Serum GM-CSF Levels May Predict Tocilizumab Treatment Response in RA

Increased baseline levels of granulocyte macrophage-colony stimulating factor (GM-CSF) are a predictor of high disease activity and poor response to tocilizumab (TCZ) therapy among patients with severe rheumatoid arthritis (RA), according to study results published in Arthritis Research & Therapy.

Biological disease-modifying antirheumatic drugs (bDMARDs) are often expensive and may cause adverse effects; roughly 1 in 3 patients with RA do not respond to treatment with bDMARDs. In the current study, researchers aimed to identify the clinical factors that predict treatment response among patients with RA receiving TCZ.

Tocilizumab-naive adult patients with RA who had an insufficient response to methotrexate (MTX) therapy were prospectively recruited from the First Affiliated Hospital of Zhengzhou University in China. The patients received TCZ 8 mg/kg combined with oral MTX every 4 weeks for up to 24 weeks.

Treatment response to TCZ was evaluated using clinical disease activity index (CDAI) scores and categorized as good (achievement of remission or low disease activity), moderate (moderate disease activity), or poor (high disease activity).

A total of 174 patients (85.6% women; mean age, 48.1 years) were included in the final analysis. At week 24, 93 patients presented with a good response to TCZ treatment, 53 had a moderate response, and 28 had a poor response.

Levels of serum proinflammatory cytokines were tested among 142 patients at baseline, while 95 patients had levels retested at weeks 12 and 24. Treatment response was generally good (n=76) or moderate (n=45) among those who received cytokine testing.

According to results of multiple logistic regression analyses, disease duration (odds ratio [OR], 0.996), tender joint count (OR, 0.943), neutrophil ratio (week 4/baseline: OR, 0.2224), and baseline levels of GM-CSF greater than 5 ng/mL (OR, 0.414) were independent adverse predictors of a good response to TCZ.

Predictors of a poor response to treatment included disease activity scores in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) values (OR, 2.951) and elevated baseline levels of GM-CSF greater than 10 ng/mL (OR, 5.419).

Compared against those with low levels, patients with high levels of GM-CSF at 24 weeks had greater DAS28-ESR values and increased serum levels of interleukin (IL)-17A, IL-1β, IL-6, and tumor necrosis factor alpha at baseline.

Patients with high vs low levels of GM-CSF also demonstrated greater rates of moderate/high disease activity (62.8% vs 39.4%; P =.010) and poor response to treatment (27.9% vs 9.1%; P =.004).

“In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline,” the researchers noted. Study limitations include possible selection bias, the limited patient sample size, and limited generalizability to patients with low and moderate levels of RA disease activity.

This article originally appeared on Rheumatology Advisor