Secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years
Bibliographic record
Abstract
BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, a key cytokine involved in psoriasis and psoriatic arthritis development, and has shown rapid and long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Monoclonal antibody therapies may be associated with the production of treatment-emergent antidrug antibodies (TE-ADAs) that can affect drug pharmacokinetics, diminish clinical responses via inhibition of target binding or cause hypersensitivity reactions. Secukinumab exhibited minimal immunogenicity up to 52 weeks in patients with moderate-to-severe plaque psoriasis, as evidenced by TE-ADA in <1% patients. OBJECTIVE: To investigate the immunogenicity of secukinumab treatment up to 5 years in two phase 3 extension studies (NCT01640951 and NCT01365455) in patients with moderate-to-severe plaque psoriasis. METHODS: Immunogenicity was evaluated up to Week 268 (5 years). TE-ADAs were defined as positive antidrug antibody (ADA) signals detected in post-treatment samples from patients with negative baseline signals. Confirmed positive samples were further analysed for their neutralizing potential. RESULTS: In total, 1821 patients entered the extension studies. Among patients receiving secukinumab and evaluated for ADAs (n = 1636), 32 developed TE-ADA, which resulted in an incidence of new TE-ADA cases below 1% per year. Neutralizing antibodies were detected in 9/32 (28%) patients with TE-ADA. Half of ADA-positive cases were transient. Among pharmacokinetic samples measured at the times of immunogenicity determination (n = 9992), 544 (5.4%) had secukinumab concentrations higher than the drug tolerance level of 53.8 μg/mL. There was no effect of TE-ADA, including neutralizing antibodies, on efficacy, safety or pharmacokinetics of secukinumab. CONCLUSION: The yearly secukinumab immunogenicity incidence over 5 years of treatment was consistently below 1% in patients with moderate-to-severe plaque psoriasis. Any TE-ADAs, including neutralizing antibodies, were not associated with loss of secukinumab efficacy or with clinical concerns.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".