Corrigendum to: Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden.

[This corrects the article DOI: 10.1093/rap/rkaa070.][This corrects the article DOI: 10.1093/rap/rkaa070.].

Health and work disability outcomes in parents of patients with schizophrenia associated with antipsychotic exposure by the offspring.

This study aimed to identify if antipsychotic exposure in offspring is associated with psychiatric and non-psychiatric healthcare service use and work disability of their parents. This Swedish population-based cohort study was based on data comprising 10,883 individuals with schizophrenia, who had at least one identifiable parent in the nationwide registers, and their parents (N = 18,215). The register-based follow-up during 2006-2013 considered the level of antipsychotic exposure and persistence of use of the offspring, further categorized into first (FG) and second generation (SG) antipsychotics, and orals versus long-acting injections (LAIs). The main outcome measure was parental psychiatric healthcare service use, secondary outcomes were non-psychiatric healthcare use and long-term sickness absence. SG-LAI use was associated with a decreased risk (relative risks [RR] 0.81-0.85) of parental psychiatric healthcare use compared with not using SG-LAI, whereas oral antipsychotics were associated with an increased risk (RRs 1.10-1.29). Both FG- and SG-LAI use by the offspring were associated with a lower risk of long-term sickness absence (range of odds ratios 0.34-0.47) for the parents, compared with non-use of these drugs. The choice of antipsychotic treatment for the offspring may have an impact on work disability and healthcare service use of their parents.

Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden.

OBJECTIVES: TNF inhibitors (TNFis) and IL inhibitors are effective treatments for PsA. Treatment non-persistence (drug survival, discontinuation) is a measure of effectiveness, tolerability and patient satisfaction or preferences in real-world clinical practice. Persistence on these treatments is not well understood in European PsA populations. The aim of this study was to compare time to non-persistence for either ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-17 inhibitor) to a reference group of adalimumab (TNFi) treatment exposures in PsA patients and identify risk factors for non-persistence. METHODS: A total of 4649 exposures of adalimumab, ustekinumab, and secukinumab in 3918 PsA patients were identified in Swedish longitudinal population-based registry data. Kaplan-Meier curves were constructed to measure treatment-specific real-world risk of non-persistence and adjusted Cox proportional hazards models were estimated to identify risk factors associated with non-persistence. RESULTS: Ustekinumab was associated with a lower risk of non-persistence relative to adalimumab in biologic-naïve [hazard ratio (HR) 0.48 (95% CI 0.33, 0.69)] and biologic-experienced patients [HR 0.65 (95% CI 0.56, 0.76)], while secukinumab was associated with a lower risk in biologic-naïve patients [HR 0.65 (95% CI 0.49, 0.86)] but a higher risk of non-persistence in biologic-experienced patients [HR 1.20 (95% CI 1.03, 1.40)]. Biologic non-persistence was also associated with female sex, axial involvement, recent disease onset, biologic treatment experience and no psoriasis. CONCLUSION: Ustekinumab exhibits a favourable treatment persistency profile relative to adalimumab overall and across lines of treatment. The performance of secukinumab is dependent on biologic experience. Persistence and risk factors for non-persistence should be accounted for when determining an optimal treatment plan for patients.

Burden for Parents of Patients With Schizophrenia-A Nationwide Comparative Study of Parents of Offspring With Rheumatoid Arthritis, Multiple Sclerosis, Epilepsy, and Healthy Controls.

BACKGROUND: The study aimed to (1) compare the risk of health care use, adverse health status, and work productivity loss of parents of patients with schizophrenia to parents of patients with multiple sclerosis (MS), rheumatoid arthritis (RA), epilepsy, and healthy controls; and (2) evaluate such outcome measures while considering disease severity of schizophrenia. METHODS: Based on linkage of Swedish registers, at least one parent was included (n = 18215) of patients with schizophrenia (information 2006-2013, n = 10883). Similarly, parental information was linked to patients with MS, RA, epilepsy, and matched healthy controls, comprising 11292, 15516, 34715, and 18408 parents, respectively. Disease severity of schizophrenia was analyzed. Different regression models yielding odds ratios (OR), hazard ratios (HR), or relative risks (RR) with 95% confidence intervals (CI) were run. RESULTS: Psychiatric health care use, mainly due to anxiety and affective disorders, showed a strongly increasing trend for parents of patients with schizophrenia throughout the observation period. During the follow-up, these parents had an up to 2.7 times higher risk of specialized psychiatric health care and receipt of social welfare benefits than other parents. Parents of the moderately severely ill patients with schizophrenia had higher risk estimates for psychiatric health care (RR: 1.12; 95% CI: 1.07-1.17) compared with parents of least severely ill patients. CONCLUSIONS: Parents of patients with schizophrenia have a considerably higher risk of psychiatric health care and social welfare benefit receipt than other parents. Psychiatric health care use worsens over time and with increasing disease severity of the offspring.

Cost-effectiveness of ustekinumab in moderate to severe Crohn's disease in Sweden.

BACKGROUND: Human monoclonal antibody ustekinumab is a novel Crohn's disease (CD) treatment blocking pro-inflammatory cytokines interleukin-12 and 23. The study's objective was to assess cost-effectiveness of ustekinumab in moderate to severely active CD in Sweden. METHODS: A cost-effectiveness model with an induction phase decision-tree structure and a maintenance phase Markov cohort structure was constructed. CD was represented by five health-states: remission, mild, moderate-severe, surgery and death. Ustekinumab was compared to adalimumab in patients who had failed conventional care, some of which had tried TNF-alpha-inhibitor(s) without experiencing treatment failure or side effects ("conventional care failure population") and to vedolizumab in patients previously failing TNF-alpha-inhibitor treatment. Discontinuation probabilities, utilities and ustekinumab induction efficacy were sourced from phase-III trials. Maintenance and comparator efficacy came from network-meta and treatment-sequence analyses. Resource use and unit costs were derived from literature and validated by clinical experts. The analysis had a societal perspective, a life-time time-horizon, and 2-year treatment duration. The results robustness was tested in univariate and probabilistic sensitivity analyses. Cost-effectiveness was estimated using quality-adjusted life-years (QALYs). RESULTS: Ustekinumab dominated adalimumab in conventional care failure population (costs: - €6984, QALYs: + 0.232). In TNF-alpha-inhibitor failure population ustekinumab accrued 0.133 more QALYs than vedolizumab, yielding a €30,282 incremental cost-effectiveness ratio. Results were sensitive to decreasing the time horizon and increased treatment duration. At Swedish reference willingness-to-pay of €63,000 (SEK 600,000), ustekinumab had 94% probability of being cost-effective versus adalimumab, and 72% versus vedolizumab. CONCLUSIONS: Results indicate ustekinumab dominates adalimumab in conventional care failure population, and is cost-effective versus vedolizumab in TNF-alpha-inhibitor failure population.

Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia.

INTRODUCTION: It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. METHODS: We linked prospectively gathered nationwide register-based data during 2006-2013 to study all-cause mortality among all patients aged 16-64years with schizophrenia in Sweden (N=29,823 in total; N=4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. RESULTS: During the mean follow-up of 5.7years, 2515 patients (8.4%) died. During the maximum follow-up (7.5years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01-1.86) for first generation (FG) LAIs, 1.52 (1.13-2.05) for SG orals, 1.83 (1.33-2.50) for FG orals, and 3.39 (2.53-4.56) for nonuse of antipsychotics. Concerning specific agents, the lowest mortality was observed for once-monthly paliperidone LAI (0.11, 0.03-0.43), oral aripiprazole (0.22, 0.15-0.34), and risperidone LAI (0.31, 0.23-0.43). In pairwise comparison, LAIs were associated with 33% lower mortality than equivalent orals (0.67, 0.56-0.80). The results with incident cohort were consistent with the primary analyses. CONCLUSIONS: Among patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality.

Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia.

Importance: It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies. Objective: To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia. Design, Setting, and Participants: Prospectively gathered nationwide databases were linked to study the risk of rehospitalization and treatment failure from July 1, 2006, to December 31, 2013, among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29 823 patients in the total prevalent cohort; 4603 in the incident cohort of newly diagnosed patients). Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias. Traditional Cox proportional hazards multivariate regression was used for secondary analyses. Main Outcomes and Measures: Risk of rehospitalization and treatment failure (defined as psychiatric rehospitalization, suicide attempt, discontinuation or switch to other medication, or death). Results: There were 29 823 patients (12 822 women and 17 001 men; mean [SD] age, 44.9 [12.0] years). During follow-up, 13 042 of 29 823 patients (43.7%) were rehospitalized, and 20 225 of 28 189 patients (71.7%) experienced treatment failure. The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR, 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR, 0.58; 95% CI, 0.44-0.77) compared with no use of antipsychotic medication. Oral flupentixol (HR, 0.92; 95% CI, 0.74-1.14), quetiapine (HR, 0.91; 95% CI, 0.83-1.00), and oral perphenazine (HR, 0.86; 95% CI, 0.77-0.97) were associated with the highest risk of rehospitalization. Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78; 95% CI, 0.72-0.84 in the total cohort; HR, 0.68; 95% CI, 0.53-0.86 in the incident cohort). Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine. The results of several sensitivity analyses were consistent with those of the primary analyses. Conclusions and Relevance: Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations.