263 Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in patients with psoriatic arthritis and ankylosing spondylitis during a 52week treatment period

Background: Secukinumab (SEC), a fully human monoclonal antibody (mAb) that selectively targets interleukin-17A, is highly efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). mAb therapies may be associated with immunogenicity (IG) and production of anti-drug antibodies (ADAs) that may cause adverse events (AEs), and affect drug pharmacokinetics (PK) and clinical response. Objectives: To assess the IG of SEC in PsA and AS patients treated with SEC for up to 52 weeks. Methods: IG in patients with PsA (FUTURE 1-3 studies, n = 1414) and AS (MEASURE 1-4 studies, n = 1163) exposed to SEC was evaluated at baseline (BL) and at weeks 12, 16 (AS only), 24 and 52. Treatment emergent (TE)-ADA were defined as a positive ADA signal in ≥ 1 post-treatment sample in patients negative at BL. TE-ADA positive samples were analysed for drug-neutralising potential, SEC impact on PK, IG-related AEs and TE-ADA impact on efficacy through week 52. Results: Of 1414 treated PsA and 1163 treated AS patients with samples for IG evaluation, 5 (0.35%) and 8 (0.68%), respectively, developed TE-ADAs over 52 weeks (Table 1). All but 1 PsA pt were biologic-naive; 2/5 PsA and 1/8 AS patients received concomitant methotrexate, 2/8 AS patients received concomitant sulfasalazine. Associations between TE-ADAs and SEC dose, frequency or mode of administration were not observed. Other than 1 PsA pt, all TE-ADAs were non-neutralising and none were associated with any IG-related AE. All TE-ADAs were associated with normal PK and none were associated with loss of SEC efficacy over 52 weeks. Conclusion: SEC treatment was associated with a low incidence of IG in PsA and AS patients, as shown by TE-ADA detection in only 0.35% PsA patients and 0.68% AS patients over 52 weeks in a database of > 2500 patients, which is consistent with the low incidence of IG (0.4%) seen with SEC in patients with plaque psoriasis. Overview of pts with TE-ADAa Only positive ADA results at the respective study week are shown; Impact on efficacy is defined as: PsA, failure to achieve >20% reduction, compared to BL, in both tender and swollen joint counts; AS, failure to achieve ASAS20, after previously achieving such improvement for at least two consecutive visits prior to the first detection of ADA; Normal PK: concentrations in ADA-positive pts within observed range for all pts without ADA. ADA, anti-drug antibodies; AE, adverse event; AS, ankylosing spondylitis; ASAS, Assessment of Spondyloarthritis International Society; BL, baseline; IG, immunogenicity; Neut-Ab, neutralising antibodies; N, no; PBO, placebo; PK, pharmacokinetics; PsA, psoriatic arthritis; SEC, secukinumab; TE, treatment emergent; Wk, week; Y, yes. Disclosures: I.B. McInnes: Consultancies; I. M. consulted for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. Member of speakers’ bureau; I. M. participated in a speakers’ bureau with: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. Grants/research support; I. M. received grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. A. Deodhar: Consultancies; A. D. consulted for: Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A. D. received grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. D. Gladman: Grants/research support; D. G. received grant/research support from: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. M. Ren: Other; M. R. is an employee of Novartis. S. Spindeldreher: Shareholder/stock ownership; S. S. is a shareholder at Novartis. Other; S. S. is an employee of Novartis. L. Pricop: Shareholder/stock ownership; L. P. is a shareholder at Novartis. Other; L. P. is an employee of Novartis. B. Porter: Shareholder/stock ownership; B. P. is a shareholder at Novartis. Other; B. P. is an employee of Novartis. J. Safi: Shareholder/stock ownership; J. S. is a shareholder at Novartis. Other; J. S. is an employee of Novartis. A. Shete: Shareholder/stock ownership; A. S. is a shareholder at Novartis. Other; A. S. is an employee of Novartis. G. Bruin: Shareholder/stock ownership; G. B. is a shareholder at Novartis. Other; G. B. is an employee of Novartis.