Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis.

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.

Obesity decreases clinical efficacy and levels of adalimumab in patients with ankylosing spondylitis.

OBJECTIVES: Obesity can be a factor that affects response to anti-TNF drugs. However, studies on patients with ankylosing spondylitis (AS) are rare. We aimed to determine whether obesity affects serum levels of adalimumab (ADL), and immunogenicity and clinical efficacy of the drug in patients with AS. METHODS: A cross-sectional study on 57 patients with axial AS receiving ADL was conducted. They received DMARD per standard of care at their rheumatologist's discretion. Patients' body mass index (BMI) was obtained when ADL treatment began. Clinical response was evaluated using the Spanish versions of the BASDAI index and the ASDAS ESR index. Serum concentrations of free ADL (trough level) and anti-ADL antibodies were measured using Promonitor-ADL and Promonitor Anti-ADL ELISA kits (Progenika Grifols SA, Spain), just prior to the next subcutaneous injection of ADL. RESULTS: Patients with BMI >30 kg/ m2 (obese) as opposed to BMI <25 kg/ m2 (normal), presented lower blood ADL levels [5.0 (5.52) vs. 9.14 (4.3), p=0.032], increased ASDAS scores (2.58 [0.79] vs. 1.9 [0.83], p=0.03), and shorter ADL treatment time: 1.01 [0.84] vs. (1.85 [1.65]; p=0.08]), and increased BASDAI results (5.04 [2.5] vs. 3.5 [1.88]; p=0.06). Obese patients showed a lower probability of clinical response to ADL versus non-obese patients with regard to achieving BASDAI ≤4 (OR: 3.5, 95%CI: 0.84-17.19; p=0.05) or ASDAS ≤2.1 (OR: 4.64, 95%CI: 1.02-24.13; p=0.02). CONCLUSIONS: Of the AS patients receiving treatment with ADL, those that are obese had significantly lower serum ADL levels and decreased clinical response without an increase in immunogenicity.