SAT0155 THE PRESENCE OF ANTI-NUCLEAR ANTIBODIES BEFORE ANTI-TNF THERAPY IS A RISK FACTOR FOR THE APPEARANCE OF ANTI-DRUG ANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Shunichi Kumagai, Ayano Mori, Toshiharu Saito, Miho Takahashi, Katsuhiko Yoneda, Yasuhiro Noda, Soushi Takahashi, Miwa Nishida, Saori Hatachi, Goh Tsuji
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> TNF inhibitors (TNFi) revolutionized the treatment of rheumatoid arthritis (RA), but have often developed anti-drug antibodies (ADrA) and also induced other autoimmune pathology<sup>1, 2)</sup>. <h3>Objectives:</h3> To determine whether presence of anti-nuclear antibodies (ANA) predict the development of ADrA and clinical efficacy in RA patients treated with TNFi, infliximab (IFX) or adalimumab (ADA). <h3>Methods:</h3> A total of 92 RA patients, 38 cases treated with IFX and 54 cases with ADA, were prospectively enrolled. Observation period of IFX-treated group was 3 years, and that of ADA-treated group was 1 years. ANA were measured before and serially during the therapy. ANA were measured by indirect fluorescent assay using a Computer-aided microscope system with HEp20-10 cells. The concentrations of anti-IFX antibodies (HACA) and anti-ADA antibodies (AAA) were measured by radioimmunoassay at Sanquin Diagnostic Services, Netherlands. Clinical response to therapy was judged by EULAR response criteria based on Disease Activity Score (DAS) 28-CRP. <h3>Results:</h3> Thirteen (34.2%) of 38 patients in IFX group and 18 (33.3%) of 54 patients in ADA group became positive for HACA and AAA, respectively, during the treatment. All of the ADrA-positive patients were ANA-positive before the therapy. In contrast, none became ADrA-positive after treatment in 15 RA patients negative for ANA before therapy (6 cases in IFX group and 9 cases in ADA group), and the positive rate for ADrA was significantly different between ANA-positive and negative patients (p=0.0018). In addition, the positive rate for HACA was significantly higher in patients positive for ANA titers of ≥640 (p=0.034), but that for AAA was not related to ANA titers. Next, ANA became positive in 4 of 6 ANA-negative patients and ANA titers increased in 21 of 32 ANA-positive patients after IFX treatment. HACA positive rate was significantly higher in patients with ANA titers of ≥640 after IFX treatment (p=0.0045). ANA titers of patients in ADA group were mostly unchanging after treatment, and were not related to the appearance of AAA. Continuance rete of TNFi (IFX and ADA) treatment was significantly lower in ADrA-positive patients than in those negative (p=0.0066 and p=0.0127, respectively). In IFX group, patients with ANA titers of ≥160 before treatment and those with ANA titers of ≥ 320 after treatment positive showed worse EULAR treatment response (p=0.037 and p=0.033, respectively). In ADA group, 7 of 9 ANA-negative patients before treatment showed moderate or good EULAR response, but positive ANA both before and after treatment was not connected with to the clinical response. <h3>Conclusion:</h3> The presence of ANA before IFX or ADA is a risk factor for the appearance of ADrA, while ADrA did not appeared in any patient negative for ANA before treatment. ANA of high titers before and after IFX treatment predicted existence of ADrA and possibly leading to the treatment failure. <h3>References</h3> [1] Kalden JR, Shulze-Koops: Nat Rev Rheumatol, 2017, 13: 707-18. [2] Takase K, et al: Ann Rheum Dis, 2014, 73: 1695-99. <h3>Disclosure of Interests:</h3> Shunichi Kumagai Grant/research support from: Mitsubishi Tanabe Pharm, Eisai Co.Ltd., Ayano Mori: None declared, Toshiharu Saito: None declared, Miho Takahashi: None declared, Katsuhiko Yoneda: None declared, Yasuhiro Noda: None declared, Soushi Takahashi: None declared, Miwa Nishida: None declared, Saori Hatachi: None declared, Goh Tsuji: None declared