Experience with Tofacitinib in Patients with Ulcerative Colitis: Data from a United States Claims Database.

BACKGROUND: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). AIMS: To evaluate real-world data in US patients with UC receiving tofacitinib. METHODS: Characteristics and outcomes of patients with UC initiating tofacitinib between 2018 and 2019 were assessed using data from the IBM® MarketScan® claims database. The index date was the first tofacitinib claim; pre- and post-index periods were 12 months. Outcomes included tofacitinib adherence/persistence, oral corticosteroid (OCS) use, and healthcare resource utilization (HCRU) and costs. RESULTS: Of 276 patients with UC who initiated tofacitinib, 68 (24.6%) were bio-naïve, and 208 (75.4%) bio-experienced. At month 12, overall median tofacitinib adherence (proportion of days covered) was 0.82 (mean 0.68); 43.8% of patients discontinued tofacitinib (90-day gap). Of patients receiving OCS during the post-index 16-week tapering period, 40.4% discontinued OCS up to 12 months post-index. OCS use decreased in patients continuing tofacitinib versus those discontinuing tofacitinib (29.7% vs 59.5%, respectively). Reductions in all-cause and UC-related outpatient visits were observed for bio-naïve (- 1.34 and - 0.88, respectively) and bio-experienced (- 4.72 and - 5.16, respectively) patients, post-index. Decreased UC-related costs per year were observed for bio-experienced patients (difference in post-index vs pre-index, - US$12,448; driven by changes in pharmacy costs), but not for bio-naïve patients (US$47,152). CONCLUSIONS: In this real-world analysis in a mostly bio-experienced population, the majority of US patients with UC initiating tofacitinib remained on therapy at 12 months, and OCS use was reduced with tofacitinib treatment. HCRU (all patients) and UC-related costs were reduced in bio-experienced patients. The majority of patients with ulcerative colitis starting tofacitinib in this real-world study continued therapy at 12 months; there was a reduction in the use of steroids, and a decrease in healthcare resournce utilization and costs.

Real-world characteristics, treatment experiences and corticosteroid utilisation of patients treated with tofacitinib for moderate to severe ulcerative colitis.

BACKGROUND: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database. METHODS: Patients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation). RESULTS: Among patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3-6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib. CONCLUSIONS: Among patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

High-sensitivity C-reactive protein elevation in patients with prior myocardial infarction in the United States.

IMPORTANCE: The extent to which levels of high-sensitivity C-reactive protein (hs-CRP), a known marker of increased cardiovascular risk, are elevated and are associated with standard cardiovascular risk factors in patients with a history of myocardial infarction (MI) is unknown. OBJECTIVES: To determine the pattern and determinants of the distribution of hs-CRP in those with a prior MI in the United States using a nationally representative sample. DESIGN AND PARTICIPANTS: Adults with hs-CRP data in the National Health and Nutrition Examination Surveys from 1999-2010. RESULTS: Among 1296 individuals in our cohort, the median age was 65 years and the median hs-CRP level was 2.69 mg/L, measured an average of 7.1 years after the MI. Among these patients, 22% had hs-CRP levels of <1 mg/L, 61% had ≥2 mg/L, and 48% had ≥3 mg/L. Increasing hs-CRP was associated in a multivariable model with increasing body mass index (partial R2 [pR2] 0.113, P < .001), increasing non-high-density lipoprotein [HDL] (pR2 0.030, P < .001), increasing age (pR2 0.008, P = .017), and decreasing HDL (pR2 0.005, P = .046). Adjusted mean hs-CRP was also higher in women (3.6 vs 2.7 mg/L; P < .001), in people with hypertension (3.5 vs. 2.8, P = .030), and among smokers (4.2 vs 2.3 mg/L; P < .001), and lower in people with hyperlipidemia (2.8 vs. 3.5, P = .007). Standard cardiovascular risk factors accounted for only 22% of the variability in hs-CRP levels. CONCLUSIONS AND RELEVANCE: Among patients with prior MI, elevated hs-CRP is prevalent several years after the MI, and standard cardiovascular risk factors explain only a small proportion of hs-CRP variability. In light of emerging evidence on the importance of inflammation in the pathogenesis of cardiovascular disease, the high prevalence of elevated hs-CRP in patients with prior MI in the United States may have public health implications.

Development and validation of a risk model for in-hospital worsening heart failure from the Acute Decompensated Heart Failure National Registry (ADHERE).

BACKGROUND: A subset of patients hospitalized with acute heart failure experiences in-hospital worsening heart failure, defined as persistent or worsening signs or symptoms requiring an escalation of therapy. METHODS: We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) >12hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples. RESULTS: We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample (c statistic, 0.74) and validation sample (c statistic, 0.72). CONCLUSIONS: The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure.

Factors associated with variations in hospital expenditures for acute heart failure in the United States.

BACKGROUND: Relatively little contemporary data are available that describe differences in acute heart failure (AHF) hospitalization expenditures as a function of patient and hospital characteristics, especially from a population-based investigation. This study aimed to evaluate factors associated with variations in hospital expenditures for AHF in the United States. METHODS: A cross-sectional analysis using discharge data from the 2011 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, was conducted. Discharges with primary International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes for AHF in adults were included. Costs were estimated by converting Nationwide Inpatient Sample charge data using the Healthcare Cost and Utilization Project Cost-to-Charge Ratio File. Discharges with highest (≥80th percentile) versus lowest (≤20th percentile) costs were compared for patient characteristics, hospital characteristics, utilization of procedures, and outcomes. RESULTS: Of the estimated 1 million AHF hospital discharges, the mean cost estimates were $10,775 per episode. Younger age, higher percentage of obesity, atrial fibrillation, pulmonary disease, fluid/electrolyte disturbances, renal insufficiency, and greater number of cardiac/noncardiac procedures were observed in stays with highest versus lowest costs. Highest-cost discharges were more likely to be observed in urban and teaching hospitals. Highest-cost AHF discharges also had 5 times longer length of stay, were 9 times more costly, and had higher in-hospital mortality (5.6% vs 3.5%) compared with discharges with lowest costs (all P < .001). CONCLUSIONS: Acute heart failure hospitalizations are costly. Expenditures vary markedly among AHF hospitalizations in the United States, with substantial differences in patient and hospital characteristics, procedures, and in-hospital outcomes among discharges with highest compared with lowest costs.

Differences in health care use and outcomes by the timing of in-hospital worsening heart failure.

BACKGROUND: Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. METHODS: Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). RESULTS: Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. CONCLUSION: Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure.

Transient and persistent worsening renal function during hospitalization for acute heart failure.

BACKGROUND: Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. METHODS: We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (< 0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status. RESULTS: Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P < .001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P < .001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P < .001). CONCLUSIONS: Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes.

Retrospective Study of the Prevalence, Predictors, and Consequences of Nonadherence With Lapatinib in Women With Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab.

Background. Lapatinib is an oral small molecule dual tyrosine kinase inhibitor that has been shown to improve time to progression versus capecitabine in women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab. Objective. To describe extent, predictors, and consequences of nonadherence with lapatinib in women with MBC who were previously treated with trastuzumab. Methods. This was a retrospective observational study using data from a large health insurance claims databases spanning January 2000 to March 2010. Measures of lapatinib adherence included medication possession ratio (MPR), time to discontinuation (end of supply), time to first treatment interruption (gap during treatment of 30 days without supply), and duration of continuous therapy (time to gap of 30 days without supply or end of supply). Predictors of nonadherence to lapatinib and the association between nonadherence and outcomes, utilization, and costs were examined using multiple regression analysis. Results. A total of 666 patients met all inclusion criteria. Mean initial lapatinib dosage was 1161 mg daily; 63% received index lapatinib in combination with capecitabine. Mean MPR was 87%; 22% of patients had MPR < 80%. Median time to lapatinib discontinuation was 9.1 months (95% confidence interval = 8.0-10.2). Twenty-seven percent of patients had one or more treatment interruptions during follow-up. Median duration of continuous therapy was 5.9 months (95% confidence interval = 5.1-6.1). Concomitant therapy with a taxane was a predictor of nonadherence (odds ratio for MPR < 80% = 10.30; P < .001). There was a statistically significant association between nonadherence to lapatinib and greater number of outpatient visits (P = .028). Conclusions. In women with MBC who were previously treated with trastuzumab, mean adherence to lapatinib in typical clinical practice is relatively high overall, although there is a small group of patients with high nonadherence. Targeted efforts to improve adherence to lapatinib in this subgroup may be warranted.

1-Year Comparative Effectiveness of Tofacitinib vs Ustekinumab for Patients With Ulcerative Colitis and Prior Antitumor Necrosis Factor Failure.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Real-world data comparing the effectiveness of tofacitinib to ustekinumab are limited. We compared 52-week outcomes of tofacitinib vs ustekinumab for UC after antitumor necrosis factor (anti-TNF) failure. METHODS: In this retrospective cohort study, adults initiated tofacitinib or ustekinumab for UC after anti-TNF failure May 1, 2018 to April 1, 2021, at a US academic medical center. The primary outcome was steroid-free clinical remission (SFCR) at 12 and 52 weeks. The secondary outcome was drug survival (ie, time to drug discontinuation due to nonresponse). Adverse events (AEs) were also assessed. RESULTS: Sixty-nine patients initiated tofacitinib, and 97 patients initiated ustekinumab with median follow-up of 88.0 and 62.0 weeks, respectively. After inverse probability of treatment-weighted logistic and Cox regression, there was no association of tofacitinib vs ustekinumab with SFCR at 12 weeks (odds ratio, 1.65; 95% CI, 0.79-3.41), SFCR at 52 weeks (odds ratio, 1.14; 95% CI, 0.55-2.34), or drug survival (hazard ratio, 1.37; 95% CI, 0.78-2.37). Kaplan-Meier analysis demonstrated no separation in drug survival curves. Regression results were similar after excluding patients with prior tofacitinib or ustekinumab exposure. During available follow-up, 17 AEs were reported for tofacitinib (most commonly shingles, n = 4), and 10 AEs were reported for ustekinumab (most commonly arthralgia and rash, each n = 2). Two patients discontinued treatment due to AEs (1 tofacitinib for elevated liver enzymes, 1 ustekinumab for arthralgia). CONCLUSIONS: In a real-world UC cohort, tofacitinib and ustekinumab demonstrated similar effectiveness at 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

In this real-world cohort of anti-TNF-exposed patients with ulcerative colitis, tofacitinib and ustekinumab demonstrated similar effectiveness in achieving steroid-free clinical remission at 12 and 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

Clinical and Endoscopic Outcomes Through 78 Weeks of Tofacitinib Therapy for Ulcerative Colitis in a US Cohort.

BACKGROUND: Tofacitinib is an oral JAK inhibitor for the treatment of ulcerative colitis (UC). We assessed outcomes through 78 weeks of tofacitinib therapy for UC in a real-world setting. METHODS: This retrospective cohort study included adults initiating tofacitinib for UC from May 1, 2018, to April 1, 2021, at a large academic center in the United States. The primary outcome was steroid-free clinical remission at 78 (+/-4) weeks (SFCR 78; simple clinical colitis activity index ≤2 with no corticosteroid use within 30 days). The secondary outcome was tofacitinib discontinuation due to nonresponse (treatment persistence). Additional outcomes were endoscopic response/remission and adverse events (AEs). RESULTS: Seventy-three patients initiated tofacitinib, with a median follow-up of 88 weeks. Among patients with available data, 31 of 60 (51.7%) achieved SFCR 78, 21 of 47 (44.7%) achieved endoscopic remission during follow-up, and 25 of 73 (34.2%) discontinued tofacitinib during follow-up due to nonresponse (including 11 patients who required colectomy). Nineteen AEs were reported among 15 patients during follow-up: shingles (n = 4, all without documented vaccinations), deep venous thrombosis (n = 2), elevated liver enzymes (n = 2), skin abscess (n = 2), pneumonia (n = 2), possible miscarriage (n = 2), norovirus (n = 1), COVID-19 (n = 1), lymphopenia (n = 1), Clostridioides difficile infection (n = 1), and heart block (n = 1). One patient discontinued therapy due to an AE (elevated liver enzymes), and no deaths occurred. CONCLUSION: Tofacitinib treatment was effective in achieving SFCR for the majority of patients with UC through 78 weeks. Adverse events were consistent with the known safety profile of tofacitinib, and AEs requiring discontinuation were rare. Due to limitations regarding sample size, larger studies are needed to confirm these findings.

Tofacitinib treatment was effective in achieving steroid-free clinical remission for the majority of patients with UC through 78 weeks. Adverse events, which rarely required treatment discontinuation, were consistent with the known safety profile of tofacitinib.

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting.

BACKGROUND: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. METHODS: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors. RESULTS: Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. CONCLUSIONS: In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Previous cesarean section, gestational age at first delivery and subsequent risk of pre-eclampsia in obese mothers.

PURPOSE: We examine the association between prior C-section and subsequent pre-eclampsia; and describe the effect of gestational age at prior C-section, and obesity status on this association. METHODS: The study population included women with two subsequent singleton births in Missouri between 1998 and 2005. The risk for pre-eclampsia/eclampsia was assessed among women with and without prior cesarean delivery. The two groups were followed to their second pregnancy and the occurrence of pre-eclampsia was documented. Additionally, the history of pre-eclampsia, prior cesarean at preterm, and obesity status were examined for their differential effects on the risk of pre-eclamsia. RESULTS: Women with prior C-section were 28% more likely to have pre-eclampsia in their subsequent pregnancy [OR = 1.28; 95% CI = 1.20-1.37]. However, this result was not significant when women with pre-eclampsia in their first pregnancy were excluded. After this exclusion, a more than threefold increased risk for subsequent pre-eclampsia was observed in women with prior early C-section [OR = 3.15; 95% CI= 2.43-4.08], while the level of risk did not change in the prior late C-section group [OR = 0.90; 95% CI= 0.82-1.00]. Subgroup analysis suggested that obesity status modified the risk of prior early C-section but did not affect the risk for prior late C-section. CONCLUSION: Preterm C-section in the first pregnancy may be associated with subsequent pre-eclampsia regardless of prior pre-eclampsia status.

Cost-effectiveness of tofacitinib compared with infliximab, adalimumab, golimumab, vedolizumab and ustekinumab for the treatment of moderate to severe ulcerative colitis in Germany.

OBJECTIVES: Tofacitinib is an oral, small molecule Janus kinase (JAK) inhibitor for the treatment of ulcerative colitis (UC). This study assessed the cost-effectiveness of tofacitinib versus other available treatments for patients with moderate to severe UC following an inadequate response to conventional treatment and who are either naïve to or have failed previous biologics in Germany. METHODS: A Markov cohort model was developed to evaluate the differences in long-term costs and outcomes between tofacitinib and its comparators from the perspective of German statutory health insurance (SHI) for patients either naïve or exposed to biologics. Tofacitinib was compared to infliximab, infliximab biosimilar, adalimumab, adalimumab biosimilar, golimumab, vedolizumab, ustekinumab, and conventional therapy. Health states modeled were remission, treatment response, active UC, and post-colectomy. Patients not responding to treatment could switch to a different treatment. Treatment efficacy for induction and maintenance phases were assessed by a systematic literature review (SLR) and network meta-analysis (NMA). The model included costs associated with drug administration, adverse events, and medical resource use. Extensive deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. RESULTS: Over a life-time horizon, patients treated with tofacitinib gained 0.035-0.083 quality-adjusted life-years (QALYs) and had direct cost savings to the SHI of €4,228-€17,184 compared to biologic treatments other than adalimumab biosimilar. When compared to adalimumab biosimilar, treatment with tofacitinib resulted in an incremental cost-effectiveness ratio (ICER) of €17,497 per QALY gained and can be considered a cost-effective alternative. Compared with conventional therapy, tofacitinib resulted in a lower ICER than all other biologics. The DSA showed that the model results were most influenced by differences in treatment efficacy. The PSA suggested confidence in the base-case results considering uncertainty around parameters. CONCLUSIONS: The results of this economic model suggest tofacitinib is a cost-effective treatment option for patients with moderate to severe UC in Germany.

The impact of body mass index on efficacy and safety in the tofacitinib OCTAVE ulcerative colitis clinical programme.

BACKGROUND: Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. AIMS: To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI). METHODS: This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8-week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (<25, 25 to <30 and ≥30 kg/m2 ). Outcomes included remission, endoscopic improvement, clinical response, sustained steroid-free remission, Inflammatory Bowel Disease Questionnaire total score and Short Form-36 Health Survey scores. Adverse events were evaluated. RESULTS: At Week 8 of OCTAVE Induction 1 and 2, and Week 52 of OCTAVE Sustain, higher proportions of patients receiving tofacitinib 5 or 10 mg twice daily (b.d.) achieved clinical response vs placebo, regardless of baseline BMI subgroup (all P < 0.05). Proportions of patients achieving efficacy endpoints were generally similar across BMI subgroups; in univariate and multivariate regression analyses, BMI was not a significant predictor (all P ≥ 0.05; univariate BMI [continuous] odds ratio for remission: 0.98 [95% confidence interval 0.95, 1.02]). There was no consistent trend between BMI and adverse events. Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other subgroups (0.4%). Limitations included small patient numbers in the BMI ≥30 subgroup. CONCLUSIONS: Efficacy and safety of tofacitinib were similar in patients with UC regardless of baseline BMI.

Comparison of Hydralazine/Nitrate and Angiotensin Receptor Neprilysin Inhibitor Use Among Black Versus Nonblack Americans With Heart Failure and Reduced Ejection Fraction (from CHAMP-HF).

Underuse of hydralazine/nitrate (HYD/NIT) in black patients with heart failure and reduced ejection fraction (HFrEF) has been previously described, but whether this important treatment gap persists in contemporary practice is unknown. Sacubitril/valsartan has become a part of guideline-directed medical therapy for HFrEF but data on utilization of this therapy in black patients is lacking. This study addressed these issues by assessing the frequency of HYD/NIT and sacubitril/valsartan use in black patients with HFrEF in the Change the Management of Patients with Heart Failure Registry, a multicenter cohort study. The association of race with utilization rates of these agents was also evaluated. Clinical and medication data at baseline and during 12 months of follow-up from black and nonblack registry patients without documented contraindications or intolerance to the medications of interest were analyzed. Data were available from December 2015 to October 2017, in 4,848 HFrEF patients, of whom 853 were black (18%) and 3995 were nonblack. Black patients were younger, more likely to be female, and had lower ejection fractions compared with nonblacks. Only 11% of black patients were receiving HYD/NIT therapy at baseline and 13% at 1 year. The percentage of black patients treated at baseline with sacubitril/valsartan was also low at 18% and remained unchanged at 1 year. After adjustment for covariates, race was independently associated with HYD/NIT use (odds ratio 8.32; 95% confidence interval 6.12 to 11.3; p < 0.0001), but not for sacubitril/valsartan. In conclusion, study findings demonstrate a marked persistent treatment gap for HYD/NIT and similar poor utilization of sacubitril/valsartan in black patients with HFrEF despite current guideline recommendations.

Association Between Sacubitril/Valsartan Initiation and Health Status Outcomes in Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: This study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF). BACKGROUND: Although therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown. METHODS: Health status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status. RESULTS: Multivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p < 0.001) over a median (interquartile range [IQR]) of 57 (32 to 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively. CONCLUSIONS: In routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients' symptoms, functions, and quality of life.

Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown. OBJECTIVES: This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes. METHODS: Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up. RESULTS: At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication. CONCLUSIONS: In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.

Target Doses of Heart Failure Medical Therapy and Blood Pressure: Insights From the CHAMP-HF Registry.

OBJECTIVES: This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories. BACKGROUND: Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied. METHODS: Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. <110 mm Hg). RESULTS: Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP <110 mm Hg (n = 674), 17.5% (95% CI: 14.6% to 20.4%; BB), 6.2% (95% CI: 4.4% to 8.1%; ACEI/ARB), and 1.8% (95% CI: 0.8% to 2.8%; ARNI) were receiving target doses. Among those with SBP ≥110 mm Hg (n = 2,421), 19.0% (95% CI: 17.4% to 20.6%; BB), 12.1% (95% CI: 10.8% to 13.4%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.6%; ARNI) were receiving target doses. CONCLUSIONS: In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI, <20% of patients were receiving target doses, even among those with SBP ≥110 mm Hg.

Association of Changes in Heart Failure Treatment With Patients' Health Status: Real-World Evidence From CHAMP-HF.

OBJECTIVES: The aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients' medications with changes in health status. BACKGROUND: Alleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients' health status is unknown. METHODS: The association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression. RESULTS: Among 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p < 0.001). Among patients whose medications were adjusted, 26% had very large clinical improvement (≥20 points) compared with 14% whose regimens were not changed. CONCLUSIONS: In routine care of patients with HFrEF, changes in HFrEF medications were associated with significant improvements in patients' health status, suggesting that health status-based performance measures can quantify the benefits of titrating medicines in patients with HFrEF.