Research @ WMR 

Our Tradition of Clinical Research 

WMR Research Portfolio

Over the past two decades, researchers at the West Michigan Rheumatology have been at the forefront of innovative, cutting-edge clinical research in rheumatology. Our physicians and team have conducted a large number of investigations for new agents in rheumatic diseases.  

Click on the link below to learn about the specific therapeutic area that interests you.


News About Research @ West Michigan Rheumatology 

We want to do research that is relevent to your care, as well as respected by our peers on national stage.  Browse the blog below to learn about about some of the ways which we share our experience with peers nationally. 


Results of WMR Raynauds and Digital Ulcer Study Reported

JAMA The Journal of the American Medical Association 315(18):1975-1988 · May 2016 

Abstract

Importance: Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker. Objective: To evaluate the efficacy of macitentan in reducing the number of new digital ulcers in patients with systemic sclerosis. Conclusions and relevance: Among patients with systemic sclerosis and active ischemic digital ulcers, treatment with macitentan did not reduce new digital ulcers over 16 weeks. These results do not support the use of macitentan for the treatment of digital ulcers in this patient population. Trial registration: clinicaltrials.gov Identifiers: NCT01474109, NCT01474122.

SLE Study Co-lead by Dr. Martin Identifies New Treatment Direction

Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus

ArticleinThe Journal of Immunology 197(7) · August 2016

Abstract

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.

WMR SLE patients major contributors in discovery of new mechanisms of lupus related inflammation.

OP0186 Immune Complex Bound U1 and Y1 RNA Correlates with Interferon-Stimulated Gene Expression and Disease Activity: An Observational Study of Sysytemic Lupus Erythematosus Patients

ArticleinAnnals of the Rheumatic Diseases 75(Suppl 2):127.2-127 · June 2016with2 Reads

DOI: 10.1136/annrheumdis-2016-eular.2747

Abstract

Background Immune complexes (ICs) containing RNA are thought to play a central role in driving interferon (IFN) production and systemic inflammation in systemic lupus erythematosus (SLE) via activation of intracellular Toll-Like Receptors (TLRs). However, quantitation of IC-bound RNAs in SLE patient plasma has not previously been performed. Objectives To quantify IC-associated U1 and Y1 RNA and relate the findings to the interferon (IFN) signature and SLE clinical activity. Methods Medications and SLEDAI measurements were completed on 228 SLE patients > 50 from West Michigan.

Results  Within the U1 RNA-positive groups, the top 10 up-regulated genes were increased 10–48 fold compared to healthy volunteers (associated p values exceeding 10–15) and corresponded to known IFN-inducible transcripts. IC-bound U1 and Y1 RNA levels showed significant correlations with each other and also with disease activity (SLEDAI) (p<0.0003). 

Conclusions The enhanced expression of IFN-inducible transcripts in blood from patients possessing IC-bound U1 and/or Y1 RNA lends further support to the hypothesis that these RNA molecules are involved in triggering TLR7 and stimulating interferon production in SLE patients. Therapeutic strategies that seek to reduce the quantities of RNA associated with ICs may be an attractive approach to blocking downstream IFN production and immune system activation. 

Results of early phase anti- IL-17 reported from WMR


Dr. Martin, Head and Eggebeen and colleagues reported the results of an early phase clinical trial conducted at West Michigan Rheumatology as a part of their broader thread of investigations of innovative biologic therapy for rheumatoid arthritis.  

Click the link to access the article


International Research Collaboration

BMC Medical Informatics & Decision Making 2013

Dr. Martin and colleagues in the International Patient Decision Aid Standards Collaboration published updated 

Quality Dimensions: Theoretical Rationales, Current Evidence, and Emerging Issues.    

These specifically address the state of the art "Providing information about options in patient decision aids".

These provide guidance to developers of patient decision aids regarding length, content, and information architecture design.

Rheumatologists at WMR are recognized as leaders in the design and implementation of educational interventions that support shared decision making about complex biologic anti-rheumatic drugs.

Click the link to access the article

Providing information about options in patient decision aids


Click the link to access the full document 

International Patient Decision Aid Standards (IPDAS) Collaboration’s Quality Dimensions: Theoretical Rationales, Current Evidence, and Emerging Issues.


Dr. Eggebeen & Rituximab in Myositis (RIM) Study Group

Dermatomyositis

Inflammatory cells around and invading into muscle cells causing damage to skeletal muscle and weakness in patients.

After more than 5 years of meticulous planning and arduous execution Dr. Eggebeen and national colleagues have completed the multicenter "Rituximab in Myositis Study" the results have been published in the Nov 2 edition of Arthritis and Rheumatism. This is the first of many publications which will arise from this landmark clincal trial which evaluates the effects of the B-cell depleting monoclonal antibody rituximab on children and adults with polymyositis and dermatomyositis that was resistent to standard therapies.  Although no significant differences were detected between the treatment groups, 83% of refractory adult and juvenile myositis patients met the definition of improvement by the end of the trial. 

Dr. Head Moderates National Research

The American College of Rheumatology National Scientific Meeting is the premier venue for reporting rheumatology research.  

Dr. Andrew Head was nominated and served on the abstract selection committee for the Rheumatoid Arthritis: Biologics and Small Molecules section for 2010, 2011, 2012.  

Here he moderates an oral session in Washington DC.

Promoting the Use of Patient Decision Aids

A new Study Group was launched at the American College of Rheumatology National Scientific Meeting to promote research and adoption of patient decision aids in rheumatology.   


Topics explored included:

  • Knowledge Translation Using Patient Decision Aids - a Canadian View

Peter Tugwell, MD, MSc

Canadian Research Chair in Health Equity University of Ottawa


  • How Decision Aids Differ from Other Forms of Patient Information 

Rich Martin, MD, MA

Professor of Medicine, Rheumatology     Michigan State University


  • Use and value of conjoint analysis to ascertain patient treatment preferences

Liana Fraenkel, MD, MSc

Associate Professor of Medicine (Rheumatology)     Yale University


What motivates RA patients to increase care?

Research presented by investigators at WMR at the American College of Rheumatology National Scientific Meeting in Washington, DC.

Background:

The prescription of Disease Modifying Anti-rheumatic Drugs (DMARD) for patients with rheumatoid arthritis (RA) is considered a standard of effective care.

  • However only 63% of US Medicare managed care and 43% Canadian provincial RA patients take a DMARD.
  • The explanation for underutilization is not fully known.

Methods: 

A single center, randomized controlled factorial design cross-sectional mail survey of RA patients in a large regional-community rheumatology practice.

Patients were presented a hypothetical decision scenario where they were asked to consider switching DMARDs. They evaluated how risky the proposed medication was and how likely they would be to take it.

Results: 

Of 1538 RA patients, 1009 or 71% completed the study.  Regression modeling evaluated predictors of risk perception and willingness to take the proposed medication.

Conclusions:

  • Risk Perception was predicted by negative RA disease and treatment experience.
  • Willingness to take a proposed DMARD was predicted by current satisfaction with disease control.
  • Race and sex did not predict risk perception or DMARD willingness.
  • Depression did not predict risk perception or DMARD willingness.
  • Health literacy, independent of low education or demographics, was a common predictor of both risk perception and or DMARD willingness.

Main take home point:  

Cognitive bias, related to low health literacy, is a recognizable patient trait that may contribute to underutilization of DMARDs, and can potentially be accommodated with patient decision support

WMR Faculty Publishes Invited Manuscript

RDC NA


In November Rheumatic Disease Clinics of North America will publish a special issue focusing on “Drug Safety: Managing Innovation in Rheumatology.”  This includes invited manuscripts from national experts including WMR faculty,  Dr. Richard Martin.  WMR has a productive research thread evaluating risk communication related to anti-rheumatic drugs which has been recently received increasing national attention.  This is another example of relevant research which translates to improved patient care. 


Article synopsis:  When proposing a new therapy, rheumatologists must inform patients of a range of therapeutic options and support them towards making an informed decision.   These decisions are often made over time and involve multiple stakeholders.   This article introduces definitions of equipoise and a good decision, contrast persuasion from informed patient choice, and discuss the effects of patient characteristics including cognition on decision-making.  In addition it describes, and offers examples, of techniques and visual formats to present risk estimates to reduce cognitive bias and maximize patient comprehension. 

Read more at the National Library of Medicine website 

by clicking here. 

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