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Respir Med. 2018 Jan;134:95-102. doi: 10.1016/j.rmed.2017.12.002. Epub 2017 Dec 5.

Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.

Author information

1
National Hospital Organization Tokyo National Hospital, Tokyo, Japan. Electronic address: fueta-tky@umin.ac.jp.
2
Department of Respiratory Medicine, Kyoto University, Kyoto, Japan.
3
National Hospital Organization Tokyo National Hospital, Tokyo, Japan.
4
Department of Respiratory Medicine, Kyoto University, Kyoto, Japan; Department of Respiratory Medicine, Takatsuki Red Cross Hospital, Osaka, Japan.
5
Department of Respiratory Medicine, Kyoto University, Kyoto, Japan; Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University School of Medical Sciences, Aichi, Japan.
6
Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
7
National Hospital Organization Tokyo National Hospital, Tokyo, Japan. Electronic address: kenohta@tokyo-hosp.jp.

Abstract

BACKGROUND:

Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients.

OBJECTIVES:

This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab.

METHODS:

Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed.

RESULTS:

GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49.1 ± 12.5 pg/ml at 32 weeks, P = 0.008; PDGF: 4821 ± 2458 pg/ml at baseline vs. 4219 ± 1951 pg/ml at 32 weeks, P = 0.048).

CONCLUSIONS:

High baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics.

KEYWORDS:

Asthma; CXCL10; IL-12; IgE; Omalizumab

PMID:
29413515
DOI:
10.1016/j.rmed.2017.12.002
[Indexed for MEDLINE]

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