POS1195 CAN PRE-TREATMENT INFLAMMATORY BIOMARKER LEVELS GUIDE TO DETERMINE APPROPRIATE TIME OF TOCILIZUMAB THERAPY IN COVID-19

Abstract

BackgroundDue to the pleiotropic cytokine interleukin-6 (IL-6) plays a pivotal role in the pathogenesis of COVID- 19, tocilizumab, an inhibitor of the IL-6 receptors, was considered as an attractive therapeutic option. When the inflammation cascade is excessive and therapy is delayed, the efforts for suppression of inflammation does not necessarily reduce mortality in all cases. Besides, early using anti-cytokine therapy may lead to both increased cost and risks including iatrogenic immunosuppression (1). Defining of patients who will benefit from tocilizumab and determining optimal timing of tocilizumab will prevent drug-related side effects and increased costs due to unnecessary drug use.ObjectivesTo investigate the reliability of pre-treatment levels of prognostic nutritional index (PNI), C-reactive protein/albumin ratio (CAR), systemic immune-inflammatory index (SII), IL-6, lactate dehydrogenase (LDH) as a treatment response biomarker in hospitalized COVID-19 patients who administered tocilizumab.MethodsOne hundred thirty three COVID-19 patients received tocilizumab were included. The end-points of treatment effectiveness were evaluated with the rate of death and emerging need for mechanical ventilation at 28 days of hospitalization. To determine independent mortality risk factors, multivariate logistic regression analyzes were performed for statistically different variables among groups that were statistically different in univariate analysis. The capacity of IL-6, CAR, PNI, SII and LDH values in predicting of tocilizumab response in COVID-19 patients were analyzed using receiver operating characteristic (ROC) curve analysis.Results34 (25.56%) patients died after tocilizumab therapy. Patients who improved after tocilizumab were significantly younger and had significantly lower IL-6, LDH, SII, CAR and higher PNI than patients who died. In univariate analyses, mortality was significantly associated with age, IL-6, LDH, PNI, SII, CAR and CRP. In multivariate analysis, age (OR:1.070, 95%CI:1.019-1.124, p:0.007) and LDH (OR:1.006, 95CI%:1.003- 1.010, p<0.001) were found to be independent predictors of mortality after tocilizumab therapy. To identify of tocilizumab response in COVID-19 patients, IL6 had the highest area under curve (AUC) value (AUC:0.782, 95%CI:0694-0.870), followed by LDH (AUC:0.761, 95%CI:0.661-0.861), PNI (AUC:0.696, 95%CI:0.584-807), SII (AUC:0.671, 95%CI:0.551–0.790), CAR (AUC:0.682, 95%CI:0.578– 0.786) and CRP (AUC:0.643, 95%CI:0.535–0.751). Predictive performance of inflammatory biomarkers in the prediction of mortality after tocilizumab therapy was presented in Table 1.Table 1.Predictive performance of inflammatory biomarkers in the prediction of mortality after tocilizumab therapySensitivitySpecificityPLRNLRPPVNPVAccuracyDORIL-6 (pg/mL) >143.1264.71%84.85%4.270.4259.46%87.50%79.70%10.27LDH (U/L) >46073.53%71.72%2.600.3747.17%88.75 %72.18%7.04PNI<31.3555.88%79.80%2.770.5548.72%84.04%73.68%5.00SII>3895.9247.06%90.91%5.180.5864.00%83.33%79.70%8.89CAR>61.1561.76%67.68%1.910.5639.62%83.75%66.17%3.38CAR: C-reactive protein/albumin ratio; DOR: diagnostic odds ratio; IL-6: interleukin-6; LDH: lactate dehydrogenase; NLR: negative likelihood ratio; NPV: negative predictive value; PLR: positive likelihood ratio; PNI: prognostic nutritional index; PPV: positive predictive value; SII: systemic immune-inflammatory index.ConclusionAlthough the patients with significantly lower IL-6, LDH, SII, CAR and higher PNI levels improved after tocilizumab therapy, only serum LDH levels and age were found to be as independent predictors of mortality. To specify the optimal time interval and the patients who will benefit from tocilizumab, these biomarkers may be used.