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

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.

Early axial spondyloarthritis according to the ASAS consensus definition: characterisation of patients and effectiveness of a first TNF inhibitor in a large observational registry

“… 18 We have previously demonstrated that CRP and male sex seem to better describe the variability of treatment responses than HLA-B27 in individual patients. 24 An elevated CRP or a higher ASDAS was consistently associated with significantly better TNFi effectiveness in the analyses presented here. Indeed, CRP was shown to be the best predictor of good response in numerous prospective trials in both radiographical and non-radiographical disease and seems better than sacroiliac inflammation detected by MRI, as demonstrated in subgroup analyses.…”

HLA-B27 status and inflammatory MRI lesions of the sacroiliac joints: a post hoc analysis in patients without axial spondyloarthritis

“…The HLA-B27 status is considered an important predictor in the diagnosis and treatment management of axSpA, 18 while its role in LBP on non-inflammatory origin has received limited attention thus far. Recent studies showed that in the general population, HLA-B27 status influences the extent of BMO at SIJ, especially in men.…”

How to translate genetic findings into clinical applications in spondyloarthritis?

“…The most frequent reported associations were with polymorphisms in TNFRSF1A/1B (TNF receptor superfamily member 1A/1B) and TNF but results were often conflicting. HLA-B27, not included in this systematic literature review, has also been identified as a predictor of good response to TNF blockers ( 31 ).…”