BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors.

Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.

Infliximab concentrations in two non-switching cohorts of patients with inflammatory bowel disease: originator vs. biosimilar.

Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later. Serum infliximab, antidrug antibody levels and other serum biomarkers were measured at weeks 0, 2, 6, 14 and 22. Remission outcomes were evaluated at weeks 14 and 22. Drug levels were measured prospectively and analysed using MANOVA. Of the 86 patients, 44 (51%) and 42 (49%) were administered the originator and CT-P13, respectively. Originator trough levels were higher than the biosimilar trough levels (35 vs. 21, 20.1 vs. 11, 6.6 vs. 2.9 and 4.3 vs. 1.7 µg/mL at weeks 2, 6, 14 and 22, respectively). A post-hoc analysis demonstrated changes in mean serum drug levels over time (p < 0.001) and according to the drug employed (p = 0.001). At week 22, 13 (81%) patients administered the originator achieved clinical remission compared with 5 (19%) patients with the biosimilar (p = 0.02). None of the patients administered the originator withdrew from the treatment compared with 7 for the biosimilar. During the study, there were significant differences in serum infliximab levels between the originator and the CT-P13 in the patients with IBD. The clinical outcomes were influenced by the type of compound administered.

Optimal concentration range of golimumab in patients with axial spondyloarthritis.

OBJECTIVES: To investigate the association between serum golimumab (GLM) trough levels, clinical disease activity and treatment response during the first year of therapy in patients with axial spondyloarthritis (axSpA), as well as determining an optimal concentration range of GLM in axSpA. METHODS: This was an observational prospective study including 49 patients with axSpA monitored during 52 weeks (W52). Serum GLM trough levels were measured by capture ELISA and antidrug antibodies by bridging ELISA at baseline, W24 and W52. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical improvement by ΔASDAS. The association between serum GLM trough levels and disease activity was assessed using univariable and multivariable regression. In case of drop-out or missing data before W52, the last observation carried forward (LOCF) was performed. ASDAS values and GLM levels at W24 were available for 42 patients and 38 patients at W52. RESULTS: In the univariable analyses, serum GLM trough levels were inversely associated with ASDAS at W24 (n=42, r =-0.445; p<0.01), at W52 (n=38, r=-0.330; p<0.05) and W52LOCF (n=49, r=-0.309; p<0.05). In the multivariable analysis, this significant association remained. Serum trough GLM levels above the 0.7-1.4mg/L range did not contribute to additional clinical improvement. CONCLUSIONS: In patients with axSpA, serum GLM trough levels are associated with disease activity during the first year of treatment. A concentration range of 0.7-1.4mg/L appears to be useful to achieve clinical response to GLM.