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

Completed

• Conditions: Rheumatoid Arthritis; Osteoporosis

• Registration Number: NCT01078155
• Lead Sponsor: AbbVie (prior sponsor, Abbott)

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2010-02-26
• Study First Submitted QC: 2010-02-26
• Study First Posted: 2010-03-02
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2015-05
• Results First Submitted: 2015-05-12
• Results First Submitted QC: 2015-05-12
• Results First Posted: 2015-05-29
• Last Update Submitted: 2015-05-29
• Last Update Posted: 2015-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 131

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Bone Turnover Marker C-telopeptide of Type I Collagen (CTX-I) From Baseline Through Month 3, Month 12, and Month 24	Baseline (Day 0), Month 3, Month 12, Month 24
Tender Joint Count at Baseline, Month 3, Month 12, and Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	The investigator counted the number of tender joints at each study visit (28 joints are routinely examined).
Bone Mineral Density (BMD) of Spine and Hip by Dual-energy X-ray Absorptiometry (DEXA) at Baseline, Month 12, and Month 24	Baseline (Day 0), Month 12, Month 24	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	Baseline (Day 0), Month 12, Month 24	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	Baseline (Day 0), Month 3, Month 12, Month 24
Mean Duration of Morning Stiffness at Baseline, Month 3, Month 12, and Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	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."
Change in Bone Turnover Marker C-terminal Type I Procollagen Peptide (CICP) From Baseline Through Month 3, Month 12, and Month 24	Baseline (Day 0), Month 3, Month 12, Month 24

Secondary Outcome Measures

Name	Time	Method
Visual Analogue Scale (VAS): Subject's Global Assessment of Disease Activity at Baseline, Month 3, Month 12, Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	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.
Swollen Joint Count at Baseline, Month 3, Month 12, and Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	The investigator counted the number of swollen joints at each study visit (28 joints are routinely examined).
Visual Analogue Scale (VAS): Physician's Global Assessment of Disease Activity at Baseline, Month 3, Month 12, Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	Physician's Global Assessment of Disease Activity VAS was reported on a 100 mm scale, where 0 = very good to 100 = very bad.
Erythrocyte Sedimentation Rate (ESR) at Baseline, Month 3, Month 12, Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	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.
Disease Activity Score in 28 Joints (DAS28) at Baseline, Month 3, Month 12, Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	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): Subject's Assessment of Pain at Baseline, Month 3, Month 12, Month 24	Baseline (Day 0), Month 3, Month 12, Month 24	Subject's Assessment of Pain VAS was reported on a 100 mm scale, where 0 = no pain through 100 = severe pain.