Effekte der Inhibition von Interleukin-12/23p40 versus TNF-α auf die Enthesitis bei Psoriasis Arthritis
Bibliographic record
Abstract
Background and objectives: Enthesitis is often the cause of pain, impaired physical function and structural joint damage in patients with psoriatic arthritis (PsA). Although enthesitis is present in up to 50% of PsA patients, to date, all studies addressing the effects of anti-inflammatory drugs in PsA focused on patients with polyarticular arthritis. Dedicated studies looking at enthesitis are missing. Based on recent knowledge, interleukin-23 (IL-23), a regulatory proinflammatory cytokine, has a central role on the development of enthesitis. Therefore, one can speculate that pharmacological inhibition of IL-23 is particularly effective in treating enthesitis. The primary objective of this study was to evaluate the efficacy of IL-12/23 inhibition (IL-12/23i) and tumor necrosis factor α inhibition (TNFi) in the treatment of enthesitis-driven PsA patients. In addition, the influence of these two therapeutic strategies on other domains of PsA was investigated. Methods: Enthesial CLearance In PSoriatic Arthritis (ECLIPSA) is a prospective randomized- controlled observational study. PsA patients with active enthesitis were randomized 1:1 to receive either ustekinumab (UST; arm 1), an IL-12/23 inhibitor, or a tumor necrosis factor inhibitor (TNFi; arm 2). This is an open label study, so neither physician nor patients were blinded to the treatment drug. Primary endpoint was remission of enthesitis, defined by the Spondyloarthritis Research Consortium of Canada (SPARCC) Index equal to zero at 24 weeks. Through a comprehensive clinical assessment at 12 and 24 weeks, the efficacy of both cytokine-blocking strategies on arthritis, dactylitis and psoriasis was assessed as secondary endpoints. The influence on physical function, fatigue, pain and health-related quality of life was evaluated through previously validated questionnaires. Results and observations: 51 patients (UST = 25; TNFi = 26) were screened, 47 included (UST = 23; TNFi = 24) and 46 completed the study. The SPARCC index was 4 (4) in the UST group and 3.5 (4) in the TNFi group without any significant difference at baseline between the two treatment groups (median (interquartile range)). After 24 weeks, 73.9% of UST patients and 41.7% of TNFi patients met the primary endpoint (SPARCC = 0), indicating remission of enthesitis (p = 0.018). UST was superior to TNFi with regards to enthesitis (SPARCC, p = 0.007) and psoriasis (PASI; p = 0.03) but not arthritis (TJC68/SJC66; p = 0.89/0.96). In terms of physical health-related quality of life (SF36 PCS; p = <0.001), disease activity of the spine (BASDAI; p = 0.005), enthesitis (VAS enthesitis; p = 0.006) and fatigue (FACIT-F; p = <0.001), the group treated with UST showed a significant improvement compared to the TNF group. Conclusions: These results suggest that IL-12/23 inhibition is superior to TNF blockade in the treatment of enthesitis. The presence or absence of enthesitis in PsA could be a guiding parameter for the choice between different cytokine blocking therapies. The superior effects of IL-12/23 inhibition on skin manifestations confirm previous studies on IL-23-dependent pathogenesis of psoriasis. Based on the different efficacy profiles of the biologics, IL-12/23 inhibition through UST could achieve better treatment responses on patients with predominant skin involvement.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".