Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab

Phase 4

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Tocilizumab

Registration Number: NCT01717859

Lead Sponsor: University of California, Los Angeles

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 74

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tocilizumab	Tocilizumab	All subjects will receive tocilizumab.

Primary Outcome Measures

Name	Time	Method
Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)	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 Outcome Measures

Name	Time	Method
Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)	Baseline, 6 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 6 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.
Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints	Baseline, 3 Month	34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. 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 GSUS represents more severe disease level.
Baseline to Month 6 Change in CDAI	Baseline, 6 Month	28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 6 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity.
Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints	Baseline, 6 Month	34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. 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 GSUS represents more severe disease level.
Baseline to Month 3 Change in DAS28/ESR	Baseline, 3 month	28 joints will be evaluated for Tender Joint Count (TJC) and Swollen Joint Count (SJC) as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 3 Month Disease Activity Score (DAS) scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease.
Baseline to Month 6 Change in DAS28/ESR	Baseline, 6 Month	28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 6 Month DAS scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease.
Baseline to Month 3 Change in CDAI	Baseline, 3 month	28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 3 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity.