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

NCT02321930 | Completed Phase 4 Results

• 1 other identifier: WI193025
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Musculoskeletal Ultrasound; Tofacitinib; biomarker

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline, Week 2, Month 3

• 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.

  Baseline, Week 2, Month 3

• 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.

  Baseline, Week 2, Month 3

• 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).

  Baseline, Week 2, Month 3

Secondary Outcomes (1)

• MBDA

  Baseline, Week 2, Month 3

Study Arms (1)

tofacitinib 5mg po bid

OTHER

Open label with tofacitinib 5mg po bid

Drug: tofacitinib 5mg po bid

Interventions

tofacitinib 5mg po bid DRUG

tofacitinib 5mg po bid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA David Geffen School of Medicine, Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Related Publications (3)

• 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.

  PMID: 34397713 DERIVED

• 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.

  PMID: 33089069 DERIVED

• 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.

  PMID: 32025629 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Veena K. Ranganath
• Organization: UCLA

vranganath@mednet.ucla.edu

310-825-4321

Study Officials

• Veena Ranganath, MD, MS

  UCLA David Geffen School of Medicine, Division of Rheumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: December 22, 2014
• Study Start: February 16, 2016
• Primary Completion: September 29, 2017
• Study Completion: September 29, 2017
• Last Updated: March 19, 2019
• Results First Posted: March 19, 2019

Record last verified: 2019-02

Locations

US (1)