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

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.

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)