their disease over the last week, and in the second item, the participant rated the effect of their disease over the previous 6 months. Each item of the BAS-G was scored on a scale ranging from 0 (no effect) to 10 (very severe effect). The mean of the two scores was the total BAS-G score and the MCID was 1.5.

  • Mean Global Assessment of Disease Activity Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Global Assessment of Disease Activity was a participant-reported measure that evaluated disease activity. It was scored on a scale that ranged from 0 to 10; lower scores indicated better patient status.

  • Mean Participant Fatigue Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Using the BASDAI questionnaire, participants assessed the overall level of fatigue/tiredness experienced by him/her. It was scored on a numerical rating scale from 0 (no symptoms) to 10 (severe symptoms).

  • Mean Participant Pain Score [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Using the BASDAI questionnaire, participants assessed the overall level of AS neck, back or hip pain experienced by him/her. It was scored on a numerical rating scale from 0 (no symptoms) to 10 (severe symptoms).

  • Percentage of Participants With Morning Stiffness [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Morning stiffness was a participant-reported assessment. The number of participants with morning stiffness were assessed at each visit.

  • Mean Duration of Morning Stiffness [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Participants accessed the duration of morning stiffness in 15 minute intervals from 0 to 2 hours. Data are reported as the mean duration of morning stiffness ± standard deviation.

  • Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria [ Time Frame: At 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    This is a four domain (participant global assessment of disease activity, assessment of spinal pain, assessment of function (BASFI), and assessment of duration/severity of morning stiffness (mean of BASDAI questions 5 and 6)), participant-reported assessment scored on a scale from 0 (best) to 10 (worst). To qualify for a 20% improvement, participants were required to have an improvement of greater than or equal to 20% and greater than or equal to 1 unit in at least 3 domains, and no worsening of greater than or equal to 20% and greater than or equal to 1 unit in the remaining domain. To achieve a 40% improvement, participants were required to have an improvement of greater than or equal to 40% and greater than or equal to 2 units in at least 3 domains, and no worsening at all in the remaining domain.

  • Percentage of Participants Achieving ASAS Partial Remission Criteria [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    This is a four domain (participant global assessment of disease activity, assessment of spinal pain, assessment of function (BASFI), and assessment of duration/severity of morning stiffness (mean of BASDAI questions 5 and 6)), participant-reported assessment scored on a scale from 0 (best) to 10 (worst). To qualify for a partial remission, participants had to have values of 2 or less (on a scale of 10) in each of the 4 domains.

  • Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    The impairment of daily activities was based on participant recall of events that occurred over the 4 weeks before the visit. Percentage of participants with impairment for 0, less than 7, 7 to 14, and greater than 14 days was assessed.

  • Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Percentage of Participants on Adalimumab Monotherapy [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    Participants with concomitant pain relief/anti-inflammatory agents like analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, and systemic glucocorticoids were assessed during the study period.

  • Mean Equivalent Dose of Prednisolone [ Time Frame: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]
    The mean equivalent dose of prednisolone was calculated based on the International Standard for comparison of different glucocorticoid products.


Enrollment: 4681
Study Start Date: January 2006
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Ankylosing spondylitis
Participants with ankylosing spondylitis

Detailed Description:

This was a postmarketing observational study (PMOS) for participants with insufficiently controlled, moderate to severe, active AS who were eligible for adalimumab therapy. Participants started treatment with adalimumab under normal clinical settings in Germany. Enrolled participants were followed during adalimumab therapy . Participants were assessed during regular clinic visits for up to 24 months and 359 clinicians (rheumatologists/orthopedists/general practitioners/internist) participated in the study. Since this was an observational trial, not all doctors followed the stated age limitations and some participants under the age of 18 were enrolled.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participants with AS in routine clinical practice.

Criteria

Inclusion Criteria:

  1. Participants with active, AS for at least 4 weeks (BASDAI greater than or equal to 4).
  2. Participants who failed treatment with two non-steroidal anti-inflammatory drugs (NSAIDs).
  3. No contraindications for anti-tumor necrosis factors (TNF) therapy.

Exclusion Criteria:

1. Participants who do not meet the above listed inclusion criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079182

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Bianca Wittig, MD AbbVie Deutschland GmbH & Co. KG, Medical Department
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01079182     History of Changes
Other Study ID Numbers: P10-147
Study First Received: March 1, 2010
Results First Received: May 13, 2015
Last Updated: June 10, 2015
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by AbbVie:
Daily practice
Humira
Efficacy
Safety
Ankylosing spondylitis

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Ankylosis
Arthritis
Bone Diseases
Bone Diseases, Infectious
Infection
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthritis
Spondylarthropathies

ClinicalTrials.gov processed this record on August 26, 2015