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Precision medicine: the solution to the largest inefficiency in healthcare systems

Rheumatoid arthritis is one of the highest sources of the inefficiency of worldwide health care systems. This could be avoided by more tailored and individualised therapeutic strategies which require better molecular characterization of each patient.

Rheumatoid Arthritis

The situation is caused by a conjunction of multiple facts:

  • The disease has a huge prevalence: about 1% of the worldwide population i.e. 75 million people.
  • This highly debilitating disease generates two sources of huge costs:
    • Indirect costs arise when the disease is very aggressive or not satisfactorily treated, which causes incapability to work and long-term cares such as Kinesio-/physiotherapy.
    • Direct costs are the costs of the drugs used to treat rheumatoid arthritis. The available drugs, called Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are either synthetic or biologic.
Treatment guidelines

In a nutshell, international guidelines, such as the ones from the European League Against Rheumatism (EULAR) recommend first using synthetic DMARDs, then if these fail to trigger a response, to switch to biological DMARD. Synthetic DMARDs are affordable but only effective in about 60% of cases. That still makes 0.4% of the worldwide population not adequately treated (that is still 30 million people). For these, biological DMARDs are initiated. There are about 10 such drugs.

Financial burden

Given the burden of the disease, all DMARDs are reimbursed/financed for the patients in most developed countries even if biological DMARDs are very expensive. The cost is about 10-15kEur/year per patient, potentially life-long as RA is a chronic disease. This represents a huge burden for the healthcare systems. In Belgium, for example, the two most prescribed biological DMARDs count for more than €200 million each year. That is Belgium’s highest expense for drugs. The situation is similar in many countries.

Guidelines explicitly include a random drug choice

Worse than that, each biological DMARD is also only effective in about 60% (on average) of the patients, and each will be effective on different patients. And the main pain point is that there is no standard way for the rheumatologists to know a priori which drug will be effective for which patient. The current strategy, even in the official guidelines, is to proceed by trial-and-error. Knowing it takes 3 to 6 months just to witness the non-response to a treatment, the waste, both in terms of direct costs and of the quality of life (the disease progresses meanwhile) and indirect costs are tremendous.

Precision medicine: towards a molecular-based drug prescription

Fortunately, these biological DMARDs rely on very distinct mechanisms of actions. Some of them inhibit the TNF pathway. Others target B-Cell activation, T-Cell activation, or specific interleukins (IL6, IL17, …). And other alternatives are coming on the market, namely several JAK inhibitors. But are rheumatologists able to characterise each patient with respect to these mechanisms before choosing between available DMARDs? No. This was not possible until very recently.

Recent works allow profiling the transcriptome of the synovial tissue from inflamed joints of the patients, right at the site where rheumatoid arthritis is the most active. Synovial biopsy is becoming a commodity, with both EULAR and ACR (Amercian College of Rheumatology) organising massive training at continental levels. Ultrasound-guided synovial biopsy has been shown to be very well tolerated by patients. This metabolic profiling combined with advanced data mining and online applicative software allows comparison of the level of activity of several metabolic pathways. The motivation is the following: why prescribe an anti-TNF as a first guess, if the patient synovial tissue shows there is only a very low activity of the TNF pathway, while at the same time, B-Cell activation seems very high? In such a case, why not favour the prescription of an anti-CD20 DMARD?

This kind of tool offers already the metabolic characterization of each patient, unblinding the rheumatologists, and potentially reducing the hundreds of million euros wasted each year by healthcare systems. The metabolic processes are however not fully known, and clinical studies are ongoing to go even one step further than metabolic characterization: really provide treatment response prediction tools for each individual patient.

ThibaultHelleputte260

Thibault Helleputte is CEO of DNAlytics. He will be presenting at the 4th Global Precision Medicine & Biomarkers Leaders Summit.

Download the agenda to see what other topics are being covered 

One Response to “Precision medicine: the solution to the largest inefficiency in healthcare systems”

  1. Look at Genefron, an Israeli company. They developed a blood test to determine responders and nonresponders to Anti-tnf for RA. This will eventually increase efficiency and save costs once it hits the markets.

    Reply

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