S1319 Seladelpar Treatment Resulted in Correlated Decreases in Serum IL-31 and Pruritus in Patients With Primary Biliary Cholangitis (PBC): Post-Hoc Results from the Phase 3 Randomized, Placebo-Controlled ENHANCE Study
Bibliographic record
Abstract
Introduction: Pruritus is a debilitating symptom impacting the quality of life for many people living with PBC. Interleukin-31 (IL-31) is a cytokine reported to be mechanistically relevant to pruritus and its treatment, including those with cholestasis. Treatment with seladelpar, a selective PPAR-delta agonist, is associated with significant improvement in pruritus in PBC. Here we report the effect of seladelpar on serum IL-31 levels and its association with pruritus in patients with PBC. Methods: IL-31 levels were quantified in serum samples from the ENHANCE study of seladelpar (EudraCT 2018-001171-20) in patients with PBC who received daily oral doses of placebo (n = 55), seladelpar 5 mg (n = 53) or 10 mg (n = 53) for 3 months. Serum IL-31, bile acids and their correlation with patient-reported pruritus numerical rating scale (NRS, 0-10) were assessed. Results: Baseline IL-31 levels positively correlated with pruritus NRS (r = 0.54, P < 0.0001). Patients with NRS ≥ 4 had significantly higher baseline median [IQR] IL-31 compared to patients with pruritus NRS < 4 (7.6 pg/mL [1.2, 14.5] vs 1.2 pg/mL [0.3, 2.8], P < 0.0001). At baseline, IL-31 was also correlated with serum total bile acids (r = 0.54, P < 0.0001) and ALP (r = 0.44, P < 0.0001). Seladelpar treatment strongly decreased mean IL-31 levels from baseline to Month 3: seladelpar 5 mg (3.8 to 1.7 pg/mL, P < 0.001), 10 mg (4.2 to 1.7 pg/mL, P < 0.001) compared to placebo (4.3 to 3.9 pg/mL, not significant). A substantial dose-dependent % decrease in IL-31 was observed with seladelpar treatments: seladelpar 5 mg (-30%, P < 0.001) and 10 mg (-52%, P < 0.0001) compared to placebo (+31%). Patients with a clinically meaningful improvement in pruritus NRS (≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 from baseline compared to those without pruritus improvement. We also observed significant correlations between changes in IL-31 vs pruritus NRS (r = 0.54, P < 0.0001) and ALP (r = 0.40, P < 0.01), but neither with ALT nor AST, in the seladelpar 10 mg group. Changes in IL-31 and total bile acids correlated in the seladelpar 10 mg group (r = 0.63, P < 0.0001). Conclusion: Seladelpar dose-dependently decreased IL-31 in patients with PBC. Reduction in serum IL-31 correlated with pruritus improvement. These results suggest that IL-31 may have a role in pruritus in patients with PBC. It may also be a biomarker related to the anti-pruritic effects of seladelpar (Figure 1).Figure 1.: Effects of seladelpar on IL-31 and pruritus in patients with PBC.
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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) | 0.002 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".