Direct and Indirect Effect of Guselkumab on Anxiety, Depression, and Quality of Life in Patients with Moderate-to-Severe Plaque Psoriasis: A Mediation Analysis
Bibliographic record
Abstract
INTRODUCTION: Treating plaque psoriasis (PsO) with guselkumab (GUS) promotes skin clearance and is associated with improvements in health-related quality of life (HRQoL), anxiety, and depression. It is unclear whether improvements in patient-reported outcomes are due to resolution of skin symptoms or the direct result of GUS treatment. METHODS: Two phase 3, placebo- and active-comparator-controlled studies randomized patients with moderate-to-severe PsO to GUS, placebo (crossing over to GUS at week 16), or adalimumab. Post hoc mediation analyses examined direct and indirect effects of GUS, versus adalimumab, on Dermatology Life Quality Index (DLQI) or Hospital Anxiety and Depression Scale (HADS) after adjusting for indirect effects mediated by skin clearance, evaluated via Psoriasis Area and Severity Index (PASI), to determine the direct effect of GUS on dermatology HRQoL, depression, and anxiety. RESULTS: Compared with adalimumab, the natural direct effect (NDE) of GUS on change in DLQI from baseline was - 2.04 (P < 0.001), using PASI improvement as a mediator, indicating 89.2% of the total treatment effect was due to direct effects of GUS; using PASI 90 as a mediator, NDE of GUS was - 1.43 (P < 0.001), with 62.2% of the total treatment effect attributed to direct effects of GUS. Compared with adalimumab, 25.5% of change in HADS anxiety score was mediated through PASI improvement (NDE - 0.74; P = 0.002), indicating 74.5% of the total effect was independent of PASI improvement. Similarly, 24% of treatment effect was mediated through PASI 90 (NDE - 0.76; P = 0.002). Comparable proportions of the total improvement in HADS depression scores were due to direct and indirect effects of GUS mediated through PASI improvement (direct, 50.2%; indirect, 49.8%) or PASI 90 (direct, 59.5%; indirect, 40.5%). CONCLUSIONS: GUS-mediated improvements in anxiety, depression, and overall HRQoL are not solely mediated by resolution of PsO signs, suggesting GUS use has a potential direct effect on anxiety and depression.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".