José Miguel Senabre Gallego (Marina Baixa Hospital of Villajoyosa, Alicante), José Rosas (Marina Baixa Hospital of Villajoyosa, Alicante), Mariana Marco-Mingot (Marina Baixa Hospital of Villajoyosa, Alicante), José Alberto García-Gómez (General Hospital University of Elche), Gregorio Santos-Soler (Marina Baixa Hospital of Villajoyosa, Alicante), Esteban Salas-Heredia (Marina Baixa Hospital of Villajoyosa, Alicante), Ana Pons-Bas (Marina Baixa Hospital of Villajoyosa, Alicante), Xavier Barber-Vallés (University Miguel Hernández of Elche), José Antonio Bernal‑Vidal (Marina Baixa Hospital of Villajoyosa, Alicante), Catalina Cano-Pérez (Marina Baixa Hospital of Villajoyosa, Alicante), Mario García-Carrasco (Autonomous University of Puebla, Mexico), Emilio Flores-Pardo (University Miguel Hernández of Elche) and AIRE-MB Group (Association of Spanish Rheumatology).

Abstract. Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18–68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5–94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3–95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6–88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.

Keywords. Spondylarthritis; Adalimumab; Antibody formation; Enzyme-linked immunosorbent assay; ROC curve; Treatment outcome