PROMOTE is an NIH-funded multi-center study (R01HD089928) that aims to identify pharmacogenomic predictors of methotrexate (MTX) response. We hypothesize that methotrexate response in JIA is dependent on genetic variation influencing drug metabolism and drug bioavailability. If we can identify responders to MTX at the onset of therapy, we may avoid unnecessary biologic therapies, and conversely, if a patient is predicted to be a non-responder to MTX, we can escalate to a biologic therapy sooner, and not waste time on MTX.
The study is organized into 3 specific aims: In aim 1 we will determine the genetic contribution to clinical drug response using genome-wide SNP arrays; in aim 2 we will evaluate the genetic correlations with cellular biomarker measures of drug response and in aim 3 we will combine our genetic findings with clinical measures to develop a predictive tool that will inform methotrexate use in the clinic.
We have the support and collaboration of several groups to help us test our hypothesis and specific aims. We will leverage existing patient cohorts and engage in new patient recruitment and sample collection. We are collaborating with CARRA (through STOP JIA and Precision Decisions to STOP JIA) and PR-COIN to utilize existing research registry networks to identify JIA patients treated with MTX. We are interested in JIA patients who are initiated on MTX (oral or subcutaneous, at any dose) who remain on MTX for at least 6 months (regardless of if a biologic was added after initiation).
For CARRA specifically, you can contribute samples to PROMOTE in 2 ways:
STOP JIA patients on the “Step Up Plan”
- PRECISION DECISION (P-D): Collect PROMOTE biomarker samples at the 6 month visit using Mitra microsamplers. These will be available in kits provided for P-D collection. (and use DNA already collected as part of P-D)
- If a P-D baseline sample was not collected, sites can enroll STOP JIA patients in PROMOTE at the 6 month (± 2 mo.) visit and collect PROMOTE samples at the time of clinical toxicity screening labs. The samples will be include blood for DNA and Mitra microsamplers for biomarkers.
- Once STOP JIA is complete, the PROMOTE collection will continue. The PROMOTE cohort can include any JIA patient (except SJIA) initiated on MTX. Clinical information will be entered into the registry at baseline, 3 months and 6 months.
- The PROMOTE biosamples needed at baseline are blood to measure folate status and extract DNA and at 6 months Mitra collection for biomarker measurement.
Collectively, we can take a personalized medicine approach to help answer the real question: what drug is the best choice for our JIA patients at the onset of therapy?
Susan Thompson, Ph.D
Mara Becker, M.D., M.S.C.E.
Halima Moncrieffe, Ph.D
Laura Ramsey, Ph.D
Leon van Haandel, PhD
Esi Morgan, M.D., M.S.C.E.
Daniel Lovell, M.D., M.P.H.
Yuki Kimura, M.D.
Carl Langefeld, Ph.D
Kelly Mieszkalski, M.A.