Research & Registry

PROMOTE

PROMOTE
 

Why This Is Important

Genetic studies that test millions of markers require large cohorts and are only possible with your help!  Patients and families have voiced enthusiastic support for this study, and look forward to a tool that could help inform clinical decisions.  

Project Description/Overview

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?

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:

  • Aim 1: we will determine the genetic contribution to clinical drug response using genome-wide SNP arrays
  • Aim 2: we will evaluate the genetic correlations with cellular biomarker measures of drug response including MTX polyglutamate measurements and cellular folate concentrations
  • Aim 3: we will combine our genetic findings with clinical measures to develop a predictive tool that will inform methotrexate use in the clinic.

Enrollment

We will leverage existing patient cohorts and engage in new patient recruitment and sample collection.  We are collaborating with CARRA to identify JIA patients enrolled in the Registry who are initiated on MTX (oral or subcutaneous, at any dose).  The CARRA Registry and Biosample consent forms are used for our study.  We will collect a biosample after 6 months on MTX therapy, or sooner if the patient stops taking MTX or adds a biologic therapy for any reason (and had at least 8 weeks of MTX monotherapy).  Data is entered in the Registry when MTX therapy is initiated, and then 3 months and 6 months post-treatment or at the time the patient stops MTX or add a biologic.  

CARRA-PROMOTE INCLUSION CRITERIA:

All patients with JIA except systemic JIA initiating MTX without an initial biologic therapy to treat their arthritis.
FAQs:

  1. OK to enroll if previously on MTX?
    1. YES! As long as off MTX > 1 year
  2. What if provider plans to start a biologic therapy?
    1. If provider is willing to give the MTX a real chance to work (at least 8 weeks), enroll them!
    2. If the biologic therapy is ordered at onset (and delayed only because of insurance, for example), please do not enroll.
  3. Can I enroll patients already initiated on MTX?
    1. Yes, if we are able to access registry data and still within the sample collection window (8 months from initiation of MTX).  Please contact us to discuss individual cases.
  4. Do I need to do site processing?
    1. NO Centrifugation, aliquoting or refrigeration steps needed.  We provide all supplies and include Mitra microsamplers that are used to wick blood from a small blood tube.

Who is Involved?

PROMOTE

Co-Principal Investigators
Susan Thompson, Ph.D
Mara Becker, M.D., M.S.C.E.

CARRA Leaders
Yuki Kimura, M.D.
Kelly Mieszkalski

Co-Investigators:
Halima Moncrieffe, Ph.D
Laura Ramsey, Ph.D
Daniel Lovell, M.D., M.P.H.
Carl Langefeld, Ph.D
Ashley Cooper, MD

PROMOTE Biobank and Study Coordinators:
Chelsey Smith
Lorie Luyrink
Ashley Leck

DCRI:
Anne Dennos
Kristin Siebenaler
Cheryl Rorick