Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis.

INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. METHODS: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. RESULTS: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. CONCLUSION: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. TRIAL REGISTRATION: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

Clinical and demographic factors associated with change and maintenance of disease severity in a large registry of patients with rheumatoid arthritis.

BACKGROUND: We examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA). METHODS: Data from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low (≤10), moderate (>10 and ≤22), and severe (>22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were used to examine impacts of covariates (time between visits, chronological year, disease duration, age) on disease states. RESULTS: Data from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients (46,534 visits) with regular visits (every 3-9 months) were analyzed. The probability of moving from moderate to low or severe disease by next visit was 47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25 months (95% confidence interval: 4.18-4.32). Transition probabilities showed 20% of patients with low disease activity moved to moderate or severe disease within 6 months; >35% of patients with moderate disease remained in moderate disease after 6 months. Results were similar for the regular-visit sub-cohort. Significant interactions with prior disease state were seen with chronological year and disease duration. CONCLUSION: A substantial proportion of patients remain in moderate disease, emphasizing the need for treat-to-target strategies for RA patients.

Perceptions of gender equality in work-life balance, salary, promotion, and harassment: results of the NASPGHAN task force survey.

OBJECTIVES: Gender equality in the workplace has not been described in pediatric gastroenterology. METHODS: An electronic survey that explored perceptions of career parity, work-life balance, and workplace harassment was sent to all members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Reponses were anonymous. RESULTS: Of the 303 respondents (21%), there was an even distribution across geographic region, age, and gender (54% men). Gender affected perception of salary and promotion; 46% of men but only 9% of women feel that "women earn the same as men" (P < 0.001). Similarly, 48% of men but only 12% of women feel that "women rise at the same rate as men" (P < 0.001). Both genders of academic practice respondents, compared with other practice models, perceived men were promoted more quickly than women (P = 0.008). Women had higher dissatisfaction with mentoring than men (29% vs 13%, P = 0.03). Significantly more men than women reported spouses with "flexible jobs" (35% vs 14%, P < 0.001). Having a spouse with "flexible job" or having children (preschool or school age), however, did not affect satisfaction with work-life balance for either gender. Overall, women are more likely to be dissatisfied with work-life balance than men (P = 0.046). CONCLUSIONS: Satisfaction with work-life balance is lower among women versus men pediatric gastroenterologists, but does not correlate with flexibility of spouse's job or caring for young children. Gender-divergent perception of promotion, parity of compensation, and mentoring requires further investigation.

Comparison of body composition assessment methods in pediatric intestinal failure.

OBJECTIVES: The aim of the study was to examine the agreement of multifrequency bioelectric impedance analysis (BIA) and anthropometry with reference methods for body composition assessment in children with intestinal failure (IF). METHODS: We conducted a prospective pilot study in children 14 years or younger with IF resulting from either short bowel syndrome or motility disorders. Bland-Altman analysis was used to examine the agreement between BIA and deuterium dilution in measuring total body water (TBW) and lean body mass (LBM), and between BIA and dual-energy x-ray absorptiometry (DXA) techniques in measuring LBM and fat mass (FM). FM and percent body fat (%BF) measurements by BIA and anthropometry were also compared in relation to those measured by deuterium dilution. RESULTS: Fifteen children with IF, median (interquartile range) age 7.2 (5.0, 10.0) years, and 10 (67%) boys, were studied. BIA and deuterium dilution were in good agreement with a mean bias (limits of agreement) of 0.9 (-3.2 to 5.0) for TBW (L) and 0.1 (-5.4 to 5.6) for LBM (kg) measurements. The mean bias (limits) for FM (kg) and %BF measurements were 0.4 (-3.8 to 4.6) kg and 1.7 (-16.9 to 20.3)%, respectively. The limits of agreement were within 1 standard deviation of the mean bias in 12 of 14 (86%) subjects for TBW and LBM, and in 11 of 14 (79%) for FM and %BF measurements. Mean bias (limits) for LBM (kg) and FM (kg) between BIA and DXA were 1.6 (-3.0 to 6.3) kg and -0.1 (-3.2 to 3.1) kg, respectively. Mean bias (limits) for FM (kg) and %BF between anthropometry and deuterium dilution were 0.2 (-4.2 to 4.6) and -0.2 (-19.5 to 19.1), respectively. The limits of agreement were within 1 standard deviation of the mean bias in 10 of 14 (71%) subjects. CONCLUSIONS: In children with IF, TBW and LBM measurements by multifrequency BIA method were in agreement with isotope dilution and DXA methods, with small mean bias and clinically acceptable limits of agreement. In comparison with deuterium dilution, BIA was comparable to anthropometry for FM and %BF assessments with small mean bias, but the limits of agreement were large. BIA is a reliable method for TBW and LBM assessments in population studies; however, its reliability in individual patients, especially for FM assessments, cannot be guaranteed.

Prevalence and overlap of childhood and adult physical, sexual, and emotional abuse: a descriptive analysis of results from the Boston Area Community Health (BACH) survey.

Abuse is associated with a wide variety of health problems, yet comprehensive population-based data are scant. Existing literature focuses on a single type of abuse, population, or lifestage. Using a racially/ethnically diverse community-based sample, we document the prevalence of physical, emotional, and sexual abuse by lifestage and gender, assess variation in abuse by sociodemographics; establish overlap of abuses; and examine childhood abuse relationships with abuse in adulthood. Prevalence of abuse ranges from 15% to 27%; women report more adulthood emotional abuse and lifetime sexual abuse than men; reports of abuse can vary by race/ethnicity and poverty status, particularly in women; there is overlap between types of abuse; and a history of childhood abuse is associated with a greater risk of abuse as an adult.