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Reduced Clinical Improvement in Rheumatoid Arthritis Patients Showing IgG1 Allotype -Infliximab Incompatibility

Lookup NU author(s): Professor John Isaacs

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Abstract

Background IgG1 allotypes (G1m) can induce antibodies in incompatible individuals. Allotypes 1 and 17 are always in the same IgG1 molecule, allotype 2 only appears in IgG1 with allotypes G1m1,17 but it is not present in all the G1m1,17 IgG1s. On the contrary, allotype G1m3 is never in the same IgG1 as the other three allotypes. Infliximab (INF) and Adalimumab (ADM) bear the G1m1,17 allotypes and therefore, they are potentially immunogenic for G1m3 homozygous patients. However, no anti-allotype antibodies were detected in patients treated with ADM in a recent report1.Objectives To assess response to INF and ADM stratified by IgG1 allotype compatibility.Methods Discovery group was made of 206 patients with RA of Spanish ancestry treated with INF (73.3 %) or ADM (26.7 %). Replication group included 404 patients with RA of the UK (359) and Greece (45) treated with INF (49.3 %) or ADM (50.7 %). Disease activity measured by DAS28 was evaluated at baseline and 3, 6 and 12 months in the discovery group and at baseline and 6 months in the replication group. IgG1 allotypes were identified at the DNA level by minisequencing of two discriminating poylmorphisms. Analyses included linear regression of change in DAS28 from baseline and logistic regression of EULAR response criteria (responder/non-responder). Covariates were baseline DAS28, gender and biologic.Results Carriers of the G1m17 allotypes were more often responders than non-carriers at 6 months in the discovery group: 39.1 % responders vs. 27.6 % in the incompatible patients, and 18.5 % non-responders in the compatible patients vs. 28.7 % in the incompatible ones (P = 0.048). Also, compatible patients showed more improvement in DAS28 at 6 months than the incompatible ones (2.4 vs. 1.7, P = 0.02). Stratification showed a significant difference in DAS28 change only in patients treated with INF (P = 0.03). Analysis of the replication group confirmed the results in patients treated with INF; responders (22.4 %) and non-responders (7.8 %) in compatible patients, and responders (9.6 %) and no-responders ( 12.05 %) in incompatible patients with p = 0.03). Also, there was larger improvement in DAS28 in compatible than in incompatible patients (DAS28 = 2.6 vs. 2.2, p = 0.02).Conclusions We have found association between clinical response to INF and compatibility of IgG1 allotypes in RA patients. These results suggest that INF administered to incompatible patients can induce anti-allotype antibodies interfering with treatment. An explanation for the difference between INF and ADM requires further studies.


Publication metadata

Author(s): Montes A, Perez-Pampin E, Navarro-Sarabia F, Moreira V, de la Serna AR, Magallanes B, Vasilopoulos Y, Sarafidou T, Fernandez-Nebro A, Ordonez MDC, Narvaez J, Canete JD, Isaacs J, Morgan A, Barton A, Wilson AG, Gomez-Reino JJ, Gonzalez A, BRAGGGSS

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Annual European Congress of Rheumatology EULAR

Year of Conference: 2013

Pages: A167-A167

ISSN: 1468-2060

Publisher: BMJ Publishing Group

URL: http://dx.doi.org/10.1136/annrheumdis-2013-eular.537

DOI: 10.1136/annrheumdis-2013-eular.537

Library holdings: Search Newcastle University Library for this item

Series Title: Annals of the Rheumatic Diseases

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