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Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
tofacitinib 5mg po bid
Sponsored by
University of California, Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Musculoskeletal Ultrasound, Tofacitinib, biomarker

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient must meet 1987 ACR criteria
  2. Age > 18 years of age
  3. Baseline DAS28/ESR>=3.2
  4. Stable concomitant DMARDs
  5. Stable prednisone <10mg or equivalent
  6. Power Doppler score of >=10
  7. Female subjects of childbearing potential must test negative for pregnancy
  8. Male and female subjects of childbearing potential must agree to use contraception throughout the study
  9. Negative QuantiFERON Gold test at screening

Exclusion Criteria:

  1. No active TB
  2. Prednisone >10 mg
  3. Pregnancy or breast feeding
  4. Prior treatment with tofacitinib
  5. Concomitant biologic therapy (TNF inhibitors, IL-6 inhibitors, etc.)
  6. Active infection with HIV, hepatitis B or C, or herpes zoster

  7. Subjects with any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:

    1. Evidence of hematopoietic disorder or hemoglobin <9 g/dL
    2. Absolute lymphocyte count <0.75 x 109/L (<750/mm3)
    3. Absolute neutrophil count <1.2 x 109/L (<1200/mm3)
    4. Platelet count <100 x 109/L (<100,000/mm3)
    5. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (x ULN)
    6. Estimated GFR <40 ml/min
  8. Subjects who have received live or live attenuated vaccines within 6 weeks prior to the first dose of study drug (or the zoster vaccine)
  9. Subjects who require concomitant treatment with medications that are potent inhibitors of cytochrome P450 3A4 (CYP3A4), both moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, and potent CYP inducers (See Appendix)

Sites / Locations

  • UCLA David Geffen School of Medicine, Division of Rheumatology

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

tofacitinib 5mg po bid

Arm Description

Open label with tofacitinib 5mg po bid

Outcomes

Primary Outcome Measures

PDUS
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS. The Power Doppler Synovitis Score (PDUS) ranges from 0 to 90. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for PDUS represents more severe disease level.
GSUS
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS. The grey scale synovial hypertrophy score (GSUS) ranges from 0 to 90. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for GSUS represents more severe disease level.
CDAI
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity.
DAS28/ESR
TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. Patient Global Assessment of disease activity was scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. ESR lab value were included in the total calculation. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation.The scale ranges from 0 to 9.4, where higher values represent a higher disease activity.The complete formula to calculate DAS28/ESR is 0.56*sqrt(TJC) + (0.28*sqrt(SJC)) + (0.7*ln(ESR)) + (0.014*Patient Global*10).

Secondary Outcome Measures

MBDA
The multi-biomarker disease activity (MBDA) blood test assesses RA disease activity. An algorithm of 12 markers is used to characterize RA disease activity on a scale of 1-100, where a score of 100 represents the highest level of disease activity present.

Full Information

First Posted
September 23, 2014
Last Updated
February 27, 2019
Sponsor
University of California, Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT02321930
Brief Title
Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients
Official Title
Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
February 16, 2016 (undefined)
Primary Completion Date
September 29, 2017 (Actual)
Study Completion Date
September 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This proposal will evaluate if musculoskeletal ultrasound (MSUS) measures or multi-biomarker disease activity (MBDA) improve in patients treated with tofacitinib over 3 months, and whether early MSUS measures/MBDA can predict response to therapy.
Detailed Description
This is a pilot open-label trial of 25 RA patients treated with tofacitinib over 3 months. The patients meeting inclusion criteria will be started on tofacitinib 5mg po bid. Patients will be recruited from the UCLA Rheumatology Clinics. Inclusion criteria will include the following: meeting ACR 1987 RA criteria, DAS28≥3.2, age≥18, and PDUS>10 (see below for more details). Patients who are deemed unsafe to enroll will be excluded. Ultrasound measures (PDUS/GSUS) and MBDA scores will be obtained at screen, baseline, 2 weeks, and 3 months. In addition, we will also obtain HAQ-DI, CDAI, and DAS28 at the same time points. In addition, we will have a 6 week visit for capturing adverse events, concomitant drugs, drug dispensation, and evaluation of adherence. Currently, there are several US measures to evaluate therapeutic response in RA patients that have been used in the literature. Some US studies evaluate all joints involved in RA, which is time consuming. At present, there is no consensus as to the ideal ultrasound scoring system. However, we will utilize a 34-joint US scoring system to evaluate response to therapy in this proposal (see Table 1). Our research team has expertise in MSUS (given several workshops/lectures nationally) and we have proficiency in designing/conducting MSUS clinical trials. We currently have 4 ultrasonography-rheumatologists at UCLA who are ACR certified in MSUS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Musculoskeletal Ultrasound, Tofacitinib, biomarker

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tofacitinib 5mg po bid
Arm Type
Other
Arm Description
Open label with tofacitinib 5mg po bid
Intervention Type
Drug
Intervention Name(s)
tofacitinib 5mg po bid
Primary Outcome Measure Information:
Title
PDUS
Description
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS. The Power Doppler Synovitis Score (PDUS) ranges from 0 to 90. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for PDUS represents more severe disease level.
Time Frame
Baseline, Week 2, Month 3
Title
GSUS
Description
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS. The grey scale synovial hypertrophy score (GSUS) ranges from 0 to 90. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for GSUS represents more severe disease level.
Time Frame
Baseline, Week 2, Month 3
Title
CDAI
Description
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity.
Time Frame
Baseline, Week 2, Month 3
Title
DAS28/ESR
Description
TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. Patient Global Assessment of disease activity was scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. ESR lab value were included in the total calculation. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation.The scale ranges from 0 to 9.4, where higher values represent a higher disease activity.The complete formula to calculate DAS28/ESR is 0.56*sqrt(TJC) + (0.28*sqrt(SJC)) + (0.7*ln(ESR)) + (0.014*Patient Global*10).
Time Frame
Baseline, Week 2, Month 3
Secondary Outcome Measure Information:
Title
MBDA
Description
The multi-biomarker disease activity (MBDA) blood test assesses RA disease activity. An algorithm of 12 markers is used to characterize RA disease activity on a scale of 1-100, where a score of 100 represents the highest level of disease activity present.
Time Frame
Baseline, Week 2, Month 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must meet 1987 ACR criteria Age > 18 years of age Baseline DAS28/ESR>=3.2 Stable concomitant DMARDs Stable prednisone <10mg or equivalent Power Doppler score of >=10 Female subjects of childbearing potential must test negative for pregnancy Male and female subjects of childbearing potential must agree to use contraception throughout the study Negative QuantiFERON Gold test at screening Exclusion Criteria: No active TB Prednisone >10 mg Pregnancy or breast feeding Prior treatment with tofacitinib Concomitant biologic therapy (TNF inhibitors, IL-6 inhibitors, etc.) Active infection with HIV, hepatitis B or C, or herpes zoster Subjects with any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities: Evidence of hematopoietic disorder or hemoglobin <9 g/dL Absolute lymphocyte count <0.75 x 109/L (<750/mm3) Absolute neutrophil count <1.2 x 109/L (<1200/mm3) Platelet count <100 x 109/L (<100,000/mm3) Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (x ULN) Estimated GFR <40 ml/min Subjects who have received live or live attenuated vaccines within 6 weeks prior to the first dose of study drug (or the zoster vaccine) Subjects who require concomitant treatment with medications that are potent inhibitors of cytochrome P450 3A4 (CYP3A4), both moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, and potent CYP inducers (See Appendix)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veena Ranganath, MD, MS
Organizational Affiliation
UCLA David Geffen School of Medicine, Division of Rheumatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA David Geffen School of Medicine, Division of Rheumatology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34397713
Citation
Kim SK, Jung UH, Kim JW, Choe JY. The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis: Preliminarily data from single center-based observational study for 24 weeks. Medicine (Baltimore). 2021 Jul 30;100(30):e26739. doi: 10.1097/MD.0000000000026739.
Results Reference
derived
PubMed Identifier
33089069
Citation
Razmjou AA, Brook J, Elashoff D, Kaeley G, Choi S, Kermani T, Ranganath VK. Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis. BMC Rheumatol. 2020 Oct 19;4:55. doi: 10.1186/s41927-020-00153-4. eCollection 2020.
Results Reference
derived
PubMed Identifier
32025629
Citation
Choate EA, Kaeley GS, Brook J, Altman RD, FitzGerald JD, Floegel-Shetty AR, Elashoff DA, Ranganath VK. Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients. BMC Rheumatol. 2020 Feb 3;4:8. doi: 10.1186/s41927-019-0107-2. eCollection 2020.
Results Reference
derived

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Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients

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