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 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). We would like to collect a sample ideally at 6 months on therapy, or sooner if the patient needs to stop MTX or add a biologic therapy for toxicity or lack of efficacy.
For CARRA specifically, you can contribute samples to PROMOTE in 2 ways:
- The PROMOTE cohort can include any JIA patient (except SJIA) initiated on MTX. Clinical information will be entered into the registry at baseline (MTX initiation visit), 3 months and 6 months.
- The PROMOTE biosample will ideally be collected at 6 months on therapy (a blood sample for DNA and Mitra collection for biomarker measurements), however, if MTX is stopped or a biologic therapy is added due to MTX toxicity or lack of efficacy between 2 and 6 months, the blood sample will be collected at that point.
- STOP JIA patients on the “Step Up Plan”
- We can leverage the STOP JIA cohort. PROMOTE biomarker samples (Mitra) can be added on to the Precision-Decision (P-D) collection at the 6 month visit and we will use DNA already collected as part of P-D. Or if a P-D baseline sample was not collected, sites can still collect PROMOTE samples at the time of clinical toxicity screening labs at the 6 month (± 2 mo.) visit. In this case, samples will include blood for DNA and biomarkers.
- The PROMOTE study team is coordinating this through the registry to identify STOP-JIA patients and will contact you directly and mail PROMOTE collection kits.
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
Esi Morgan, M.D., M.S.C.E.
Daniel Lovell, M.D., M.P.H.
Yuki Kimura, M.D.
Carl Langefeld, Ph.D
Miranda Wenzlaff M.S., CCRP