Brodalumab: The first anti-IL-17 receptor agent for psoriasis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef). The U.S. Food and Drug Administration has also recently approved brodalumab (Siliq) for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Regulatory applications are under review in the E.U. and Canada. The phase III clinical trials in moderate to severe plaque psoriasis met their primary endpoints after 12 weeks' treatment, with PASI 75 (75% improvement in the Psoriasis Area and Severity Index) response rates ranging between 83% and 86% (210 mg) and PASI 100 response rates ranging between 37% and 44%, significantly higher than those achieved with ustekinumab in the head-to-head trials AMAGINE-1 and AMAGINE-2. The most frequently reported adverse events in brodalumab clinical trials consisted of nasopharyngitis, headache, upper respiratory tract infection and arthralgia. In the head-to-head trials, rates of neutropenia were higher with both active drugs than with placebo, and mild or moderate Candida infections were more frequent with brodalumab than with ustekinumab or placebo. Clinical development was terminated by Amgen after adverse events of suicidal ideation and behavior were observed ls involving several indications, but data are inconclusive regarding potential drug causality, and brodalumab has recently been approved in the U.S. with a black box warning and a risk-management program regarding suicidal issues. Blocking IL-17RA provides a highly efficacious therapeutic alternative for moderate to severe psoriasis with a satisfactory safety profile.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 it