HLA-B27 as a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis: data from the Swiss Clinical Quality Management Registry

Fabienne Fröhlich; Raphael Micheroli; Monika Hebeisen; Seraphina Kissling; Kristina Bürki; Pascale Exer; René Bräm; Karin Niedermann; Burkhard Möller; Michael J Nissen; Diego Kyburz; Michael Andor; Oliver Distler; Almut Scherer; Adrian Ciurea

doi:10.1007/s10067-022-06490-8

HLA-B27 as a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis: data from the Swiss Clinical Quality Management Registry

Clin Rheumatol. 2023 May;42(5):1267-1274. doi: 10.1007/s10067-022-06490-8. Epub 2022 Dec 27.

Authors

Affiliations

¹ Department of Rheumatology, Zurich University Hospital, University of Zurich, Gloriastrasse 25, CH-8091, Zurich, Switzerland.
² Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
³ Swiss Clinical Quality Management Foundation, Zurich, Switzerland.
⁴ Gemeinschaftspraxis Rheuma-Basel, Basel, Switzerland.
⁵ Swiss Ankylosing Spondylitis Association, Zurich, Switzerland.
⁶ School of Health Sciences, Institute of Physiotherapy, Zurich University of Applied Sciences, Winterthur, Switzerland.
⁷ Department of Rheumatology and Immunology, Inselspital, Bern, Switzerland.
⁸ Department of Rheumatology, Geneva University Hospital, Geneva, Switzerland.
⁹ Department of Rheumatology, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁰ Rheumatologie im Zürcher Oberland, Uster, Switzerland.
¹¹ Department of Rheumatology, Zurich University Hospital, University of Zurich, Gloriastrasse 25, CH-8091, Zurich, Switzerland. adrian.ciurea@usz.ch.

Abstract

Objective: To explore the impact of the human leucocyte antigen (HLA)-B27 on the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA).

Methods: A total of 1109 patients with available HLA-B27 status (831 B27+ patients and 278 B27- patients) fulfilling the Assessment of Spondyloarthritis international Society classification criteria for axSpA from the prospective Swiss Clinical Quality Management Registry initiating a first TNFi were included. Drug retention was investigated with multiple adjusted Cox proportional hazard models with imputation of missing values. Multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year.

Results: B27+ and B27- patients differed with regard to age, sex, BASDAI, C-reactive protein (CRP), body mass index, enthesitis, uveitis, and classification status. After adjustment for potential confounders for the relationship between HLA-B27 and drug effectiveness (sex and family history of spondyloarthritis), a higher risk of drug discontinuation was found in B27- patients (HR 1.53, 95% CI 1.27-1.83). This difference decreased after additional adjustment for parameters which may act as mediators (HR 1.30, 95% CI 1.30-1.55). Male sex and elevated C-reactive protein (CRP) levels were consistently associated with longer retention. Comparable results were obtained for BASDAI50 responses.

Conclusion: The HLA-B27 genotype is an important predictor of treatment effectiveness. Male sex and CRP seem, however, to better describe variability of response in individual patients. This data may help avoiding potential discrimination of B27- individuals with regard to TNFi initiation. Key Points • HLA-B27 is a predictor of effectiveness of TNF inhibitors in axial spondyloarthritis. • Variability of response in individual patients is better defined by sex and objective markers of disease activity, such as C-reactive protein.

Keywords: Axial spondyloarthritis; HLA-B27; TNF inhibition; Treatment response.

MeSH terms

Axial Spondyloarthritis*
C-Reactive Protein
HLA-B27 Antigen / genetics
Humans
Male
Prospective Studies
Registries
Spondylarthritis* / drug therapy
Spondylarthritis* / genetics
Spondylitis, Ankylosing* / drug therapy
Spondylitis, Ankylosing* / genetics
Switzerland
Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

Tumor Necrosis Factor Inhibitors
HLA-B27 Antigen
C-Reactive Protein