Candelier, JB

Dass, S

Emery, P

Md Yusof, MY

Rawstron, A

Vital, EM

Annals of the Rheumatic Diseases

White Rose Research Online

This is a repository copy of Validation of B Cell Depletion as A Predictor of Clinical Response and Efficacy of Retreatment of Non-Response in Rheumatoid Arthritis.White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/144376/Version: Accepted VersionProceedings Paper:Md Yusof, MY orcid.org/0000-0003-3131-9121, Candelier, JB, Dass, S et al. (3 more authors) (2016) Validation of B Cell Depletion as A Predictor of Clinical Response and Efficacy of Retreatment of Non-Response in Rheumatoid Arthritis. In: Annals of the Rheumatic Diseases. Annual European Congress of Rheumatology (EULAR 2016), 08-11 Jun 2016, London, UK. BMJ Publishing Group , p. 731. https://doi.org/10.1136/annrheumdis-2016-eular.6122(c) 2016, Published by the BMJ Publishing Group Limited. This is an author produced version of an abstract published in Annals of the Rheumatic Diseases. Uploaded in accordance with the publisher's self-archiving policy.eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. Medical or Research Professionals/CliniciansTopic area: Clinical topics by diseaseTopic: 14. Rheumatoid arthritis - other biologic treatmentEULAR16-6122VALIDATION OF B CELL DEPLETION AS A PREDICTOR OF CLINICAL RESPONSE AND EFFICACY OFRETREATMENT OF NON-RESPONSE IN RHEUMATOID ARTHRITISM. Y. Md Yusof* 1, 2, J. B. Candelier1, S. Dass1, 2, A. Rawstron3, E. M. Vital1, 2, P. Emery1, 21Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2NIHR Leeds MusculoskeletalBiomedical Research Unit, 3Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust,Leeds, United KingdomMy abstract has been or will be presented at a scientific meeting during a 12 months period prior to EULAR 2016: NoIs the first author applying for a travel bursary and/or an award  for undergraduate medical students?: NoBackground: Rituximab has been licensed for the treatment of Rheumatoid Arthritis (RA) for over a decade. Wepreviously showed that the initial depth of B cell depletion was associated with clinical response; 96% complete versus74% incomplete depletion at 6 months (p=0.02)[1] and that retreatment of initial non-responders with incompletedepletion led to 72% response rate in cycle 2 (C2)[2].Objectives: To validate B cell depletion after the first infusion as a predictor of response to rituximab (Project 1) andassess outcome of retreatment of first cycle non-responders (Project 2) as a basis for B cell monitoring during rituximabtreatment.Methods: The published discovery cohorts included 60 patients in Project 1 and 25 patients in Project 2. For thisvalidation study, we analysed the subsequent consecutive 180 patients with RA treated with rituximab at a single centre.Each cycle of rituximab consisted of 2x1000mg infusions, repeated on clinical relapse. B cell subsets (naïve, memory andplasmablast) were measured at baseline, after first infusion of rituximab (2 weeks) and at early B cell repopulation (6months) using a flow cytometry protocol optimized to detect low numbers of B cell subsets and plasmablasts.  Completedepletion was defined as total B cell count <0.0001 x 109/L. First cycle non-responders who had incomplete depletion atC1 were retreated at 6 months. Results: 180 patients (Female=147(81%), median age at rituximab initiation 62(IQR 51-71) years and median diseaseduration 10(IQR 5-18) years were studied. 72(40%) patients were biologic-naïve. In C1, 126 (70%) achieved moderate-good EULAR response. The complete depletion rate for C1 was 54%. Complete depletion was associated with response;p=0.027 (Table 1).30 patients who were C1 non-responders and had incomplete depletion were retreated at 6 months. Ofthese, 20(67%) had complete depletion and 20(67%) responded in C2. Non-responders in C2 had trend to higherplasmablast numbers at retreatment than responders (p=0.14).Table 1:B cell depletion and response in validation cohortProject ACohort Depletion Non Response Response pValidation (n=180) Incomplete 32/82 (39%) 50/82 (61%) 0.036Complete 23/98 (23%) 75/98 (77%)Combined Discovery + Validation (n=240) Incomplete 46/117 (39%) 71/117 (61%) 0.003Complete 26/123(21%) 97/123 (79%)Conclusions: We have validated that the depth of B cell depletion after the first infusion is a predictor of response torituximab in RA. A high degree of response in C2 was also confirmed when C1 non-responders who had incompletedepletion were retreated.  B cell subsets therefore should be monitored in the routine care of RA patients receivingrituximab and repeat infusions considered if early depletion is incomplete and clinical response poor.  References: [1] Dass S et al. A&R 2008 [2] Vital EM et al. A&R 2010Disclosure of Interest: None declared

Validation of B Cell Depletion as A Predictor of Clinical Response and Efficacy of Retreatment of Non-Response in Rheumatoid Arthritis

M.Y. Md Yusof

J.B. Candelier

S. Dass

A. Rawstron

E.M. Vital

P. Emery

Crossref

SAT0175 Validation of B Cell Depletion as A Predictor of Clinical Response and Efficacy of Retreatment of Non-Response in Rheumatoid Arthritis: Table 1.

https://eprints.whiterose.ac.uk/144376/1/EULAR16-ValidationDepletionResponseRA.pdf

Validation of B Cell Depletion as A Predictor of Clinical Response and Efficacy of Retreatment of Non-Response in Rheumatoid Arthritis

Abstract

Similar works

Full text

Available Versions

White Rose Research Online

Crossref