Systemic agent use and mental health outcomes among patients with psoriasis
Bibliographic record
Abstract
Psoriasis is a chronic immune-mediated skin condition affecting 2.5% of the Canadian population.Moderate-to-severe psoriasis is associated with high risks of depression and anxiety.In randomized controlled trials, biologic agents had better efficacy for skin clearance and anxiodepressive symptom reduction than conventional systemic agents (CSA) in patients with In manuscript 3, I described the trajectories of CSA and TNFi/UST use over a 2-year period and compared depression and anxiety-related health care costs between trajectory clusters.My cohort included 781 patients with no history of anxio-depressive disorders.Using sequence and hierarchical cluster analyses, I identified eight treatment trajectory clusters.The overall predicted mean annual cost per-patient was CAN$ 60.Compared to the cluster persistent methotrexate users, the clusters adding a TNFi/UST (cost ratio 3.63, 95% confidence interval, CI 1.47-5.97)and CSA discontinuation then restart on acitretin or multiple switches between CSA (cost ratio 13.30, 95% CI 5.76-22.47)had higher predicted mean costs.Female (versus male) patients had higher predicted mean costs (cost ratio 1.89, 95% CI 1.11-2.69).Results remained unchanged when adjustment disorder-related costs were also considered.In manuscript 4, I assessed the risk of mental health disorders (depression, anxiety and adjustment disorder) in patients initiated on a CSA who subsequently switched/added TNFi/UST (TNFi/UST users) versus (vs) those who did not (TNFi/UST non-users).TNFi/UST users were included in the cohort at the date of TNFi/UST initiation and TNFi/UST non-users were included at a matched date.I separated the TNFi/UST non-user group into those who were currently using a CSA (current CSA users) and those who were not (previous CSA users).My cohort included 183 TNFi/UST users, 625 current CSA users and 525 previous CSA users.Using marginal structural models, TNFi/UST (vs.previous CSA) users were at lower risk for mental health disorders (Hazard Ratio, HR 0.48, 95% CI 0.28-0.94).The result for TNFi/UST vs current CSA users pointed to a nonsignificant lower risk (HR 0.60, 95% CI 0.31-1.20).Findings of this thesis support the importance of considering certain subgroups of patients in the reimbursement process of biologic agents for the treatment of moderate-to-severe psoriasis.Improving access to biologic agents may save patients from the burden of going through a treatment failure experience with CSA and help improve their psoriasis and mental health outcomes faster.v Résumé Le psoriasis est une affection cutanée chronique qui touche 2,5 % de la population canadienne.Le psoriasis modéré à sévère est associé à des risques élevés de dépression et d'anxiété.Dans les essais contrôlés randomisés, les agents biologiques se sont révélés plus efficaces pour la clairance de la peau et la réduction des symptômes anxio-dépressifs lorsque comparés au placebo et aux agents systémiques classiques (CSA) chez les patients atteints de psoriasis modéré à sévère.Cependant, en raison de leurs coûts d'acquisition élevés, les agents biologiques ne sont couverts par le régime public d'assurance-médicaments du Québec que si le traitement par CSA échoue ou est contreindiqué.L'objectif de ma thèse était d'évaluer les schémas d'utilisation des CSA et des agents biologiques (inhibiteurs du facteur de nécrose tumorale et ustekinumab [TNFi/UST]) ainsi que le risque de problèmes de santé mentale et leurs coûts associés chez les patients atteints de psoriasis.Dans mes quatre manuscrits, j'ai utilisé des données provenant des bases de données administratives sur la santé de la province de Québec (1997-2015) et j'ai mené des études de cohorte rétrospectives incluant des patients atteints de psoriasis ayant initié un CSA.Dans les deux premiers manuscrits, j'ai utilisé la même cohorte pour décrire les schémas d'utilisation des CSA et des TNFi/UST et évaluer la présence de disparités entre les sexes dans les facteurs associés au changement de thérapie et à l'arrêt du traitement.Ma cohorte comprenait 1 644 patients.Dans le premier manuscrit, j'ai examiné les CSA en tant que classe.Les taux de changement (ou d'ajout) de TNFi/UST et d'arrêt du CSA étaient respectivement de 44,5 et 364,9 par 1000 personnes-année, sans différence significative entre les sexes.L'âge avancé était associé à un risque réduit de changement de traitement dans les deux sexes.L'obésité et la durée prolongée du psoriasis chez les hommes et les troubles de l'adaptation, somatoformes et dissociatifs chez les femmes étaient associés à un risque accru de changement de traitement, tandis que la présence de polyarthrite rhumatoïde était associée à un risque réduit chez les femmes.Les patients présentant un risque plus faible d'arrêt de CSA étaient les hommes suivis par un rhumatologue et ceux ayant déjà été hospitalisés dans l'année précédente pour toute cause, et les femmes atteintes de polyarthrite rhumatoïde, celles recevant des hypoglycémiants et des hypolipidémiants et celles initiées au méthotrexate (par rapport à tout autre CSA).Dans le deuxième manuscrit, j'ai étudié This thesis would not have been possible without the support of those around me.First and foremost, I would like to express my sincere gratitude to my supervisor Dr Elham Rahme and my co-supervisor Dr Jacques LeLorier for their support, dedication to mentorship and guidance in all aspects of my training.Thank you for sharing your passion and knowledge in pharmacoepidemiology and health economics.I would like to give a special thanks to Dr Rahme, for the opportunity to join her team and for providing an ideal training environment for a doctoral student, even during a global pandemic!I would also like to thank Dr LeLorier for the opportunity to work with him on collaborative projects in pharmacoeconomics.It has been a privilege to work with both of you.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".