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
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".