Real-world effectiveness of risankizumab in patients with moderate-to-severe psoriasis using the CorEvitas Psoriasis Registry.

BACKGROUND: Psoriasis, an inflammatory skin disease, is often treated with biologic therapeutics. OBJECTIVE: To determine the real-world treatment effectiveness of risankizumab, an interleukin-23 inhibitor, in the treatment of moderate-to-severe plaque psoriasis. METHODS: A retrospective, observational study was conducted using the CorEvitas Psoriasis Registry for eligible adults with a diagnosis of moderate-to-severe psoriasis and persistent use of risankizumab at 12 (±3) months after initiation. Skin clearance measures and patient-reported outcomes were analyzed for the entire study population and by prior biologic treatment. RESULTS: Among 287 patients with persistent risankizumab use at 1 year, most achieved clear or clear/almost clear skin and reported significant reductions in Dermatology Life Quality Index scores, psoriasis symptoms (fatigue, skin pain, and overall itch), and work and activity impairment. LIMITATIONS: The CorEvitas Psoriasis Registry is not necessarily representative of all adults with psoriasis in the United States and Canada and does not measure patient adherence. CONCLUSION: Patients treated with risankizumab, regardless of prior treatment, achieved high levels of clear and clear/almost clear skin, Dermatology Life Quality Index scores of 0/1, and significant reductions in psoriasis symptoms (fatigue, skin pain, and overall itch) and work and activity impairment 1 year after initiation.

The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Characteristics of Patients with Crohn's Disease With or Without Perianal Fistulae in the CorEvitas Inflammatory Bowel Disease Registry.

BACKGROUND: There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD). AIM: To describe characteristics of patients with CD with and without perianal fistulae. METHODS: In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none). RESULTS: Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3 years; difference 4.3 years; 95% CI, 2.0, 6.6) and fewer had Harvey-Bradshaw Index scores indicative of remission (0-4, 56.8% vs 69.6%; difference - 12.9%; 95% CI, - 21.6, - 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vs 58.4%; difference 17.7%; 95% CI, 10.1, 25.4), and surgeries (59.4% vs 27.7%; difference 31.7%; 95% CI, 23.3, 40.1), and a history of treatment with tumor necrosis factor inhibitors (81.3% vs 60.7%; difference 20.6%; 95% CI, 13.5, 27.7), immunosuppressants (51.6% vs 31.2%; difference 20.4%; 95% CI, 11.9, 29.0), and antibiotics (50.3% vs 23.7%; difference 26.6%; 95% CI, 18.2, 35.1) than patients without perianal fistulae. CONCLUSIONS: Patients with CD with current/previous perianal fistulae have more symptomatic experiences of disease, higher medication use, hospitalization rates, and emergency room visits than patients without perianal fistulae. Interventions to prevent/reduce risk of developing fistulae may help improve outcomes in CD.

Meaningful Improvement and Worsening in Patients Who Do Not Achieve Low Disease Activity and Switch Therapy to a New Biologic or Targeted Disease-Modifying Antirheumatic Drug: Results From the CorEvitas RA Registry.

OBJECTIVE: The aim of this study was to assess the change in disease activity associated with switching from 1 biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to another in patients with rheumatoid arthritis who did not achieve low disease activity (LDA) after 6 to 12 months of their initial treatment. METHODS: This observational study included patients from the CorEvitas Rheumatoid Arthritis Registry, who initiated a b/tsDMARD at the index visit (prebaseline), had any clinical disease activity index (CDAI) improvement but did not achieve LDA/remission at the subsequent visit (baseline), and switched therapy at baseline or between baseline and follow-up visits. Regardless of the preswitch CDAI value, 2 thresholds of CDAI change were used to define meaningful improvement and worsening for all patients: ≥6 units and ≥12 units; no meaningful change was defined as any change between -6 to +6 units and -12 to +12 units, based on respective thresholds. RESULTS: Of 1226 patients fulfilling the inclusion criteria, 93 (7.6%) switched therapy at baseline or between baseline and follow-up, after an inadequate response at the baseline visit. At follow-up, meaningful worsening occurred in 30.1% and 12.9% of switchers, whereas the remaining switchers achieved meaningful improvement (34.4% and 20.4%) or had no meaningful change (35.5% and 66.7%), based on the thresholds of ≥6 and ≥12 units, respectively. CONCLUSIONS: Rheumatoid arthritis patients, who had not achieved LDA and switched b/tsDMARD, were more likely to have meaningful improvement or no change, rather than meaningful worsening. These data may help some patients overcome their hesitancy to switch therapy, potentially improving clinical outcomes.

Persistent Opioid Use After Combat Injury and Subsequent Long-term Risk of Abuse: A Retrospective Cohort Study.

OBJECTIVE: To determine whether persistent opioid use after injury is associated with subsequent long-term development of clinically recognized opioid abuse. SUMMARY BACKGROUND DATA: Opioid abuse is an epidemic in the United States and trauma can initiate persistent use; however, it remains unclear whether persistent opioid use contributes to the subsequent development of opioid abuse. The care of combat casualties by the Departments of Defense and Veterans Affairs uniquely allows investigation of this long-term outcome. METHODS: This retrospective cohort study randomly selected 10,000 battle-injured United States military personnel. We excluded patients who died during initial hospitalization or within 180 days of discharge, had a preinjury opioid abuse diagnosis, or had missing data in a preselected variable. We defined persistent opioid use as filling an opioid prescription 3 to 6 months after discharge and recorded clinically recognized opioid abuse using relevant diagnosis codes. RESULTS: After exclusion, 9284 subjects were analyzed, 2167 (23.3%) of whom developed persistent opioid use. During a median follow-up time of 8 years, 631 (6.8%) patients developed clinically recognized opioid abuse with a median time to diagnosis of 3 years. Injury severity and discharge opioid prescription amount were associated with persistent opioid use after trauma. After adjusting for patient and injury-specific factors, persistent opioid use was associated with the long-term development of clinically recognized opioid abuse (adjusted hazard ratio, 2.39; 95% confidence interval, 1.99-2.86). CONCLUSIONS: Nearly a quarter of patients filled an opioid prescription 3 to 6 months after discharge, and this persistent use was associated with long-term development of opioid abuse.

Traumatic injury and atrial fibrillation among deployed service members.

INTRODUCTION: Atrial fibrillation and atrial flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history. METHODS: Sampled from the Department of Defense (DoD) Trauma Registry (n = 10,000), each injured patient in this retrospective cohort study was matched with a non-injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD-9-CM and ICD-10-CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL. RESULTS: There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non-injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non-injured patients (hazards ratio [HR] = 2.04; 95% confidence interval [CI] = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR = 1.51; 95% CI = 0.99, 2.52). CONCLUSION: Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular-related covariates. These findings highlight the need for combat casualty surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms.

The Enduring Health Consequences of Combat Trauma: a Legacy of Chronic Disease.

BACKGROUND: A better understanding of the long-term health effects of combat injury is important for the management of veterans' health in the Department of Defense (DoD) and Veterans Affairs (VA) health care systems and may have implications for primary care management of civilian trauma patients. OBJECTIVE: To determine the impact of traumatic injury on the subsequent development of hypertension (HTN), diabetes mellitus (DM), and coronary artery disease (CAD) after adjustment for sociodemographic, health behavior, and mental health factors. DESIGN: Retrospective cohort study of current and former US military personnel with data obtained from both the DoD and VA health care systems. PARTICIPANTS: Combat injured (n = 8727) service members between 1 February 2002 and 14 June 2016 randomly selected from the DoD Trauma Registry matched 1:1 based on year of birth, sex, and branch of service to subjects that deployed to a combat zone but were not injured. MAIN MEASURES: Traumatic injury, stratified by severity, compared with no documented injury. Diagnoses of HTN, DM, and CAD defined by International Classification of Diseases 9th or 10th Revision Clinical Modification codes. KEY RESULTS: After adjustment, severe traumatic injury was significantly associated with HTN (HR 2.78, 95% CI 2.18-3.55), DM (HR 4.45, 95% CI 2.15-9.18), and CAD (HR 4.87, 95% CI 2.11-11.25), compared with no injury. Less severe injury was associated with HTN (HR 1.14, 95% CI 1.05-1.24) and CAD (HR 1.62, 95% CI 1.11-2.37). CONCLUSIONS: Severe traumatic injury is associated with the subsequent development of HTN, DM, and CAD. These findings have profound implications for the primary care of injured service members in both the DoD/VA health systems and may be applicable to civilian trauma patients as well. Further exploration of pathophysiologic, health behavior, and mental health changes after trauma is warranted to guide future intervention strategies.

Rhabdomyolysis among Critically Ill Combat Casualties: Long-Term Outcomes.

BACKGROUND: Although rhabdomyolysis has been associated with acute kidney injury and mortality in the short term, the long-term consequences of an episode of rhabdomyolysis remain unknown. We sought to identify the long-term outcomes of rhabdomyolysis, including mortality, renal function, and incidence of hypertension (HTN), among service members initially admitted to the intensive care unit after sustaining a combat injury in Iraq or Afghanistan between February 1, 2002 and February 1, 2011. METHODS: Information on age, sex, injury severity score, mechanism of injury, serum creatinine, burn injury, presenting mean arterial pressure, and creatine kinase were retrospectively collected and analyzed for 2,208 patients. Standard descriptive tests were used to compare characteristics of patients with and without rhabdomyolysis. Competing risk Cox proportional hazards models were performed to assess the associated risk of rhabdomyolysis with both HTN and poor renal function. RESULTS: While rhabdomyolysis was associated with HTN on univariate analysis (hazard ratio [HR] 1.30, 95% CI 1.03-1.64; p = 0.029), this difference did not persist on multivariable analysis (HR 1.27, 95% CI 0.99-1.62; p = 0.058). The median estimated glomerular filtration rate (eGFR) was 119 (interquartile range [IQR] 103-128) among those with rhabdomyolysis, compared with 108 (IQR 94-121) in the group without rhabdomyolysis (p < 0.001). CONCLUSION: After adjustment, patients with rhabdomyolysis were not at an increased risk of HTN compared to patients without rhabdomyolysis. eGFR was paradoxically higher in patients with rhabdomyolysis. There was no association found between rhabdomyolysis and mortality.

U.S. military service and the prevalence of metabolic syndrome: Findings from a cross-sectional analysis of the Cooper Center Longitudinal Study, 1979-2013.

U.S. military service confers both health benefits and risks potentially associated with a clustering of cardiovascular risk factors called metabolic syndrome. However, the association between prior military service and metabolic syndrome has not sufficiently been examined. The purpose of the study was to compare the prevalence of metabolic syndrome by prior military service status. Among 42,370 men (887 with prior military service) examined from 1979 to 2013 at the Cooper Clinic (Dallas, TX), we used a cross-sectional study design to examine the association between military service and metabolic syndrome. First, an unadjusted log binomial regression model was performed by regressing the prevalence of metabolic syndrome on prior service. This was followed by performing Kleinbaum's modeling strategy for assessing confounding. The same methodology was used to explore the association between individual metabolic syndrome risk factors and prior service. Prior military service was not significantly associated with the prevalence of metabolic syndrome (PR=0.98, 0.89-1.07). None of the variables explored were identified as confounders. Participants with prior military service had lower prevalence of both elevated levels of triglycerides (PR=0.89, 0.80-0.99) and low levels of high-density lipoprotein-cholesterol (PR=0.78, 0.70-0.88). They had a higher prevalence of elevated resting systolic blood pressure (PR=1.23, 1.12-1.35). However, none of these associations were significant after adjusting for identified confounders: age; cardiorespiratory fitness; and exam year. Study findings indicate that military service was not independently associated with the prevalence of metabolic syndrome or its components. Future research is warranted longitudinally assessing the impact of military service on long-term outcomes.

Completion of Multidisciplinary Treatment for Persistent Postconcussive Symptoms Is Associated With Reduced Symptom Burden.

OBJECTIVE: To investigate the pre- to posttreatment changes in both posttraumatic stress disorder (PTSD) and persistent postconcussive symptoms (PPCSs). SETTING AND PARTICIPANTS: We studied 257 active-duty patients with a history of mild traumatic brain injury (mTBI) who completed multidisciplinary outpatient treatment at Brooke Army Medical Center TBI Clinic from 2008 to 2013. This treatment program included cognitive rehabilitation; vestibular interventions; headache management; and integrated behavioral healthcare to address co-occurring psychiatric conditions such as PTSD, depression, and sleep disturbance. DESIGN: A 1-group; preexperimental, pre- to posttreatment study. MAIN MEASURES: The Neurobehavioral Symptom Inventory (NSI) was used to assess PPCSs, and the PTSD Checklist-Military Version (PCL-M) was used to asses PTSD symptoms. RESULTS: Global PPCS resolution (mean NSI: 35.0 pre vs 23.8 post; P < .0001; d = 0.72) and PTSD symptom resolution (mean PCL-M: 43.2 pre vs 37.7 post; P < .0001; d = 0.34) were statistically significant. Compared with those with only mTBI, patients with mTBI and PTSD reported greater global PPCS impairment both pretreatment (mean NSI: 48.7 vs 27.9; P < .0001) and posttreatment (mean NSI: 36.2 vs 17.4; P < .0001). After adjusting for pretreatment NSI scores, patients with comorbid PTSD reported poorer PPCS resolution than those with mTBI alone (mean NSI: 27.9 pre vs 21.7 post; P = .0009). CONCLUSION: We found a reduction in both self-reported PPCSs and PTSD symptoms; however, future studies are needed to identify specific components of care associated with symptom reduction.

Prevalence of Cardiovascular and Cancer Risk Factors Among Rheumatoid Arthritis Patients Prescribed Janus Kinase Inhibitors and Tumor Necrosis Factor Inhibitors: A Cross-Sectional Study.

OBJECTIVE: The study was to determine the prevalence of baseline risk factors for cardiovascular outcomes and cancer among commercially-insured patients with rheumatoid arthritis (RA) during their first dispensed treatment for either tumor necrosis factor inhibitors (TNFi) or JAK inhibitors (JAKi). METHODS: Patients with RA from August 16, 2019 to March 31, 2022 were identified in the Merative MarketScan Commercial and Medicare databases. The first date that a TNFi or JAKi was dispensed was the index date, and baseline risk factors were assessed among patients continuously eligible for 12 months before the index date. Patients who had the following were stratified into an elevated risk category: age ≥65 years, smoking, or a history of a major adverse cardiovascular event, venous thromboembolism, or cancer. The prevalence of modifiable risk factors was also reported: hypertension, hyperlipidemia, obesity, and diabetes. The crude prevalence and prevalence difference (PD) were reported. RESULTS: A total of 12,673 patients (TNFi [n = 7,748; 61%] and JAKi [n = 4,925; 39%]) met inclusion criteria. The prevalence of elevated risk was the same for all patients using TNFi (n = 2,051; 26%) and JAKi (n = 1,262; 26%). Compared with patients having low risk, patients with an elevated risk also had a higher prevalence of at least one primary modifiable risk factor for both patients using JAKi (79% vs 58%; PD 21%, 95% confidence interval [CI] 18%-24%) and TNFi (81% vs 60%; PD 21%, 95% CI 19%-23%). CONCLUSION: In recent years, JAKi and TNFi were used in similar proportions to treat RA among commercially-insured patients at elevated cardiovascular and cancer risk. Because uncontrolled disease, modifiable comorbidities, and treatment with JAKi are associated with these adverse events, future studies evaluating how practice patterns may be affected by the emergence of safety data will be of value.

Comparison of Racial and Ethnic Mortality Disparities among Post-9/11 Veterans with and without Traumatic Brain Injury to the Total U.S. Adult Population.

INTRODUCTION: The extent of racial/ethnic disparities and whether they are attenuated in the Veteran population compared to the total US population is not well understood. We aimed to assess racial/ethnic mortality disparities from all-cause, cardiovascular (CVD) and cancer among post-9/11 military Veterans with and without exposure to TBI, compared to the total US population. METHODS: This cohort study included 2,502,101 US military Veterans (18,932,083 person-years) who served after 09/11/2001 with 3 or more years of care in the Military Health System (MHS); or had 3 or more years of care in the MHS and 2 or more years of care in the Veterans Health Administration. Mortality follow-up occurred from 01/01/2002 to 12/31/2020. Mortality rate ratios (MRR) from negative binomial regression models were reported for racial/ethnic groups compared to White non-Hispanic Veterans for all-cause, CVD and cancer mortality. Veteran MRR were compared to the total US population. RESULTS: Mortality rates for Black Non-Hispanic Veterans were higher for all-cause (MRR = 1.21;95%CI: 1.13-1.29; p < 0.001), CVD (MRR = 1.78;95%CI: 1.62-1.96; p < 0.001) and cancer (MRR = 1.17;95%CI: 1.10-1.25; p < 0.001) than in White Non-Hispanic Veterans. Among Veterans with TBI, only Black Non-Hispanics had higher mortality than White Non-Hispanics and only for CVD (MRR = 1.32;95%CI: 1.12-1.54; p < 0.001), while CVD mortality was higher among Veterans without TBI (MRR = 1.77;95%CI: 1.63-1.93;p < 0.001). MRR for Black Non-Hispanics in the total US population, were consistently higher than those in the Veteran population for all-cause (MRR = 1.52;95%CI: 1.46-1.58; p < 0.001), CVD (MRR = 2.03;95%CI: 1.95-2.13; p < 0.001) and cancer (MRR = 1.26;95%CI: 1.22-1.30; p < 0.001). CONCLUSION: This Veteran cohort experienced less racial/ethnic disparity in mortality than the total US population, especially among Veterans with TBI.

Advancing Combat Casualty Care Statistics and Other Battlefield Care Metrics.

Aggregate statistics can provide intra-conflict and inter-conflict mortality comparisons and trends within and between U.S. combat operations. However, capturing individual-level data to evaluate medical and non-medical factors that influence combat casualty mortality has historically proven difficult. The Department of Defense (DoD) Trauma Registry, developed as an integral component of the Joint Trauma System during recent conflicts in Afghanistan and Iraq, has amassed individual-level data that have afforded greater opportunity for a variety of analyses and comparisons. Although aggregate statistics are easily calculated and commonly used across the DoD, other issues that require consideration include the impact of individual medical interventions, non-medical factors, non-battle-injured casualties, and incomplete or missing medical data, especially for prehospital care and forward surgical team care. Needed are novel methods to address these issues in order to provide a clearer interpretation of aggregate statistics and to highlight solutions that will ultimately increase survival and eliminate preventable death on the battlefield. Although many U.S. military combat fatalities sustain injuries deemed non-survivable, survival among these casualties might be improved using primary and secondary prevention strategies that prevent injury or reduce injury severity. The current commentary proposes adjustments to traditional aggregate combat casualty care statistics by integrating statistics from the DoD Military Trauma Mortality Review process as conducted by the Joint Trauma System and Armed Forces Medical Examiner System.

United States Military Fatalities During Operation Inherent Resolve and Operation Freedom's Sentinel.

BACKGROUND: Military operations provide a unified action and strategic approach to achieve national goals and objectives. Mortality reviews from military operations can guide injury prevention and casualty care efforts. METHODS: A retrospective study was conducted on all U.S. military fatalities from Operation Inherent Resolve (OIR) in Iraq (2014-2021) and Operation Freedom's Sentinel (OFS) in Afghanistan (2015-2021). Data were obtained from autopsy reports and other existing records. Fatalities were evaluated for population characteristics; manner, cause, and location of death; and underlying atherosclerosis. Non-suicide trauma fatalities were also evaluated for injury severity, mechanism of death, injury survivability, death preventability, and opportunities for improvement. RESULTS: Of 213 U.S. military fatalities (median age, 29 years; male, 93.0%; prehospital, 89.2%), 49.8% were from OIR, and 50.2% were from OFS. More OIR fatalities were Reserve and National Guard forces (OIR 22.6%; OFS 5.6%), conventional forces (OIR 82.1%; OFS 65.4%), and support personnel (OIR 61.3%; OFS 33.6%). More OIR fatalities also resulted from disease and non-battle injury (OIR 83.0%; OFS 28.0%). The leading cause of death was injury (OIR 81.1%; OFS 98.1%). Manner of death differed as more homicides (OIR 18.9%; OFS 72.9%) were seen in OFS, and more deaths from natural causes (OIR 18.9%; OFS 1.9%) and suicides (OIR 29.2%; OFS 6.5%) were seen in OIR. The prevalence of underlying atherosclerosis was 14.2% in OIR and 18.7% in OFS. Of 146 non-suicide trauma fatalities, most multiple/blunt force injury deaths (62.2%) occurred in OIR, and most blast injury deaths (77.8%) and gunshot wound deaths (76.6%) occurred in OFS. The leading mechanism of death was catastrophic tissue destruction (80.8%). Most fatalities had non-survivable injuries (80.8%) and non-preventable deaths (97.3%). CONCLUSIONS: Comprehensive mortality reviews should routinely be conducted for all military operation deaths. Understanding death from both injury and disease can guide preemptive and responsive efforts to reduce death among military forces.

Long-Term Health Care Costs for Service Members Injured in Iraq and Afghanistan.

INTRODUCTION: Over the last two decades, the conflicts in Iraq and Afghanistan have cost the United States significantly in terms of lives lost, disabling injuries, and budgetary expenditures. This manuscript calculates the differences in costs between veterans with combat injuries vs veterans without combat injuries. This work could be used to project future costs in subsequent studies. MATERIALS AND METHODS: In this retrospective cohort study, we randomly selected 7,984 combat-injured veterans between February 1, 2002, and June 14, 2016, from Veterans Affairs Health System administrative data. We matched injured veterans 1:1 to noninjured veterans on year of birth (± 1 year), sex, and first service branch. We observed patients for a maximum of 10 years. This research protocol was reviewed and approved by the David Grant USAF Medical Center institutional review board (IRB), the University of Utah IRB, and the Research Review Committee of the VA Salt Lake City Health Care System in accordance with all applicable Federal regulations. RESULTS: Patients were primarily male (98.1% in both groups) and White (76.4% for injured patients, 72.3% for noninjured patients), with a mean (SD) age of 26.8 (6.6) years for the injured group and 27.7 (7.0) years for noninjured subjects. Average total costs for combat-injured service members were higher for each year studied. The difference was highest in the first year ($16,050 compared to $4,135 for noninjured). These differences remained significant after adjustment. Although this difference was greatest in the first year (marginal effect $12,386, 95% confidence interval $9,736-$15,036; P < 0.001), total costs continued to be elevated in years 2-10, with marginal effects ranging from $1,766 to $2,597 (P < 0.001 for all years). More severe injuries tended to increase costs in all categories. CONCLUSIONS: Combat injured patients have significantly higher long-term health care costs compared to their noninjured counterparts. If this random sample is extrapolated to the 53,251 total of combat wounded service members, it implies a total excess cost of $1.6 billion to date after adjustment for covariates and a median follow-up time of 10 years. These costs are likely to increase as injured veterans age and develop additional chronic conditions.

Suicide attempts and mental health diagnoses in combat-injured service members: A retrospective cohort study.

INTRODUCTION: Examinations of risk factors for suicide attempt in United States service members at high risk of mental health diagnoses, such as those with combat injuries, are essential to guiding prevention and intervention efforts. METHODS: Retrospective cohort study of 8727 combat-injured patients matched to deployed, non-injured patients utilizing Department of Defense and Veterans Affairs administrative records. RESULTS: Combat injury was positively associated with suicide attempt in the univariate model (HR = 1.75, 95% CI 1.5-2.1), but lost significance after adjustment for mental health diagnoses. Utilizing Latent Transition Analysis in the combat-injured group, we identified five mental/behavioral health profiles: (1) Few mental health diagnoses, (2) PTSD and depressive disorders, (3) Adjustment disorder, (4) Multiple mental health comorbidities, and (5) Multiple mental health comorbidities with alcohol use disorder (AUD). Multiple mental health comorbidities with AUD had the highest suicide attempt rate throughout the study and more than four times that of Multiple mental health comorbidities in the first study year (23.4 vs. 5.1 per 1000 person years, respectively). CONCLUSION: Findings indicate that (1) combat injury's impact on suicide attempt is attenuated by mental health and (2) AUD with multiple mental health comorbidities confers heightened suicide attempt risk in combat-injured service members.

Clinical Outcomes in Patients with Rheumatoid Arthritis After Switching Between Interleukin-6-Receptor Inhibitors and Janus Kinase Inhibitors: Findings from an Observational Study.

INTRODUCTION: This observational study evaluated response in patients with rheumatoid arthritis (RA) who switched from an interleukin-6 receptor inhibitor (IL-6Ri) to a Janus kinase inhibitor (JAKi) and vice versa. METHODS: Adult patients with RA, who initiated IL-6Ri or JAKi (following discontinuation of JAKi or IL-6Ri, respectively) during/after December 2012 and had a 6-month follow-up visit were enrolled. Clinical outcomes were evaluated at baseline and the follow-up visit. Continuous outcomes included Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count, swollen joint count, Physician Global Assessment (MDGA), Patient Global Assessment (PtGA), and morning stiffness duration. Categorical outcomes included the proportion of patients achieving CDAI low disease activity (LDA), remission, and minimal clinically important differences (MCIDs) for HAQ, pain, fatigue, MDGA, and PtGA. Continuous outcomes were summarized as mean changes from baseline, and categorical outcomes as response rates. Differences in the outcome measures between groups were evaluated using linear and logistic regression models. RESULTS: Between IL-6Ri (n = 100) and JAKi initiators (n = 129), no significant differences were noted for continuous outcomes. Within both groups, a significant proportion of patients achieved LDA, remission, and MCIDs for other measures, although the odds of achieving LDA were higher among IL-6Ri (vs. JAKi) initiators with moderate-to-severe disease (adjusted odds ratio: 3.30 [1.01, 10.78]). CONCLUSIONS: Patients with RA can achieve improvement in response when switching between IL-6Ri and JAKi. Although both therapies affect the IL-6 pathway, there are distinct mechanisms of action, which likely contribute to their clinical improvement, when reciprocally switched as follow-on treatments.

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry.

OBJECTIVE: Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. METHODS: Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. RESULTS: Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). CONCLUSION: This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population.

Association of Traumatic Brain Injury With Mortality Among Military Veterans Serving After September 11, 2001.

Importance: Emerging evidence suggests that harmful exposures during military service, such as traumatic brain injury (TBI), may contribute to mental health, chronic disease, and mortality risks. Objective: To assess the mortality rates and estimate the number of all-cause and cause-specific excess deaths among veterans serving after the September 11, 2001, terrorist attacks (9/11) with and without exposure to TBI. Design, Setting, and Participants: This cohort study analyzed administrative and mortality data from January 1, 2002, through December 31, 2018, for a cohort of US military veterans who served during the Global War on Terrorism after the 9/11 terrorist attacks. Veterans who served active duty after 9/11 with 3 or more years of care in the Military Health System or had 3 or more years of care in the Military Health System and 2 or more years of care in the Veterans Health Administration were included for analysis. The study used data from the Veterans Affairs/Department of Defense Identity Repository database, matching health records data from the Military Health Service Management Analysis and Reporting tool, the Veterans Health Administration Veterans Informatics and Computing Infrastructure, and the National Death Index. For comparison with the total US population, the study used the Centers for Disease Control and Prevention WONDER database. Data analysis was performed from June 16 to September 8, 2021. Exposure: Traumatic brain injury. Main Outcomes and Measures: Multivariable, negative binomial regression models were used to estimate adjusted all-cause and cause-specific mortality rates for the post-9/11 military veteran cohort, stratified by TBI severity level, and the total US population. Differences in mortality rates between post-9/11 military veterans and the total US population were used to estimate excess deaths from each cause of death. Results: Among 2 516 189 post-9/11 military veterans (2 167 736 [86.2%] male; and 45 324 [1.8%] American Indian/Alaska Native, 160 178 [6.4%], Asian/Pacific Islander, 259 737 [10.3%] Hispanic, 387 926 [15.4%] non-Hispanic Black, 1 619 834 [64.4%] non-Hispanic White, and 43 190 [1.7%] unknown), 17.5% had mild TBI and 3.0% had moderate to severe TBI; there were 30 564 deaths. Adjusted, age-specific mortality rates were higher for post-9/11 military veterans than for the total US population and increased with TBI severity. There were an estimated 3858 (95% CI, 1225-6490) excess deaths among all post-9/11 military veterans. Of these, an estimated 275 (95% CI, -1435 to 1985) were not exposed to TBI, 2285 (95% CI, 1637 to 2933) had mild TBI, and 1298 (95% CI, 1023 to 1572) had moderate to severe TBI. Estimated excess deaths were predominantly from suicides (4218; 95% CI, 3621 to 4816) and accidents (2631; 95% CI, 1929 to 3333). Veterans with moderate to severe TBI accounted for 33.6% of total excess deaths, 11-fold higher than would otherwise be expected. Conclusions and Relevance: This military veteran cohort experienced more excess mortality compared with the total US population than all combat deaths from 9/11/01 through 9/11/21, concentrated among individuals exposed to TBI. These results suggest that a focus on what puts veterans at risk for accelerated aging and increased mortality is warranted.