Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases.

INTRODUCTION: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis. RESULTS: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi. CONCLUSIONS: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors. TRIAL REGISTRATION: EU PAS Register ( http://encepp.eu ), identifier #32271.

Longterm, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospective US-based Registry.

OBJECTIVE: To assess longterm safety in a US cohort of patients with rheumatoid arthritis (RA) treated with adalimumab (ADA) in real-world clinical care settings. METHODS: This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry. Patients were adults (≥ 18 yrs) who initiated ADA treatment between January 2008 and June 2017, and who had at least 1 followup visit. RESULTS: In total, 2798 ADA initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean disease duration of 8.3 years. Nearly half (48%) were biologic-naive, and 9% were using prednisone ≥ 10 mg at ADA initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44, 95% CI 2.45-4.84) than in subsequent years, while other measured adverse effects did not vary substantially by duration of exposure. The median time to ADA discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION: Analysis of longterm data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with ADA treatment and provides guidance for physicians prescribing ADA for extended periods.

Discontinuation and switching patterns of tumour necrosis factor inhibitors (TNFis) in TNFi-naive and TNFi-experienced patients with psoriatic arthritis: an observational study from the US-based Corrona registry.

Objective: To examine patterns of tumour necrosis factor inhibitor (TNFi) use in TNFi-naive and TNFi-experienced patients with psoriatic arthritis (PsA) in the USA. Methods: All patients aged ≥18 years with PsA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry who initiated a TNFi (index therapy) between March 2013 and January 2017 and had ≥1 follow-up visit were included. Times to and rates of discontinuation/switch of the index TNFi were compared between TNFi-naive and TNFi-experienced cohorts. Patient demographics and disease characteristics at the time of TNFi initiation (baseline) were compared between cohorts and between patients who continued versus discontinued their index TNFi by the first follow-up visit within each cohort. Results: This study included 171 TNFi-naive and 147 TNFi-experienced patients (total follow-up, 579.2 person-years). Overall, 75 of 171 TNFi-naive (43.9%) and 80 of 147 TNFi-experienced (54.4%) patients discontinued their index TNFi; 33 of 171 (19.3%) and 48 of 147 (32.7%), respectively, switched to a new biologic. TNFi-experienced patients had a shorter time to discontinuation (median, 20 vs 27 months) and were more likely to discontinue (p=0.03) or switch (p<0.01) compared with TNFi-naive patients. Among those who discontinued, 49 of 75 TNFi-naive (65.3%) and 59 of 80 TNFi-experienced (73.8%) patients discontinued by the first follow-up visit; such patients showed a trend towards higher baseline disease activity compared with those who continued. Conclusions: The results of this real-world study can help inform treatment decisions when selecting later lines of therapy for patients with PsA.

One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry.

BACKGROUND: Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias. METHODS: Patients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching. RESULTS: Patients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups.

Risk assessment matters, but only when implemented well: A multisite study in juvenile probation.

There is a strong movement toward juvenile justice agencies' use of risk assessment and risk-need-responsivity approaches to improve case management decisions for young offenders. However, little is known about whether adoption of risk assessment actually effectuates any changes in the way young offenders are handled. This was a multisite study of the impact on case processing of implementation of the Structured Assessment of Violence Risk in Youth (SAVRY) or Youth Level of Service/Case Management Inventory in 6 juvenile probation offices using a prepost design and 1,694 propensity score-matched young offenders. Consistent with the risk principle, there were significant changes to at least some areas of case processing in all but 1 site, most notably with respect to decreases in the amount of supervision youth received and in rates of out-of-home placement. The nature and extent of the impact varied as a function of sites' characteristics and implementation quality, not as a function of the risk assessment used. No increases in recidivism were observed in any site, and there was a significant reduction in recidivism in 1 site. The key benefits of implementation of valid risk assessment and case management procedures were improved resource allocation and fewer instances of inappropriate interference in youths' lives without an apparent increased risk to public safety. (PsycINFO Database Record

Symptom severity of bipolar disorder during the menopausal transition.

BACKGROUND: Little is known about the mood symptom experience of women with bipolar disorder during the menopausal transition (MT). Yet times of rapid hormonal decline, such as the postpartum, are associated with increased risk of severe mood episodes in bipolar disorder, and the MT is a time of increased risk for unipolar depression in women with or without a history of depression. METHODS: Enrollment included 56 women 40-60 years old diagnosed in the bipolar spectrum who were experiencing menopausal symptoms or were up to 5 years since their final menstrual period. Menopausal stages included early menopause, late menopause, or early postmenopause based on standardized criteria. Observational, prospective standardized mood symptom and reproductive hormone assessments were completed periodically. Concurrent menopausal symptoms as well as history of mood exacerbation during past reproductive events were assessed. RESULTS: Forty-four women were included in the main analysis. The average Montgomery-Asberg Depression Rating Scale (MADRS) score was 4.43 points higher in the late transition/early postmenopausal stage women (n = 29) compared to the early menopausal stage women (n = 15) (±SE 2.14; p = 0.039), corresponding to a roughly 10 % higher score (range 0-40) in the late/post stage across all study visits. Results were similar for the Young Mania Rating Scale (YMRS), where the average score was 2.54 points higher in the late/early postmenopausal stage women compared to the early menopausal stage women (±SE 1.15; p = 0.027), also roughly 10 % higher (range 0-26). Estradiol and follicle-stimulating hormone (FSH) absolute levels as well as between-visit change in levels were not notably associated with YMRS or MADRS during study observation. Total Greene Climacteric Symptom (menopausal symptom) score was significantly associated with MADRS but not YMRS. History of mood exacerbation premenstrually and/or postpartum was not significantly associated with YMRS or MADRS severity during the MT. CONCLUSIONS: These results support the theory that times of increased reproductive hormonal changes, such as the late MT and early postmenopause, here compared to early MT, are associated with greater mood symptom severity in bipolar spectrum women. Nonetheless, absolute or change in FSH and estradiol levels were not significantly associated with depression or mood elevation severity.

Does risk assessment make a difference? Results of implementing the SAVRY in juvenile probation.

An effective approach to reducing recidivism is, first, to identify a youth's risk of reoffending and then to match the intensity of interventions to that risk level. This pre-post quasi-experimental, prospective study compared 247 (pre) with 217 (post) adjudicated youths to examine the implementation of the Structured Assessment of Violence Risk in Youth (SAVRY) and its effects on case management practices in Louisiana's Caddo parish probation office. The results indicated that placement rates dropped by 50%, use of maximum levels of supervision dropped by almost 30%, and use of community services decreased except for high-risk youths, but only after the SAVRY was properly implemented. This shift towards more appropriate allocation of resources that are matched to risk level occurred without a significant increase in reoffending. The implications for implementation and for use of risk/needs assessment in juvenile probation are discussed.

Field reliability of the SAVRY with juvenile probation officers: Implications for training.

Two complimentary studies were conducted to investigate the inter-rater reliability and performance of juvenile justice personnel when conducting the Structured Assessment of Violence Risk for Youth (SAVRY). Study 1 reports the performance on four standardized vignettes of 408 juvenile probation officers (JPOs) and social workers rating the SAVRY as part of their training. JPOs had high agreement with the expert consensus on the SAVRY rating of overall risk and total scores, but those trained by a peer master trainer outperformed those trained by an expert. Study 2 examined the field reliability of the SAVRY on 80 young offender cases rated by a JPO and a trained research assistant. In the field, intra-class correlation coefficients were 'excellent' for SAVRY total and most domain scores, and were 'good' for overall risk ratings. Results suggest that the SAVRY and structured professional judgment can be used reliably in the field by juvenile justice personnel and is comparable to reliability indices reported in more lab-like research studies; however, replication is essential.

Development of a measure of the latency to needing a cigarette.

PURPOSE: People addicted to smoking experience a recurrent physiologic need to smoke anytime when they go too long without smoking. Our purpose was to evaluate the reliability and concurrent validity of a measure of the time elapsed between completion of smoking one cigarette and experiencing the need to smoke another (the latency to needing a cigarette-LTNC). We also investigated the relationship between the LTNC and dependence-related symptoms. METHODS: An anonymous, self-administered survey was completed by 134 current adolescent smokers, and in a separate study, 32 smokers were asked to complete a retest. RESULTS: A frequent need to smoke was reported by 84.3% of the current smokers. Consistent with published case histories, the duration of the LTNC varied widely between the individuals. Among subjects who reported a regular need to smoke, 48% reported that their LTNC had shortened over time. The median LTNC among subjects who had smoked <100 cigarettes was 243 hours as compared with 2 hours for those who had smoked ≥ 100 cigarettes (p < .001). Test-retest reliability was reported to be excellent (r = .85, p < .001). As expected, LTNC correlated moderately and inversely with daily cigarette consumption (ρ = -.53, p < .001). It also correlated inversely with cue-induced craving (ρ = -.64, p < .001), psychological reliance on cigarettes (ρ = -.43, p < .001), nicotine withdrawal (ρ = -.57, p < .001), and pleasure obtained from smoking (ρ = -.39, p < .001). CONCLUSION: The data obtained in this study support the reliability and concurrent validity of the LTNC measure.

Family options for parents with mental illnesses: a developmental, mixed methods pilot study.

OBJECTIVE: The objective of this paper is to provide a description of Family Options, a rehabilitation intervention for parents with serious mental illnesses and their children focusing on recovery and resilience, and to report the findings from a pilot study at 6-months post-enrollment for participating mothers. METHODS: A developmental design, and mixed quantitative and qualitative methods facilitate an in-depth understanding of Family Options and its impact on parents early in the implementation process. RESULTS: Participating families faced significant challenges, including long-term mental health conditions in adults, and emotional and behavioral difficulties in children. Data from mothers (n = 22) demonstrate significant improvements in well-being, functioning, and supports and resources at 6 months post-enrollment in Family Options. Mothers report help from Family Options staff consistent with the intervention as conceptualized, and high levels of satisfaction with the intervention as delivered. CONCLUSIONS: Innovative study design and analytic strategies are required to build the evidence base and promote rapid dissemination of effective interventions. Findings from this study will assist purveyors in refining the intervention, and will lay the groundwork for further replication and testing to build the evidence base for parents with serious mental illnesses and their families.

Justice system involvement into young adulthood: comparison of adolescent girls in the public mental health system and in the general population.

We compared arrest onset and frequency and types of charges between a statewide cohort of adolescent girls in the public mental health system and girls of the same age in the general population to investigate important differences that could have policy or intervention implications. Girls in the public mental health system were arrested at earlier ages more frequently and were charged with more serious offenses than were girls in the general population. Our results strongly argue for cooperation between the public mental health and justice systems to provide mental health and offender rehabilitation in their shared population.

Arrests of adolescent clients of a public mental health system during adolescence and young adulthood.

OBJECTIVE: This study examined the relationship of age and gender with risk of arrest among adolescents and young adults who were intensive adolescent users of public mental health services. METHODS: Data were obtained from the Massachusetts Department of Mental Health (DMH) and juvenile and criminal courts. Participants were youths receiving DMH adolescent case management services sometime in 1994-1996 who were born between 1976 and 1979 (781 males and 738 females). They were cross-matched to document arrests between age seven and 25. The study examined age at first arrest, age-specific risk, and the relationship between arrest history and arrest risk by gender and age. RESULTS: Most males (69%) and almost half the females (46%) were arrested by age 25. First arrest was most common before age 18. As in the general population, males' arrest patterns were more concerning than those of females, although patterns were of concern in both groups. Most female arrestees had multiple arrests, many as adults. No gender differences were observed for several factors, including risk of first arrest over age 18. Risk was far greater for those arrested in the previous year than for those never arrested. CONCLUSIONS: Findings justify concerns of public mental health systems regarding justice system involvement of adolescent clients. Risk of first arrest was significant from early adolescence through age 24, indicating a need for arrest prevention into young adulthood. The heightened arrest risk at all ages among those who were recently arrested demarcates a population in need of immediate intervention.