Rheumatoid arthritis

Neutrophil levels show which RA patients are destined to fail therapy


The neutrophil-lymphocyte ratio (NLR) may be used to predict the need to escalate early use of biologic therapy in some patients with RA, according to Australian researchers.

The simple and inexpensive test can predict at baseline who would end up having worse outcomes a year down the track, according to their study carried out at the Early Arthritis Clinic at the Royal Adelaide Hospital.

Discussing the results of the study with the limbic, lead author Dr Daniel Bolous, a rheumatologist who now works at the Royal Melbourne Hospital said the NLR outperformed traditional biomarkers for predicting treatment response, including ESR, CRP and DAS28.

“The fact that, even at baseline, the NLR was able to predict who would eventually fail synthetic therapy is a feat that hasn’t been replicated by the other conventional multi-modal measures of disease activity. It goes to show that our best is not good enough.”

The finding is particularly pertinent in Australia he adds, where access to biologic therapy is restricted until after a patient has failed several synthetic disease-modifying antirheumatic drugs (DMARDs).

“Any evidence we have that can help identify the particular subgroup who will end up failing synthetic DMARDs and end up progressing to biologics is very useful – essentially, we can cut to the chase and try to prevent them accruing complications over time while waiting out their due period of service with the synthetic therapies.”

The biomarker, which has been shown to be predictive of poor outcomes in oncology and inflammatory disorders, has not been intensively investigated in rheumatic diseases. Dr Bolous said their findings are the first to examine real world outcomes of RA treatment management in relation to neutrophil levels.

A cohort of 222 patients from the Early Arthritis Clinic at the Royal Adelaide Hospital who were on triple therapy – a standardised protocol of methotrexate, sulfasalazine and hydroxychloroquine – had full blood examinations tracked every three to six weeks

Researchers found the baseline NLR was an independent predictor of treatment response, which was significantly increased in the 20% of patients (n=45) who subsequently went on to fail triple-therapy at their one one-year review.

Despite a ‘modest’ specificity and sensitivity (58% and 67% respectively), the study investigators said the test’s 83% negative predictive value was comparable with other screening tests.

“That’s what we want from a screening test – something that can rule out less aggressive disease so that were not missing those patients with aggressive disease progression. This test is by no means a panacea but it can accurately identify those who are more likely to have low disease activity more than anything else we have, and it highlights those who you need to be a little more watchful and perhaps more aggressive with your therapy.”

Dr Bolous says the true value of the NLR is in its simplicity.

“It doesn’t require further assessments or investigations outside of what is routinely collected during patient review. As a biomarker it can be very easily used as an adjunct to current clinical assessment in cases where perhaps disease control is not quite as good as you think it could be and perhaps escalation of therapy may be worthwhile.”

And that scenario may not be too far away.

“I think the next step would be to see how the NLR in a prospective setting to determine whether the changes in the NLR over time cooperate with the disease activity in a dose response fashion. That would lend credence to the idea of a RCT where biomarker directed decisions could be compared to more conventional care. If that can be demonstrated I think we’re well on our way to having NLR incorporated into decision-making algorithms.”

And pointing out the 80% of patients in the cohort who achieved low disease activity at one year, Dr Bolous said it was ‘worth appreciating’, adding that it reinforced the efficacy of combination therapy after monotherapy failure.

“Everyone in this cohort was treated according to a very strict treat-to-target algorithm and we’ve highlighted how many patients we can get under good disease control, and perhaps how many patients, and how many tax payers, may be spared the progression to biologics if we do follow these very strict treatment algorithms.”

The findings are published in Seminars in Arthritis and Rheumatism.

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