Evaluation of the Role of Adalimumab on Extraarticular Manifestation - Bone Metabolism and Bone Mineral Density in Patients With Active Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01078155
First received: February 26, 2010
Last updated: May 29, 2015
Last verified: May 2015
  Purpose

This post marketing observational study will be conducted in a prospective, single country, multicenter format to assess the prevention of generalized bone loss in patients with active rheumatoid arthritis (RA) treated with adalimumab (Humira®) in pragmatic prescribing situations. The investigational sites will be centers with experience in the treatment of RA patients and anti-tumor necrosis factor-alpha (TNF-a) therapy. The investigators will be rheumatologists authorized by the Czech Rheumatologic Society for prescribing biological treatment.


Condition
Rheumatoid Arthritis
Osteoporosis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Evaluation of the Role of Adalimumab on Extraarticular Manifestation - Bone Metabolism and Bone Mineral Density in Patients With Active Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Bone Mineral Density (BMD) of Spine and Hip by Dual-energy X-ray Absorptiometry (DEXA) at Baseline, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 12, Month 24 ] [ Designated as safety issue: No ]
    BMD of spine and hip (L1-L4 and proximal femur) by DEXA, evaluated according to standard clinical guidelines.

  • Spine and Hip T-score and Z-score by DEXA at Baseline, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 12, Month 24 ] [ Designated as safety issue: No ]
    T-score and Z-score of spine and hip (L1-L4 and proximal femur) by DEXA. T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 = normal bone density; < -1 and > -2.5 = a sign of osteopenia (bone density below normal); ≤ -2.5 = a sign of osteoporosis. Z-score is the number of standard deviations above or below what's normally expected for someone of matching age, sex, weight, and ethnic or racial origin. A Z-score ≤ -2 may suggest abnormal bone loss due to conditions other than aging.

  • Change in Bone Turnover Marker Osteocalcin (OC) From Baseline Through Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
  • Change in Bone Turnover Marker C-terminal Type I Procollagen Peptide (CICP) From Baseline Through Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
  • Change in Bone Turnover Marker C-telopeptide of Type I Collagen (CTX-I) From Baseline Through Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
  • Mean Duration of Morning Stiffness at Baseline, Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    Participant-reported the existence and duration of morning stiffness, defined as "morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement."

  • Tender Joint Count at Baseline, Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    The investigator counted the number of tender joints at each study visit (28 joints are routinely examined).


Secondary Outcome Measures:
  • Swollen Joint Count at Baseline, Month 3, Month 12, and Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    The investigator counted the number of swollen joints at each study visit (28 joints are routinely examined).

  • Disease Activity Score in 28 Joints (DAS28) at Baseline, Month 3, Month 12, Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    Scores on the DAS28 range from 0 to 10. DAS 28 ≥ 5.1= high RA disease activity; DAS 28 ≥ 3.2 = middle RA disease activity; DAS 28 ≤ 3.2 = lower disease activity; DAS 28 ≤ 2.6 = remission of disease.

  • Visual Analogue Scale (VAS): Physician's Global Assessment of Disease Activity at Baseline, Month 3, Month 12, Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    Physician's Global Assessment of Disease Activity VAS was reported on a 100 mm scale, where 0 = very good to 100 = very bad.

  • Visual Analogue Scale (VAS): Subject's Global Assessment of Disease Activity at Baseline, Month 3, Month 12, Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    Subject's Global Assessment of Disease Activity VAS was reported on a 100 mm scale, reporting the subject's evaluation of his/her difficulties as 0 = without any difficulty to 100 = significant difficulties.

  • Visual Analogue Scale (VAS): Subject's Assessment of Pain at Baseline, Month 3, Month 12, Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    Subject's Assessment of Pain VAS was reported on a 100 mm scale, where 0 = no pain through 100 = severe pain.

  • Erythrocyte Sedimentation Rate (ESR) at Baseline, Month 3, Month 12, Month 24 [ Time Frame: Baseline (Day 0), Month 3, Month 12, Month 24 ] [ Designated as safety issue: No ]
    ESR was recorded as per local clinical practice. Normal findings are up to 20 mm/hr for females and up to 15 mm/hr for males.


Biospecimen Retention:   Samples With DNA

osteocalcin (OC), C-terminal type I procollagen peptide (CICP), C-telopeptide of type I collagen (CTX-I), whole blood (serum)


Enrollment: 131
Study Start Date: March 2009
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Participants with Active Rheumatoid Arthritis (RA)
Participants (women and men) with active early and long-standing RA according to American College of Rheumatology revised criteria from 1987 were prescribed adalimumab in the usual manner in accordance with the terms of the local market authorization with regards to dose, population and indication as well as local guidelines. The decision to prescribe or not to prescribe an anti-TNF was taken prior to a participant's enrollment in the study.

  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

Patients with active rheumatoid arthritis

Criteria

Inclusion Criteria:

  • Patients with active early and long-standing RA according to American College of Rheumatology (ACR) 1987 revised criteria.
  • Patients with high disease activity DAS28 ≥ 5.1 according to the Czech Rheumatological Society criteria.
  • Patients must fulfill national guidelines for use of anti-TNF: inadequate clinical response to at least one disease-modifying antirheumatic drug (DMARD; methotrexate, sulphasalazine, leflunomide, hydroxychloroquine, or combinations) and oral glucocorticoids (equivalent to ≥ 5 mg prednisolone per day), (for Romania except glucocorticoids); chest X-ray, purified protein derivative (PPD)-skin test, Quantiferon/tuberculosis (TB) Gold test (if available) negative for TB.

Exclusion Criteria:

  • Patients who have had a history of TNF blocking or rituximab therapy.
  • Patients who are being treated or will be treated with drug at risk of interaction with adalimumab (Humira).
  • Pregnant females and/or females without adequate method of contraception.
  • Patients who didn't receive prior DMARD therapy.
  • Patients participating in another study or clinical trial.
  • Patients with severe osteoporosis (T-score [number that indicates whether or not bone loss has occurred] of ≤ -2.5 and/or prior vertebral fracture/s).
  • Patients with a history of total hip replacement of both extremities.
  • Patients who currently receive and/or received bone metabolism modulating agents including Selective Estrogen Receptor Modulators (SERMs), bisphosphonates, parathyroid hormone or anti-receptor activator of nuclear factor-kappaB ligand (RANKL) therapy.
  • Subjects who are not eligible for TNF-blocking therapy according to the Czech National Registry (ATTRA).
  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: NCT01078155

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Maroš Lipták, MD Abbvie, Czech Republic & Slovakia
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01078155     History of Changes
Other Study ID Numbers: P10-733
Study First Received: February 26, 2010
Results First Received: May 12, 2015
Last Updated: May 29, 2015
Health Authority: Romania: Ethics Committee
Romania: National Medicines Agency
Czech Republic: State Institute for Drug Control
Slovak Republic: Ethics Committee

Keywords provided by AbbVie:
Bone mineral density
Bone turnover markers
Rheumatoid arthritis
Osteoporosis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Osteoporosis
Autoimmune Diseases
Bone Diseases
Bone Diseases, Metabolic
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2015