Influence of the shared epitope on the effectiveness of biologic antirheumatic agents in European patients with rheumatoid arthritis

BACKGROUND: 'shared epitope' (SE) allele has been proposed as a predictive biomarker for the effectiveness of mainly abatacept and other biologic disease-modifying antirheumatic drugs (bDMARDs). OBJECTIVE: To explore the relative impact of SE positivity on the effectiveness of different bDMARDs in European patients with RA. METHODS: Nested cohort study in the Swiss (Swiss Clinical Quality Management) and Danish (DANBIO) rheumatology registries. Patients with RA who initiated bDMARD treatment and had available DNA samples to define SE were included. Four bDMARD groups were defined: abatacept, tumour necrosis factor inhibitors (TNFi), rituximab, tocilizumab. Patients were matched 1:1 using propensity scores and the effectiveness compared between patients being SE positive versus SE negative. For sensitivity, the number of SE alleles was included. Primary end point was treatment retention (crude by SE status, adjusted Cox regression analyses including relevant covariates). Secondary end points were low disease activity (LDA) and remission (1, 2 years). RESULTS: Of the 5248 treatment courses initially identified, 464 patients in each of the four bDMARD groups were matched (SE negative: 31%, one SE allele: 48%, two alleles: 21%). For all bDMARD groups, crude 1-year treatment retention was unaffected by SE status. Cox regression analyses showed non-significant HRs for SE-positive versus SE-negative patients: abatacept 0.99 (95% CI 0.71 to 1.38), TNFi 1.01 (0.66 to 1.54), rituximab 1.14 (0.71 to 1.84), tocilizumab 1.48 (0.92 to 2.40). LDA and remission rates were unaffected by SE status for all four bDMARDs. Sensitivity analyses showed similar results. CONCLUSION: In the current study, the SE was not associated with bDMARD effectiveness in patients with RA of mainly European ancestry.