Clinical trial NCT02321930: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Musculoskeletal Ultrasound
Tofacitinib
biomarker
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2014-12-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: PDUS
timeFrame: Baseline, Week 2, Month 3
measure: GSUS
timeFrame: Baseline, Week 2, Month 3
measure: CDAI
timeFrame: Baseline, Week 2, Month 3
measure: DAS28/ESR
timeFrame: Baseline, Week 2, Month 3
Secondary outcomes:
measure: MBDA
timeFrame: Baseline, Week 2, Month 3
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine, Division of Rheumatology
state: California
Study officials:
affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology
name: Veena Ranganath, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.