A recent study by Northwestern University Feinberg School of Medicine has demonstrated that genetic profiling of joint tissues can help to determine optimal therapy for RA patients and in turn avoid treatment delays and unnecessary adverse events.

Rheumatoid arthritis (RA) is a debilitating disease with a worldwide prevalence, of 1%. The autoimmune disorder currently has no cure and treatment strategy basically involves a trial and error approach, which ultimately increases the risk of disease progression.

An integrated treatment approach, comprising a mix of pharmacologic agents and nonpharmacologic therapies is followed for optimal care of patients with RA. The standard care for RA includes early therapy with DMARDs (Disease-modifying anti-rheumatic drugs). These include non-biological DMARDs (methotrexate, sulfasalazine, and leflunomide) and biological DMARDs (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab, and certolizumab pegol).

These agents have shown a significant halt in the disease progression and improved rates of clinical remission. Even though DMARDs are considered the mainstay of RA therapy, a lot of patients are unresponsive to them and there has been an increased risk of cardiovascular disease, bone loss, and infection associated with their use.

Precision medicine –paving new horizons for the treatment of rheumatoid arthritis

Precision medicine involves stratifying patients on the basis of genetic, cellular, or molecular markers and utilising those markers for effective treatment and prevention of disease.

As a large amount of heterogeneity has been observed among RA patients, an understanding of the patient’s genetic makeup can certainly pave new horizons for the treatment of RA. Identification of patients with shared biological characteristics and dividing them into homogeneous subgroups can be useful in designing personalised treatment plans and can also assist prompt diagnosis.

The Northwestern University study

Genetic profiling is a powerful weapon to identify biomarkers and it has proved its share in cancer by identifying potentially useful biomarkers which can help in accurately classifying tumours.

RA is a heterogeneous disease, with a number of genetic polymorphisms contributing to disease pathogenesis. This led researchers at the Northwestern University Feinberg School of Medicine, to carry out genetic profiling of joint tissues with the aim of deciphering which specific drug will work for which RA patient.

The study tested the feasibility of using synovial biopsies as a precision medicine approach for RA patients. The study involved 41 patients and was conducted at six study sites around the US. The rheumatologists at all the six sites were well trained in ultrasound-guided synovial tissue biopsy.

Biopsy specimens obtained from the patients were subjected to histologic analysis, fluorescence‐activated cell sorting, and RNA sequencing. The scientists focussed on macrophages, and high-quality RNA‐seq libraries were generated from the isolated macrophage populations. Macrophages are overactive in rheumatoid arthritis and are responsible for producing inflammatory proteins that obliterate the joints.

The researchers correlated the various macrophage transcriptional profiles with the clinical parameters observed in RA patients and segregated patients based on the genes being produced by their macrophages. Six novel transcriptional modules were identified that were found to be associated with disease activity and therapy.

Key findings of the study

Two patient groups were identified who shared aspects of the genetic profiles.

Patients showing joint improvement were identified and this was correlated to the biologics which they were taking.

A gene sequence associated with early disease was also located; this may prove helpful to start early treatment which may ultimately lead to better outcomes, as per the study.

As per the experts, their next goal will be to predict which patients will have the best response to a specific drug based on their genetic profile.

The quest for better therapies- Drive towards a cure

The success of this innovative approach in the clinical setting will be an important step towards personalised treatment for the patients of RA. This, in turn, will lead to early treatment initiation with the most “appropriate drug” and hence will decrease the risk of disease progression and lifelong disabilities.

The quest for better RA therapies is witnessing a lot of excitement and research is ongoing at different levels by targeting different aspects of the devastating disease. Biomarker identification can prove to be a game-changer that could revitalise the current treatment strategy for RA.

Despite all the developments going on at a great pace, much evidence is still needed to be gathered to put together a complete algorithm in the treatment of RA and provide a better quality of life to the patients.