Clinical features, therapeutic choice and response by phototype in psoriasis: analysis of the French PsoBioTeq cohort.

BACKGROUND: Little is known about phototype and the response to systemic treatment in psoriasis. OBJECTIVES: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype. METHODS: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index (DLQI) 0/1. RESULTS: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, and more frequently initiated ustekinumab. Patients in the V-VI group maintained the initial biologic prescribed as did the other phototype groups, even though the proportion of patients reaching PASI 90 and DLQI 0/1 at 12 months was lower in this group than the other groups. CONCLUSIONS: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. The phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.

Evolution of Drug Survival with Biological Agents and Apremilast Between 2012 and 2018 in Patients with Psoriasis from the PsoBioTeq Cohort.

Drug survival reflects treatment effectiveness and safety in real life. There is limited data on the variation of drug survival with the availability of systemic treatments with additional biological disease-modifying antirheumatic drugs (bDMARDs) or synthetic disease-modifying antirheumatic drugs (sDMARDs). The aim of this study was to determine whether the increasing number of available systemic treatments for psoriasis affects drug survival over time. Patients were selected from the PsoBioTeq cohort, a French prospective observational cohort enrolling patients with moderate to severe psoriasis. All patients initiating a first bDMARD or sDMARD were included. The primary outcome was comparison of drug survival over time. A multivariate Cox proportional hazard ratio model was computed. A total of 1,866 patients were included; 739 females (39%), median age 47 years. In the multivariate Cox model, no association was found between the calendar year of initiation and drug survival (hazard ratio) overlapping from 0.80 (0.42-1.52) to 1.17 (0.64-2.17), p = 0.633). In conclusion, drug survival in psoriasis is not affected by the year of initiation.

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq.

BACKGROUND: Obesity is associated with an increased risk of psoriasis. OBJECTIVE: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. METHODS: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. RESULTS: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19). CONCLUSION: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.

Benefit-Risk Assessment of Vaccines. Part II: Proposal Towards Consolidated Standards of Reporting Quantitative Benefit-Risk Models Applied to Vaccines (BRIVAC).

INTRODUCTION: Quantitative benefit-risk models (qBRm) applied to vaccines are increasingly used by public health authorities and pharmaceutical companies as an important tool to help decision makers with supporting benefit-risk assessment (BRA). However, many publications on vaccine qBRm provide insufficient details on the methodological approaches used. Incomplete and/or inadequate qBRm reporting may affect result interpretation and confidence in BRA, highlighting a need for the development of standard reporting guidance. OBJECTIVES: Our objective was to provide an operational checklist for improved reporting of vaccine qBRm. METHODS: The consolidated standards of reporting quantitative Benefit-RIsk models applied to VACcines (BRIVAC) were designed as a checklist of key information to report in qBRm scientific publications regarding the assessed vaccines, the methodological considerations and the results and their interpretation. RESULTS: In total, 22 items and accompanying definitions, recommendations, explanations and examples were provided and divided into six main sections corresponding to the classic subdivisions of a scientific publication: title and abstract (items 1-2), introduction (items 3-4), methods (items 5-15), results (items 16-17), discussion (items 18-20) and other (items 21-22). CONCLUSIONS: The BRIVAC checklist is the first initiative providing an operational checklist for improved reporting of qBRm applied to vaccines in scientific articles. It is intended to assist authors, peer-reviewers, editors and readers in their critical appraisal. Future initiatives are needed to provide methodological guidance to perform qBRm while taking into account the vaccine specificities.

Benefit-Risk Assessment of Vaccines. Part I: A Systematic Review to Identify and Describe Studies About Quantitative Benefit-Risk Models Applied to Vaccines.

INTRODUCTION: Understanding the balance between the benefits and risks of vaccination is essential to ensure informed and adequate public health decision making. Quantitative benefit-risk models (qBRm) represent useful tools to help decision makers with supporting benefit-risk assessment throughout the lifecycle of a medical product. However, few initiatives have been launched to harmonise qBRm approaches, specifically for vaccines. OBJECTIVES: The aim of this paper was to identify publications about qBRm applied to vaccines through a systematic literature review, and to describe their characteristics. METHODS: Medline, Scopus and Institute for Scientific Information Web of Knowledge databases were searched to identify articles in English, published from database inceptions up to December 2019. The search strategy included the combination of three key concepts: 'benefit-risk', 'modelling' and 'vaccines'. Data extracted included the modelling context and the methodological approaches used. RESULTS: Of 3172 publications screened, 48 original publications were included. Most of the selected studies were published over the past decade and focused on rotavirus (15), dengue (10) and influenza (6) vaccines. The majority (30) of studies reported analyses related to high-income countries. The methodology of the studies differed, particularly in modelling techniques, benefit-risk measures, and sensitivity analyses. The present work also pointed out a high level of variability in the quality of reporting across studies, with particular regard to input parameters and methodological approaches. CONCLUSIONS: This review provides an extensive list of qBRm applied to vaccines. Discrepancies across studies were identified during our review. While the number of published qBRm studies is increasing, no reporting guidance for qBRm applied to vaccines is currently available. This may affect decision makers' confidence in the results and their benefit-risk assessment(s); therefore, the development of such reporting guidance is highly needed.

Using Discretely Integrated Condition Event Simulation To Construct Quantitative Benefit-Risk Models: The Example of Rotavirus Vaccination in France.

PURPOSE: Although quantitative benefit-risk models (qBRms) are indisputably valuable tools for gaining comprehensive assessments of health care interventions, they are not systematically used, probably because they lack an integrated framework that provides methodologic structure and harmonization. An alternative that allows all stakeholders to design operational models starting from a standardized framework was recently developed: the discretely integrated condition event (DICE) simulation. The aim of the present work was to assess the feasibility of implementing a qBRm in DICE, using the example of rotavirus vaccination. METHODS: A model of rotavirus vaccination was designed using DICE and implemented in spreadsheet software with 3 worksheets: Conditions, Events, and Outputs. Conditions held the information in the model; this information changed at Events, and Outputs were special Conditions that stored the results collected during the analysis. A hypothetical French birth cohort was simulated for the assessment of rotavirus vaccination over time. The benefits were estimated for up to 5 years, and the risks in the 7 days following rotavirus vaccination versus no vaccination were assessed, with the results expressed as benefit-risk ratios. FINDINGS: This qBRm model required 8 Events, 38 Conditions, and 9 Outputs. Two Events cyclically updated the rates of rotavirus gastroenteritis (RVGE) and intussusception (IS) according to age. Vaccination occurred at 2 additional Events, according to the vaccination scheme applied in France, and affected the occurrence of the other Events. Outputs were the numbers of hospitalizations related to RVGE and to IS, and related deaths. The entire model was specified in a small set of tables contained in a 445-KB electronic workbook. Analyses showed that for each IS-related hospitalization or death caused, 1613 (95% credible interval, 1001-2800) RVGE-related hospitalizations and 787 (95% credible interval, 246-2691) RVGE-related deaths would be prevented by vaccination. These results are consistent with those from a published French study using similar inputs but a very different modeling approach. IMPLICATIONS: A limitation of the DICE approach was the extended run time needed for completing the sensitivity analyses when implemented in the electronic worksheets. DICE provided a user-friendly integrated framework for developing qBRms and should be considered in the development of structured approaches to facilitate benefit-risk assessment.

Quantitative Benefit-Risk Models Used for Rotavirus Vaccination: A Systematic Review.

BACKGROUND: Although rotavirus vaccines have proven to prevent the risk of rotavirus gastroenteritis (RVGE) in children under 5 years old, they are also associated with an increased transient risk of intussusception (IS). Several quantitative benefit-risk models (qBRm) are performed to measure this balance in hospitalizations and deaths prevented versus the ones induced. METHOD: In this study, our objective was to provide a complete overview of qBRm used for rotavirus vaccination. We systematically searched 3 medical literature databases to identify relevant articles, in English, that were published between 2006 and 2019. RESULTS: Of the 276 publications screened, 14 studies using qBRm for rotavirus vaccination were retained, based on preselected criteria. Four were performed in low- and middle-income countries. Almost all (13 of 14) displayed the following characteristics: force of infection assumed to be constant over time (static model), indirect effect of rotavirus vaccination (herd effect) not considered, closed model (individuals not allowed to enter and/or exit the model over time), and aggregated level (no tracking of individual's behavior). Most of the models were probabilistic (9 of 14) and reported sensitivity and/or scenario analyses (12 of 14). Input parameter values varied across studies. Selected studies suggest that, depending on the models used, for every IS hospitalization and death induced, vaccination would prevent, respectively, 190-1624 and 71-743 RVGE-related hospitalizations and deaths. CONCLUSIONS: The benefits of rotavirus vaccination were shown to largely exceed the increased risk of IS, across all studies. Future research aiming to harmonize qBRm for rotavirus vaccination should ensure the comparability of studies and provide additional information for regulatory authorities, physicians, and patients.

Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation and Modeling Analysis.

INTRODUCTION: Two vaccines against rotavirus gastroenteritis (RVGE) in young children, Rotarix and RotaTeq, have been available in Europe since 2006. Vaccination against rotaviruses significantly reduces the burden of RVGE, but it is also associated with a very small increased risk of intussusception. In a benefit-risk analysis, the prevented RVGE burden is weighed against the possible excess of intussusception. PURPOSE: The aim was to compare the estimated benefits and risks of Rotarix vaccination in France. METHODS: We estimated the benefits (vaccine-preventable RVGE hospitalizations and deaths) and risks (vaccine-caused intussusception hospitalizations and deaths) following two doses of Rotarix in a birth cohort of 791,183 followed for 3-5 years in France. We used data from peer-reviewed clinical and epidemiological studies or publications, and government statistics. RESULTS: Within the total number of French children below 5 years of age, we estimate vaccination could prevent a median 11,132 [95% credible interval (CI) 7842-14,408] RVGE hospitalizations and 7.43 (95% CI 3.27-14.68) RVGE deaths. At the same time, vaccination could cause an average of 6.86 (95% CI 2.25-38.37) intussusception hospitalizations and 0.0099 (95% CI 0.0024-0.060) intussusception deaths in the entire French birth cohort of infants below 1 year of age. Therefore, for every intussusception hospitalization and every intussusception death caused by vaccination, 1624 (95% CI 240-5243) RVGE hospitalizations and 743 (95% CI 93-3723) RVGE deaths are prevented, respectively, by vaccination. CONCLUSIONS: The vaccine-prevented RVGE hospitalizations and deaths (benefit) greatly outweigh the excess potentially vaccination-related cases of intussusception (risk), indicating a favorable benefit-risk balance for Rotarix in France.