Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab
Overview
- Phase
- Phase 4
- Intervention
- Tocilizumab
- Conditions
- Rheumatoid Arthritis
- Sponsor
- University of California, Los Angeles
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this research study is to determine if a change in inflammation or baseline inflammation seen on the ultrasound is a good indicator of how rheumatoid arthritis patients respond to TCZ 4mg/kg and whether early prediction of dose escalation is possible by utilizing ultrasound inflammatory measures.
Detailed Description
This is a 24-week, double blind open label clinical trial study to evaluate 57 active Rheumatoid Arthritis (RA) patients who have moderate to severe disease activity with total Power Doppler Ultrasound (PDUS) \>10 of 34 joints evaluated by Ultrasound (US) (at screening to enter into the study). All patients will begin treatment with tocilizumab at a dose of 4mg/kg. Two study sites will recruit patients (UCLA and UF) using the same protocol, after standardizing US acquisition methods, as well as scoring. US synovitis scores will be acquired at screening, baseline, and pre-infusion at 4, 12, 16, and 24 weeks, to be able to determine whether change in pre-infusion synovitis score at 4 weeks can be used to predict change in disease activity at 12 weeks. This will provide evidence to whether such reading is useful in predicting which patients may require escalation of dose from 4 to 8 mg/kg. At 12 weeks, patients not meeting low disease activity within the 4mg/kg (disease activity score DAS28/ Erythrocyte Sedimentation Rate (ESR)-4item\<3.2) will increase the tocilizumab dose to 8mg/kg (maximum dose 800mg) in a blinded manner to enable evaluation of these US-focused objectives in the context of the current FDA-approved label. The ultrasound scorer will not know information about patient's disease activity (Tender Joint Count (TJC), Swollen Joint Count (SJC), labs etc) or if there was dose escalation at 12 weeks. The clinical assessor of disease activity will be blinded to the ultrasound scores. Additionally, the patient will also be blinded to dose escalation. If patients in the 4mg/kg arm achieve DAS28\<3.2 at 12 weeks, patients will continue with their current dose for the duration of the study. Please see the below Table for details on the blinding plan.
Investigators
Dr. Veena Ranganath
M.D., M.S., Assistant Clinical Professor
University of California, Los Angeles
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tocilizumab
All subjects will receive tocilizumab.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
Time Frame: Baseline, 3 Month
34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level.
Secondary Outcomes
- Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)(Baseline, 6 Month)
- Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints(Baseline, 3 Month)
- Baseline to Month 6 Change in CDAI(Baseline, 6 Month)
- Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints(Baseline, 6 Month)
- Baseline to Month 3 Change in DAS28/ESR(Baseline, 3 month)
- Baseline to Month 6 Change in DAS28/ESR(Baseline, 6 Month)
- Baseline to Month 3 Change in CDAI(Baseline, 3 month)