Abstract

Background:Induction of autoantibodies is frequently observed in patients treated with a TNF-α blocker. According to other authors, the incidence of induction of antinuclear antibodies (ANA) and anti-double stranded DNA antibodies (anti-dsDNA) varies between 23-57% and 9-33%, respectively. However, it is unknown whether the induction of these autoantibodies affects the pharmacokinetics and bioavailability of biotherapy and, consequently, reduces the efficacy and safety of the drug.Objectives:To analyze if there is an association between autoantibodies induction and therapeutic efficacy in a monocentric cohort of patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) treated with anti-TNF-α agents.Methods:The authors performed a retrospective analysis of patients with axSpA and PsA treated in our University Hospital with a TNF-α blocker as first biologic agent, and analysed the autoantibodies induction rate after 12 (T12) and 24 (T24) months of therapy. Then, they investigated the influence of autoantibodies in therapeutic efficacy at T12 and T24. Clinical evaluation, laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and disease activity and functional scores (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI, AS Disease Activity Score with CPR - ASDAS-CRP, Bath AS Functional Index - BASFI) were collected from reuma.pt and medical records. For PsA patients, Disease Activity Score-28-CRP (DAS28-CRP), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were also collected. Patients with positive ANA (titer > 1/100) prior to anti-TNF-α therapy were excluded. Continuous variables were analyzed using a t-test and categorical variables using a Chi-square test. P-value <0.05 was considered statistically significant.Results:In the axSpA group, 235 patients were included, 44.5% were females, mean age at diagnosis of 42.3 ± 12.4 years and median disease duration of 11.5 (IQR 6.0-21.0) years. Positive ANA were observed in 16.9% at T12 and 26.3% at T24 and positive anti-dsDNA in 3.4% at T12 and 3.8% at T24, with similar conversion rates between different anti-TNF drugs and no significant gender difference. A significant difference in ASDAS-CPR was found in axSpA patients with and without ANA at T12 (p=0.047). ASDAS-CPR was 1.16 times higher in patients with ANA comparing to patients without them. However, no difference was found in the others disease activity and functional scores at T12. Furthermore, no significant difference, including ASDAS-CPR, was found at T24. Also, there was no significant difference found when comparing patients with and without anti-dsDNA.In the PsA group, 94 patients were included, 46.8% were females, mean age at diagnosis of 46.7 ± 11.7 years and median disease duration of 11.5 (IQR 6.5-16.5) years. Positive ANA were found in 14.9% at T12 and 21.3% at T24 and positive anti-dsDNA in 2.1% at T12 and 3.2% at T24. When comparing the groups with and without ANA and with and without anti-dsDNA at T12 and T24, no significant difference in disease activity and functional scores was found.Conclusion:This study revealed high rates of serology conversion, similar to the rates described before. The authors found that ASDAS-CPR was higher in axSpA patients with ANA after 12 months of therapy. However, this difference was no longer evident after 24 months. No other significant difference was found between patients with and without ANA or with and without anti-dsDNA. The authors consider that the induction of autoantibodies may interfere with the response to anti-TNF-α therapy in a short and initial period of time. Long-term follow-up data are lacking to say whether that influence will disappear consistently over the long run, as they observed after 12 months of therapy. However, they can state that, a priori, seroconversion should not lead to treatment suspension because of concerns about loss of efficacy.Disclosure of Interests:None declared

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