Increased expression of <scp>IL</scp>‐17A and limited involvement of <scp>IL</scp>‐23 in patients with palmo‐plantar (<scp>PP</scp>) pustular psoriasis or <scp>PP</scp> pustulosis; results from a randomised controlled trial
Bibliographic record
Abstract
BACKGROUND: Palmo-plantar pustular psoriasis (PPPP) and palmo-plantar pustulosis (PPP) are chronic skin diseases with significant impact on quality of life. OBJECTIVES: The purpose of this study was to study the efficacy of ustekinumab in PPPP and PPP and gain more knowledge on the pathophysiology and the role of the interleukin-23 (IL-23) signalling pathway in these diseases. METHODS: Thirty-three patients with either PPPP (20) or PPP (13) and seven volunteers with normal palmo-plantar skin were recruited. Patients with PPP or PPPP were randomised (1 : 1) to receive either an anti IL-12/IL-23 antibody (ustekinumab 45 mg) or placebo at day 0 and week 4 with subsequent placebo cross-over to ustekinumab at week 16. The primary endpoint was the proportion of patients randomized to ustekinumab achieving a 50% improvement in the Palmo-Plantar Pustular Area and Severity Index (PPPASI-50) as compared to placebo. Skin biopsies of the palms and soles of normal subjects and patients with PPP or PPPP were performed and analysed by RT-PCR and immunohistochemistry. RESULTS: There was no statistically significant difference in the proportion of patients randomised to ustekinumab as compared to those randomised to placebo achieving PPPASI-50 at week 16 for patients with PPPP (10%, 20%; P = 1.000) or PPP (20%, 37.5%; P = 1.000) respectively. Compared to normal subjects an 89-fold increase in IL-17A expression was found in palms/soles of patients with PPPP (P = 0.006) and a 190-fold increase for patients with PPP (P = 0.051). There were no statistically significant changes in cytokine expression at week 16 in the palms and soles of patients with PPP or PPPP. CONCLUSION: Taken together these results suggest that ustekinumab at a dose of 45 mg has limited efficacy in PPPP and PPP. IL-17A may have a more important role than IL-23 in patients with PPPP and PPP. Conclusions are limited by the small sample size of this study.
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How this classification was reachedexpand
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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".