Neutrophil-lymphocyte ratio (NLR) may be an “inexpensive, objective, and reproducible prognostic marker” in rheumatoid arthritis (RA) to predict the failure of triple therapy in patients, according to research results published in Seminars in Arthritis and Rheumatism.

Researchers aimed to determine if the NLR and platelet-lymphocyte ratio (PLR) might predict which patients require the escalation of disease-modifying antirheumatic therapy due to continued disease activity in RA.

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Recruited patients were a part of the Early Arthritis Clinic at the Royal Adelaide Hospital, and their medical records were retrospectively reviewed. The final analysis included 222 consecutive patients (28% men; mean age, 54.2±15.4 years) with RA who were 18 years or older, met the American College of Rheumatology 1987 revised criteria, and were disease-modifying antirheumatic therapy-naive.

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Patients began triple therapy — a regimen of methotrexate 10 mg orally weekly with concurrent folic acid, sulfasalazine 500 mg daily, and hydroxychloroquine 200 mg twice daily — at initial consultation. The investigators reviewed patients every 3 weeks for the first 12 weeks, every 6 weeks until the patient met the low disease activity target (Disease Activity Score in 28 Joints <3.2), and every 3 months thereafter. Maximum doses of each drug were methotrexate 25 mg/week, sulfasalazine 3 g/d, and hydroxychloroquine 400 mg/d.

Mean polyarthritis disease duration was 22.3±25.0 weeks. By the 1-year review, triple therapy had failed in 20% (n=45) of patients.

Baseline NLR was higher among those patients in whom triple therapy failed at 1 year compared with those patients in whom the therapy did not fail (3.7±2.8 vs 2.9±1.5; P <.02). Neither baseline NLR nor baseline PLR correlated with baseline erythrocyte sedimentation rate, C-reactive protein, or Disease Activity Score in 28 Joints-Erythrocyte Sedimentation Rate.

According to a ROC curve analysis, the cutoff value for the baseline NLR to predict triple therapy failure was 2.70 (sensitivity 67%; specificity 58%). The positive predictive value was 37%, and the negative predictive value was 83%.

Logistic regression analyses also demonstrated that the NLR cutoff value of 2.70 was an independent predictor of triple therapy failure (β, 0.98; standard error, 0.39; odds ratio, 2.65; 95% CI, 1.23-5.72; P =.01).

“In our study, a higher NLR did not appear to correlate with conventional markers of RA disease activity,” researchers concluded. “Despite these considerations, a high NLR at baseline was identified…as an independent predictor of subsequent failure of triple therapy.”

They added, “This predictive property was unique to the NLR and was not seen with conventional markers of disease activity…Further study of this simple biomarker is warranted.”


Boulos D, Proudman SM, Metcalf RG, McWilliams L, Hall C, Wicks IP. The neutrophil-lymphocyte ratio in early rheumatoid arthritis and its ability to predict subsequent failure of triple therapy [published online ahead of print May 31, 2019]. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2019.05.008