Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus

Md Yusof, M.Y., Shaw, D., El-Sherbiny, Y.M. ORCID: 0000-0003-4791-3475, Dunn, E., Rawstron, A.C., Emery, P. and Vital, E.M., 2017. Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus. Annals of the Rheumatic Diseases, 76 (11), pp. 1829-1836. ISSN 0003-4967

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Abstract

Objective: To assess factors associated with primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) and evaluate management of secondary non-depletion non-response (2NDNR).

Methods: 125 patients with SLE treated with rituximab over 12 years were studied prospectively. A major clinical response was defined as improvement of all active British Isles Lupus Assessment Group (BILAG)-2004 domains to grade C/better and no A/B flare. Partial responders were defined by one persistent BILAG B. B-cell subsets were measured using highly sensitive flow cytometry. Patients with 2NDNR, defined by infusion reaction and defective depletion, were treated with ocrelizumab or ofatumumab.

Results: 117 patients had evaluable data. In cycle 1 (C1), 96/117 (82%) achieved BILAG response (major=50%, partial=32%). In multivariable analysis, younger age (OR 0.97, 95% CI 0.94 to 1.00) and B-cell depletion at 6 weeks (OR 3.22, 95% CI 1.24 to 8.33) increased the odds of major response. Complete depletion was predicted by normal complement and lower pre-rituximab plasmablasts and was not associated with increased serious infection post-rituximab. Seventy-seven (with data on 72) C1 responders were retreated on clinical relapse. Of these, 61/72 (85%) responded in cycle 2 (C2). Of the 11 C2 non-responders, nine met 2NDNR criteria (incidence=12%) and tested positive for anti-rituximab antibodies. Lack of concomitant immunosuppressant and higher pre-rituximab plasmablasts predicted 2NDNR. Five were switched to ocrelizumab/ofatumumab, and all depleted and responded.

Conclusion: Treatment with anti-CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. 2NDNR is associated with anti-rituximab antibodies, and switching to humanised agents restores depletion and response. In SLE, alternative anti-CD20 antibodies may be more consistently effective.

Item Type: Journal article
Publication Title: Annals of the Rheumatic Diseases
Creators: Md Yusof, M.Y., Shaw, D., El-Sherbiny, Y.M., Dunn, E., Rawstron, A.C., Emery, P. and Vital, E.M.
Publisher: BMJ Group
Date: 2017
Volume: 76
Number: 11
ISSN: 0003-4967
Identifiers:
NumberType
10.1136/annrheumdis-2017-211191DOI
Rights: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 20 May 2019 13:08
Last Modified: 20 May 2019 13:08
URI: http://irep.ntu.ac.uk/id/eprint/36610

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