Precision Medicine in Rheumatology May Improve Diagnosis, Disease Classification

The increased use of personalized, or precision, medicine will greatly affect the field of rheumatology, according to the lead author of a recent editorial in the New England Journal of Medicine. The article, “Precision medicine—personalized, problematic and promising,” examined how rapid advances in genetics and new disease classifications will alter the medical practice of the future.¹

“In fields like rheumatology, there is a proliferation of new biomarkers and an enhanced ability to assess immune responses,” says lead author J. Larry Jameson, MD, PhD, executive vice president of the University of Pennsylvania and dean of the Perelman School of Medicine in Philadelphia. “A practical implication of these advances is that it is no longer possible for generalists to keep pace with the rapidly expanding knowledge base relevant for diagnosing and managing most serious diseases. As I note in the article, the generalist of the future will need greater support from information technology, and we will need to develop more effective ways of engaging the expertise of subspecialists.”

The No. 1 opportunity for rheumatologists “is likely to be selective modulation of immune responses, either by manipulating regulatory T cells or by eliminating cells that recognize specific antigens,” he says.

Recently, Dr. Jameson discussed this subject with The Rheumatologist:

Question: Many rheumatologists define their practice as “personalized.” How might personalized, or precision, medicine affect the practices of rheumatologists and their patients in years to come?

Dr. Jameson: I am not a rheumatologist, so I can only make some general predictions about the future of the specialty. I foresee three major changes:

1. Access to diagnostic tools that allow better classification of autoimmune disorders—These tools will include genetic tests that reveal predisposition biomarkers that display disease activation and better measurements of immune responses;
2. Access to a new armamentarium of treatments that alter the course of disease, ideally in its earliest stages—These tools will include an expansion of antibodies, but will also include strategies to modulate responses of T cells, B cells, plasma cells, cytokines and the innate immune system. Recent examples using genetically modified, autologous T cells foreshadow these approaches. A goal will be to disrupt the course of autoimmune diseases before there is significant organ damage; and
3. Managing the care of patients whose primary medical problem is rheumatologic—This reflects both the complexity of providing targeted therapies, but also ensuring that side effects are detected and other medications do not exacerbate an underlying rheumatologic disorder.

Question: The article states, “Clinical implications will be greatest when results of genetic testing are actionable.” How does this apply to rheumatology practice?

Dr. Jameson: Genetic testing can be useful in at least four ways:

1. To make a definitive diagnosis when disease penetrance is high;
2. To predict prognosis;
3. To allow targeted treatment; and
4. To allow genetic counseling.

In the case of rheumatologic disorders, most genetic testing at the present time would involve genetic predisposition (e.g., HLAB27). It seems likely that genetic associations will improve over time. The results will be actionable either because the diagnosis is more definitive and/or there is a specific, targeted treatment for the immune abnormality.

Question: You also write, “Financial incentives for new diagnostic tests are not as strong as those to create new drugs.” Do you foresee a palatable, near-term solution, or is this where the government and policymakers need to intervene?

Dr. Jameson: A likely scenario is the need to couple diagnostic tests and targeted treatments. That is, the targeted treatment will not be indicated without evidence of a specific biomarker. In this case, the pharmaceutical companies will be incentivized to develop these tests. Payers are also likely to require documentation of treatment efficacy to justify continuing to pay for expensive therapies.

Question: What is your biggest concern about technology as a driver of precision medicine?

Dr. Jameson: The challenge of [technology is] keeping up with the knowledge base and developing a set of incentives … that allows patients to benefit from the advances. The benefits of precision medicine will not be realized unless there is reimbursement for testing, targeted treatments and consultations by specialists.

Richard Quinn is a freelance writer in New Jersey.

References

1. Larry JL, Longo DL. Precision medicine—personalized, problematic and promising. N Engl J Med. 2015 Jun 4;372(23):2229–34. doi: 10.1056/NEJMsb1503104