Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis.

BACKGROUND: Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab. METHODS: We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline. RESULTS: Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52). DISCUSSION: Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.

Anti-TNF-experienced patients with UC initiating vedolizumab demonstrated higher treatment persistence compared with those initiating tofacitinib in this real-world evaluation of comparative effectiveness. Ultimately, head-to-head randomized trials that focus on directly measured end points are needed to best inform clinical practice.

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease.

INTRODUCTION: Many patients with Crohn's disease (CD) lose response or become intolerant to antitumor necrosis factor (TNF) therapy and subsequently switch out of class. We compared the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse US population of TNF-experienced patients with CD. METHODS: We conducted a retrospective cohort study using longitudinal claims data from a large US insurer (Anthem, Inc.). We identified patients with CD initiating vedolizumab or ustekinumab with anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence for >52 weeks. Secondary outcomes included (i) all-cause hospitalization, (ii) hospitalization for CD with surgery, (iii) hospitalization for CD without surgery, and (iv) hospitalization for infection. Propensity score fine stratification was used to control for demographic and baseline clinical characteristics and prior treatments. RESULTS: Among 885 new users of ustekinumab and 490 new users of vedolizumab, we observed no difference in treatment persistence (adjusted risk ratio 1.09 [95% confidence interval 0.95-1.25]). Ustekinumab was associated with a lower rate of all-cause hospitalization (adjusted hazard ratio 0.73 [0.59-0.91]), nonsurgical CD hospitalization (adjusted hazard ratio 0.58 [0.40-0.83]), and hospitalization for infection (adjusted hazard ratio 0.56 [0.34-0.92]). DISCUSSION: This real-world comparative effectiveness study of anti-TNF-experienced patients with CD initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalizations, nonsurgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We, therefore, advocate for individualized decision making in this medically refractory population, considering patient preference and other factors such as cost and route of administration.

Trajectory Curves for Purposes of Benchmarking and Predicting Clinical Outcomes: A Scoping Review.

Trajectory curves are valuable tools to benchmark patient health status and predict future outcomes. A longitudinal study is underway to examine social participation after burn injury using the Life Impact Burn Recovery Evaluation (LIBRE) Profile with the goal of developing trajectory curves for specific domains that focus on social reintegration. We conducted a scoping review to inform and understand trajectory curves applied in clinical settings to compare outcomes for an individual to a matched cohort of comparable patients or predicted expected outcomes over time. This scoping review utilized a PubMed search from January 2014 to August 2019 for the following terms: "trajectory curves" or "trajectory models" and "clinic" or "clinical." Only articles that specifically referenced longitudinal and clinical research designs were included in the scoping review. Articles were assessed using standard scoping review methods and categorized based on clinical application of trajectory curves for either benchmarking or prediction. The initial literature review identified 141 manuscripts and 34 met initial inclusion criteria. The reviewed articles support the clinical use of trajectory curves. Findings provide insight into several key determinants involved with the successful development and implementation of trajectory curves in clinical settings. These findings will inform efforts to use the LIBRE Profile to model social participation recovery and assist in developing effective strategies using trajectory curves to promote social reintegration after burn injury.

Are burns a chronic condition? Examining patient reported outcomes up to 20 years after burn injury-A Burn Model System National Database investigation.

BACKGROUND: People living with burn injury often face long-term physical and psychological sequelae associated with their injuries. Few studies have examined the impacts of burn injuries on long-term health and function, life satisfaction, and community integration beyond 5 years postinjury. The purpose of this study was to examine these outcomes up to 20 years after burn injury. METHODS: Data from the Burn Model System National Longitudinal Database (1993-2020) were analyzed. Patient-reported outcome measures were collected at discharge (preinjury status recall) and 5 years, 10 years, 15 years, and 20 years after injury. Outcomes examined were the SF-12/VR-12 Physical Component Summary and Mental Component Summary, Satisfaction with Life Scale, and Community Integration Questionnaire. Trajectories were developed using linear mixed models with repeated measures of outcome scores over time, controlling for demographic and clinical variables. RESULTS: The study population included 421 adult burn survivors with a mean age of 42.4 years. Lower Physical Component Summary scores (worse health) were associated with longer length of hospital stay, older age at injury and greater time since injury. Similarly, lower Mental Component Summary scores were associated with longer length of hospital stay, female sex, and greater time since injury. Satisfaction with Life Scale scores decrease negatively over time. Lower Community Integration Questionnaire scores were associated with burn size and Hispanic/Latino ethnicity. CONCLUSION: Burn survivors' physical and mental health and satisfaction with life worsened over time up to 20 years after injury. Results strongly suggest that future studies should focus on long-term follow-up where clinical interventions may be necessary. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Predicting Depression and Posttraumatic Stress Symptoms Following Burn Injury: A Risk Scoring System.

Depression and posttraumatic stress (DPTS) are common psychiatric comorbidities following burn injury. The purpose of this study was to develop an admission scoring system that assesses the risk of development of depression or posttraumatic symptoms in the burn population. This study is a retrospective review of the prospectively collected Burn Model System National Database. Adult burn survivors enrolled from 2014 to 2018 (n = 486) were included. The primary outcome was the presence of DPTS symptoms at 6, 12, or 24 months postinjury. Logistic regression analysis was used to identify demographic and clinical predictors of DPTS symptoms. A risk scoring system was then created based on assigning point values to relevant predictor factors. The study population had a mean age of 46.5 ± 15.8 years, mean burn size of 18.3 ± 19.7%, and was 68.3% male. Prior to injury, 71.3% of the population was working, 47.9% were married, and 50.8% had completed more than a high school education. An 8-point risk scoring system was developed using the following predictors of DPTS symptom development: gender, psychiatric treatment in the past year, graft size, head/neck graft, etiology of injury, and education level. This study is the first to develop a DPTS symptom risk scoring system for burn injury. This scoring system will aid in identifying burn survivors at high risk of long-term psychiatric symptoms that may be used to improve screening, monitoring, timely diagnosis, and interventions.

Burn model system national longitudinal database representativeness by race, ethnicity, gender, and age.

INTRODUCTION: Representativeness of research populations impacts the ability to extrapolate findings. The Burn Model System (BMS) National Database is one of the largest prospective, longitudinal, multi-center research repositories collecting patient-reported outcomes after burn injury. OBJECTIVE: To assess if the BMS Database is representative of the population that is eligible to participate. DESIGN: Data on adult burn survivors who were eligible for the BMS Database from 2015 to 2019 were analyzed. SETTING: Not applicable. PARTICIPANTS: Burn survivors treated at BMS centers meeting eligibility criteria for the BMS Database. Eligibility for the database is based on burn size and receipt of autografting surgery. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Race, ethnicity, gender, and age were compared between individuals who did and did not enroll. Regression analysis examined the correlation between demographic characteristics and study enrollment. Additional regression analysis examined the association between enrollment and the intersection of race, ethnicity, and gender. RESULTS: A total of 982 adult burn survivors were eligible for the BMS database during the study period. Of those who were eligible, 72.1% Enrolled and 27.9% were Not Enrolled. The Enrolled group included more female and more younger survivors compared to the Not Enrolled group. In regression analyses, Black/African American burn survivors were less likely and individuals identifying as female were more likely to enroll in the BMS Database. Furthermore, White men and women were more likely to enroll compared to Black/African American men and women, and non-Hispanic/Latino men were more likely to enroll compared to Hispanic/Latino men. CONCLUSIONS: This study found differences in BMS Database enrollment by race, ethnicity, and gender. Further research is warranted to investigate causes for the disparities found in this study. In addition, strategies are needed to improve enrollment to ensure future representativeness.

Adolescents with and without head and neck burns: comparison of long-term outcomes in the burn model system national database.

INTRODUCTION: Facial burns account for persistent differences in psychosocial functioning in adult burn survivors. Although adolescent burn survivors experience myriad chronic sequelae, little is known about the effect of facial injuries. This study examines differences in long-term outcomes with and without head and neck involvement. METHODS: Data collected for 392 burn survivors between 14-17.9 years of age from the Burn Model System National Database (2006-2015) were analyzed. Comparisons were made between two groups based on presence of a head and neck burn (H&N) using the following patient reported outcome measures: Satisfaction with Appearance Scale, Satisfaction with Life Scale, Community Integration Questionnaire, and Short Form-12 Health Survey at 6, 12, and 24 months after injury. Regression analyses were used to assess association between outcome measures and H&N group at 12-months. RESULTS: The H&N group had more extensive burns, had longer hospital stays, were more likely to be burned by fire/flame and were more likely to be Hispanic compared to the non-H&N group. Regression analysis found that H&N burn status was associated with worse SWAP scores. No significant associations were found between H&N burn status and other outcome measures. CONCLUSIONS: Adolescents with H&N burn status showed significantly worse satisfaction with appearance at 12-months after injury. Future research should examine interventions to help improve body image and coping for adolescent burn survivors with head and neck burns.

"Living Well" After Burn Injury: Using Case Reports to Illustrate Significant Contributions From the Burn Model System Research Program.

The Burn Model System (BMS) program of research has been funded since 1993 by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR). The overarching aim of this program is to improve outcomes and quality of life for people with burns in the areas of health and function, employment, and community living and participation. This review reports on BMS contributions that have affected the lives of individuals with a significant burn injury using case reports to associate BMS contributions with recovery. In January 2020, current BMS grantee researchers assessed peer-reviewed BMS publications from 1994 to 2020. Using case report methodology, contributions were linked to three individuals treated at one of the four Burn Model System institutions. With over 25 years of NIDILRR funding, unique BMS contributions to patient recovery were identified and categorized into one of several domains: treatment, assessment measures, sequelae, peer support, employment, and long-term functional outcomes. A second review for significant results of BMS research that add to the understanding of burn injury, pathophysiology, and recovery research was identified and categorized as injury recovery research. The case study participants featured in this review identified select NIDILRR research contributions as having direct, personal benefit to their recovery. The knowledge generation and clinical innovation that this research program has contributed to our collective understanding of recovery after burn injury is considerable. Using case study methodology with three adult burn survivors, we highlight the impact and individual significance of program findings and reinforce the recognition that the value of any clinical research must have relevance to the lives of the study population.

Sexual activity and romantic relationships after burn injury: A Life Impact Burn Recovery Evaluation (LIBRE) study.

BACKGROUND: Engaging in healthy sexual activity and romantic relationships are important but often neglected areas of post-burn rehabilitation. The degree to which persons with burn injuries engage in sexual activity and romantic relationships is not well understood. This study examined demographic and clinical characteristics predicting engagement in sexual activity and romantic relationships in a sample of adult burn survivors compared to a general United States sample. METHODS: Data for the adult burn survivor sample were from 601 adult burn survivors who participated in field-testing for the calibration of the Life Impact Burn Recovery Evaluation (LIBRE) Profile, a burn-specific instrument assessing social participation on six scales including sexual activity and romantic relationships. Comparison data were obtained from a general population sample of 2000 adults through sample matching. Demographic predictors of sexual activity and romantic relationship status were examined in each sample using modified Poisson regression analyses. Clinical predictors of engaging in sexual activity and romantic relationships were also examined in the LIBRE sample. RESULTS: Participants were slightly more likely to report being sexually active in the adult burn survivor sample than in the general sample (65% vs. 57%, p < 0.01). There was not a significant difference in romantic relationship status between the two samples (64% vs. 62%, p = 0.31). In multivariable regression analyses, men in both samples were more likely to report being in a sexual relationship (RR in LIBRE sample = 1.23, 95% CI 1.08-1.39; RR in general sample = 1.10, 95% CI 1.02-1.18). Participants in both samples who were not working were less likely to report being sexually active or in a romantic relationship (RRs ranging from 0.73 to 0.83, p < 0.05 for all estimates). In the adult burn survivor sample, respondents with hand burns were more likely to report being sexually active and in a romantic relationship (RR = 1.16, 95% CI 1.01-1.33). Time since burn injury, burn size, and burns to other critical areas were not significantly associated with either outcome in adjusted analyses. CONCLUSIONS: The likelihood of engaging in sexual activity and romantic relationships is similar among adult burn survivors and the comparison group representing a general United States sample of adults. Further research addressing sexual activity and romantic relationships after burn injuries will help to foster better patient-clinician dialogue, pinpoint barriers, design interventions, and allocate appropriate resources.

Inhalation injury is associated with long-term employment outcomes in the burn population: Findings from a cross-sectional examination of the Burn Model System National Database.

INTRODUCTION: Inhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury. METHODS: Data collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics. RESULTS: Data from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (p<0.001). Individuals with inhalation injury were less likely to be employed at 24 months post-injury compared to survivors without inhalation injury (OR = 0.63, p = 0.028). There were no significant differences in PCS, MCS, or SWLS scores between groups in adjusted regression analyses. CONCLUSIONS: Burn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms.

Exploring the Burn Model System National Database: Burn injuries, substance misuse, and the CAGE questionnaire.

Burn survivors who misuse alcohol and/other substances have been associated with poorer long-term outcomes and clinical complications following injury. The self-reported CAGE questionnaire (Cut down, Annoyed, Guilty, and Eye-opener) is an outcomes assessment tool used to screen for potential substance misuse. Understanding the persistence and emergence of potential substance misuse through examination of CAGE scores may provide important information about this population. Using data collected from the Burn Model System National Database, demographic and clinical characteristics of individuals who reported positive CAGE scores (total score of ≥2) and those who reported negative CAGE scores (total score of 0 or 1) for either alcohol or other drugs were compared.

An Examination of Follow-up Services Received by Vulnerable Burn Populations: A Burn Model System National Database Study.

While disparities in healthcare outcomes and services for vulnerable populations have been documented, the extent to which vulnerable burn populations demonstrate disparities in long-term care is relatively underexplored. This study's goal was to assess for differences in long-term occupational or physical therapy (OT/PT) and psychological service use after burn injury in vulnerable populations. Data from the Burn Model System National Database (2006-2015) were analyzed. The vulnerable group included participants in one or more of these categories: 65 years of age or older, nonwhite, no insurance or Medicaid insurance, preinjury receipt of psychological therapy or counseling, preinjury alcohol and/or drug misuse, or with a preexisting disability. Primary outcomes investigated were receipt of OT/PT and psychological services. Secondary outcomes included nine OT/PT subcategories. Outcomes were examined at 6, 12, and 24 months postinjury. One thousand one hundred thirty-six burn survivors (692 vulnerable; 444 nonvulnerable) were included. The vulnerable group was mostly female, unemployed at time of injury, and with smaller burns. Both groups received similar OT/PT and psychological services at all time points. Adjusted regression analyses found that while the groups received similar amounts services, some vulnerable subgroups received significantly more services. Participants 65 years of age or older, who received psychological therapy or counseling prior to injury, and with a preexisting disability received more OT/PT and psychological or peer support services at follow-up. Overall, vulnerable and nonvulnerable groups received comparable OT/PT and psychological services. The importance of long-term care among vulnerable subgroups of the burn population is highlighted by this study. Future work is needed to determine adequate levels of follow-up services.