Comparison of Paliperidone Palmitate and Risperidone Long-Acting Injection in Schizophrenic Patients: Results From a Multicenter Retrospective Cohort Study in France.

PURPOSE/BACKGROUND: The study objective was to compare the impact of being treated by paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) on the length of stay on initial hospitalization, rehospitalization risk, and treatment duration in schizophrenic patients. METHODS: We conducted an observational retrospective cohort study in 43 centers in France, including schizophrenic patients who initiated a treatment by PP or RLAI during initial hospitalization. The follow-up periods started in September 2012 for the RLAI group (median follow-up duration, 233 days) and in June 2013 for the PP group (259 days). Statistical analyses were based on Cox regression models, with propensity score weighting to account for differences in patients' characteristics. FINDINGS/RESULTS: The analysis included 347 patients: 197 in the PP treatment group and 150 in the RLAI group. Compared with patients on RLAI, patients on PP were significantly more likely to have nonpsychiatric comorbidities, to have been on previous antipsychotic therapy, or to have been hospitalized for psychiatric care in the previous year. With regard to length of stay on initial hospitalization, there was no statistically significant difference between both groups (hazard ratio, 1.13 [0.97; 1.31]). Being on PP was associated with similar times to first rehospitalization compared with RLAI (hazard ratio, 0.92 [0.65; 1.30]). IMPLICATIONS/CONCLUSIONS: We observed nonsignificant differences in initial hospitalization duration and time to rehospitalization between PP and RLAI, potentially due to lack of statistical power. A trend was observed in favor of PP with regard to time to treatment discontinuation, although this result was compromised by patients who switched between RLAI and PP.

Factors Influencing Patient and Caregiver Preferences for Antipsychotic Treatment of Schizophrenia in China: A Discrete Choice Experiment.

Purpose: This study aimed to quantify the preferences of Chinese patients with schizophrenia and their caregivers for antipsychotic treatment. Patients and Methods: Patients with schizophrenia (aged 18-35) and their caregivers were recruited via six outpatient mental health clinics in Shanghai, People's Republic of China. In a discrete choice experiment (DCE), participants chose between two hypothetical treatment scenarios that varied regarding the type of treatment, rate of hospitalization, severity of positive symptoms, treatment cost and rates of improvement in daily and social functioning. Data for each group were analyzed using the modelling approach that yielded the lower deviance information criterion. The relative importance score (RIS) for each treatment attribute was also determined. Results: A total of 162 patients and 167 caregivers participated. Frequency of hospital admission was the most important treatment attribute for patients (average scaled RIS=27%), followed by mode and frequency of treatment administration (24%). Improvement in ability to carry out daily activities (8%) and improvement in social functioning (8%) were least important. Patients in full-time employment placed more importance on the frequency of hospital admission than unemployed patients (p<0.01). Frequency of hospital admission was also the most important attribute for caregivers (RIS=33%), followed by improvement in positive symptoms (20%), while improvement in daily activities (7%) was the least important. Conclusion: Patients with Schizophrenia in China prefer treatments that help reduce the number of times they are admitted to hospital, as do their caregivers. These results may bring insight for physicians and health authorities in China regarding the treatment characteristics that patients value the most.

Efficacy of ustekinumab vs. advanced therapies for the treatment of moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

Objective: To compare the relative efficacy of ustekinumab (UST) vs. other therapies for 1-year response and remission rates in patients with moderate-severe UC.Methods: Randomized controlled trials reporting induction and maintenance efficacy of anti-TNFs (infliximab [IFX], adalimumab [ADA], golimumab [GOL]), vedolizumab (VDZ), tofacitinib (TOF) or UST were identified through a systematic literature review (SLR). Analyses were conducted for clinical response, clinical remission and endoscopic-mucosal healing for populations with and without failure of prior biologics (non-biologic failure [NBF]; biologic failure [BF]). Maintenance data from trials with re-randomized response designs were re-calculated to correspond to treat-through arms. Bayesian network meta-analyses (NMA) were conducted to obtain posterior distribution probabilities for UST to perform better than comparators.Results: Six trials included NBF patients and four included BF patients. In NBF patients, UST as a 1-year regimen showed higher probabilities of clinical response, remission and endoscopic-mucosal healing vs. all treatments: Bayesian probabilities of UST being better than active therapies ranged from 91% (VDZ) to 100% (ADA) for response; 82% (VDZ) to 99% (ADA) for remission and 82% (IFX) to 100% (ADA and GOL) for endoscopic-mucosal healing. In BF patients, UST was the most effective treatment (Q8W dose); however, effect sizes were smaller than in the NBF population.Conclusions: Results indicate a higher likelihood of response, remission and endoscopic-mucosal healing at 1 year with UST vs. comparators in the NBF population. In BF patients, a higher likelihood of response to UST vs. the most comparators was also observed, although results were more uncertain.

Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: The interaction of IL-5 with its receptor on eosinophils increases the activation and maintenance of eosinophils; blocking this interaction reduces asthma symptoms in patients with the eosinophilic phenotype. Reslizumab, which binds to IL-5, and benralizumab, which targets the IL-5 receptor α subunit, have not been compared in head-to-head trials. OBJECTIVE: To indirectly compare reslizumab with benralizumab in similar patient populations using a network meta-analysis. METHODS: A systematic literature review was conducted and a network meta-analysis was performed on eligible studies using the Markov Chain Monte-Carlo simulation method and a Bayesian statistical framework. RESULTS: Eleven studies were identified, 4 of which evaluated clinically relevant doses and had outcomes at similar time points. To control for population differences, subgroups were selected for the base-case efficacy analysis: a benralizumab subgroup with blood eosinophil levels of greater than or equal to 300 cells/µL (n = 1537) and a reslizumab subgroup in Global Initiative for Asthma step 4/5 with 2 or more previous exacerbations and greater than or equal to 400 eosinophils/µL (n = 318). Safety was analyzed in the full population (N = 3462). Reslizumab significantly improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) scores compared with benralizumab once every 4 weeks and there were reasonably high posterior probabilities that reslizumab is superior to benralizumab once every 4 weeks and once every 8 weeks for ACQ score, AQLQ score, FEV1, and clinical asthma exacerbations. CONCLUSIONS: This indirect comparison suggests that reslizumab may be more efficacious than benralizumab in patients with eosinophilic asthma in Global Initiative for Asthma step 4/5 with elevated blood eosinophil levels (benralizumab, ≥300/µL; reslizumab, ≥400/µL) and 2 or more exacerbations in the previous year.

Bucher's indirect comparison of daylight photodynamic therapy with methyl aminolevulinate cream versus diclofenac plus hyaluronic acid gel for the treatment of multiple actinic keratosis.

Actinic keratosis (AK) is a pre-cancerous condition characterised by patches of thick, scaly skin developing on sun-exposed areas of the body. When multiple AKs develop on severely photodamaged skin, commonly used treatments include photodynamic therapy and diclofenac plus hyaluronic acid gel (DHA). Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is an alternative to conventional photodynamic therapy (MAL c-PDT). Trials have indicated that MAL DL-PDT is as effective as MAL c-PDT but reduces treatment-related pain and dermatological side effects. To indirectly compare between MAL DL-PDT and DHA in patients with AK. A total of three randomised trials were collected using a systematic literature review. An adjusted indirect comparison was conducted on complete lesion response rate at 12 weeks. The data indicated that mild lesions, moderate lesions, and mild and moderate lesions treated with MAL DL-PDT were more than four times more likely to undergo a complete response than lesions treated with DHA at 12 weeks, with ORs ranging from 4.23 to 4.81. Results were all statistically significant. This is the first indirect comparison demonstrating the effectiveness of MAL-PDT over DHA for the treatment of AK, and further research is needed to assess the long-term efficacy of these interventions (i.e. six months and beyond), as well as safety and patient-reported outcomes.

Patient and physician preferences for the treatment of chronic hepatitis C virus infections: does the perspective matter?

OBJECTIVES: The objectives of this study were to identify and quantify the factors driving patient and physician preferences for treatments of genotype 1 hepatitis C virus infection in the UK. METHODS: A web survey was conducted, including 100 patients (50 treatment-naive and 50 treatment-experienced patients) and 50 physicians (gastroenterologists/ hepatologists and infectious disease specialists). A discrete-choice experiment was conducted to elicit the participants' preferences on the basis of seven attributes with four levels each: efficacy, that is probability of reaching sustained virologic response, treatment duration, treatment convenience (i.e. number of pills and/or injections), gastrointestinal problems, anaemia, dermatological problems and neuropsychological problems. The statistical analysis applied a mixed logit model to estimate preference weights and relative importance scores. RESULTS: Results indicated that the sustained virologic response rate was the most important attribute to participants. Physicians placed an even greater weight on the efficacy of treatments with a relative importance score of 9.33 [95% confidence interval: (6.93-11.91)], as compared with 6.16 [95% confidence interval: (4.34-8.15)] for patients. Neuropsychological problems ranked second for patients and physicians, and were more important to treatment-naive patients than to treatment-experienced patients or physicians. Gastrointestinal problems, anaemia and dermatological problems were of minor importance to all participants. These findings may be explained by the improvement in the management of physical adverse reactions over the last few years, thus making treatment easier to tolerate. CONCLUSIONS: This study is the first conjoint analysis assessing and comparing the preferences of patients and physicians in hepatitis C virus.

A network meta-analysis to compare simeprevir with boceprevir and telaprevir in combination with peginterferon-α and ribavirin in patients infected with genotype 1 Hepatitis C virus.

OBJECTIVE: To conduct a network meta-analysis (NMA) to assess the relative efficacy and safety of simeprevir, a second generation oral protease inhibitor (PI), compared to telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin (PR) in patients with chronic hepatitis C. METHODS: A systematic literature review and NMA of randomized controlled trials involving anti-virals added to PR were conducted. Electronic database searches and hand searches were conducted to identify relevant publications. Outcomes of interest included sustained virologic response (SVR), incidence of adverse events (AEs), and discontinuation due to AEs. Networks were based on treatment-, dose-, and duration-specific nodes. Sub-group analyses were conducted to investigate heterogeneity, based on Metavir scores, sub-genotypes 1a/1b, and prior response. RESULTS: A total of 15 publications were considered for the base case of the meta-analysis. Simeprevir was associated with higher SVR rates than PR alone. Compared to telaprevir and boceprevir, SVR rates tended to be higher for simeprevir, with odds ratios ranging from 1.27 [0.81-2.00] to 2.61 [1.44-4.74] in treatment-naïve and from 1.04 [0.78-1.38] to 1.74 [0.84-3.61] in treatment-experienced patients, respectively. In terms of safety, the risks of anemia and discontinuations due to AEs were lower for simeprevir compared to PR alone, telaprevir, and boceprevir. The risk of rash was lower for simeprevir compared to telaprevir, and similar compared to PR alone and boceprevir. CONCLUSION: This NMA in genotype 1 HCV patients suggests a similar or better efficacy and tolerability profile for simeprevir compared to telaprevir and boceprevir.

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK.

OBJECTIVES: Stroke and TIA are recognized complications of acute herpes zoster (HZ). Herein, we evaluate HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort. METHODS: A retrospective cohort of 106,601 HZ cases and 213,202 controls, matched for age, sex, and general practice, was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, over 24 (median 6.3) years after HZ infection. RESULTS: Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios for TIA and MI but not stroke were increased in all patients with HZ (adjusted hazard ratios [95% confidence intervals]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (adjusted hazard ratios [95% confidence intervals]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], and 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors compared with older patients (p < 0.001). CONCLUSION: HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after HZ infection.

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK.

OBJECTIVES: Stroke and TIA are recognized complications of acute herpes zoster (HZ). In this study, we evaluated HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort. METHODS: A retrospective cohort of 106,601 HZ cases and 213,202 controls matched for age, sex, and general practice was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, up to 24 years (median 6.3 years) after HZ occurrence. RESULTS: Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios (AHRs) for TIA and MI but not stroke were increased in all patients with HZ (AHR [95% confidence interval]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (AHR [95% confidence interval]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors than were older patients (p < 0.001). CONCLUSION: HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after the occurrence of HZ.