Are serum immunoglobulin concentrations a predictive biomarker of response to anti-IL5/IL5Rα therapies?

Background Approval of biologics has recently revolutionized T2 severe asthma management. However, predictive biomarkers remain highly needed to improve patient's selection. Objective This study aims to determine whether serum immunoglobulins (Igs) levels might be predictive biomarkers of response to anti-interleukin-5 (IL5)/IL5Rα therapies. Methods Severe asthma patients eligible for mepolizumab or benralizumab were included herein. Serum immunoglobulin quantification was performed at baseline before mepolizumab or benralizumab initiation. After a 6-month treatment of mepolizumab or benralizumab, patients presented a second serum immunoglobulin quantification. The treatment response was evaluated by the GETE (Global Evaluation of Treatment Effectiveness) score at 6 months. Results A total of 50 patients were included. Median age was 56 [IQR 48.8–65.3] and 50% were females. Compared to baseline, a significant increase in IgG was observed at 6 months (9.2 [7.8–10.2] g/l vs 10.1 [8.8–11.1] g/l, p = 0.04). The area under the ROC curve was 0.58 [95%IC 0.40–0.77] for blood eosinophil count (p = 0.37), 0.75 [95%IC: 0.58–0.92] for serum IgG concentration (p = 0.009) for predicting the treatment response. According to the Youden index, serum IgG concentration ≥ 9.2 g/l predicts the response to anti-IL5 therapies with a sensitivity of 76.9% and a specificity of 75.7%. Conclusion Baseline serum IgG concentrations may be a useful tool to predict the response to anti-IL5/IL5Rα therapies but should be confirmed in larger clinical trials. Interestingly, anti-IL5/IL5Rα therapies are associated with a significant increase in serum IgG concentrations at 6 months.