Improvements in Patient-Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real-World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Evaluate patient-reported outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: This analysis includes registry participants who initiated and persisted with on-label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (On-Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient-reported outcomes, including patient-reported pain (0-100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0-100 visual analog scale), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3). Unadjusted, nominal P values were calculated via single-proportion, one-sided test (H0 = 0%; α = 0.05). RESULTS: Of 90 On-Label Persisters, most had treatment-resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease-modifying antirheumatic drugs, respectively), with mean (SD) baseline patient-reported pain, PtGA, and HAQ-DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9 (0.6), respectively. Among those with patient-reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15-mm reductions at 6 months; among those with HAQ-DI scores of at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P < 0.001). CONCLUSION: Pain and physical function are important contributors to health-related quality of life. In this real-world population of patients with treatment-resistant PsA and 6 months of persistent guselkumab treatment, clinically meaningful improvements in pain and physical function were achieved by approximately 40% and 30% of patients, respectively.

Treatment Patterns and Effectiveness of Tofacitinib in Patients Initiating Therapy for Rheumatoid Arthritis: Results From the CorEvitas Rheumatoid Arthritis Registry.

OBJECTIVE: This real-world analysis assessed baseline demographics/characteristics and treatment patterns/effectiveness in patients with rheumatoid arthritis (RA) initiating tofacitinib (TOF) in the US CorEvitas RA Registry. METHODS: The primary analysis of this study included patients with RA initiating TOF with a 12-month follow-up visit from November 2012 to January 2021. Outcomes included baseline demographics/characteristics and TOF initiation/discontinuation reasons, treatment patterns, and effectiveness (disease activity and patient-reported outcomes [PROs] at 12 months); the primary effectiveness outcome was Clinical Disease Activity Index low disease activity (CDAI LDA). All data, analyzed descriptively, were stratified by TOF regimen (monotherapy vs combination therapy), line of therapy (second- to fourth-line), time of initiation (2012-2014, 2015-2017, or 2018-2020), and dose (5 mg twice daily vs 11 mg once daily). RESULTS: Of 2874 patients with RA who initiated TOF, 1298 had a qualifying 12-month follow-up visit; of these, 43.1% were monotherapy and 66.5% were fourth-line therapy. Overall, tumor necrosis factor inhibitors (40.8%) were the most common treatment immediately prior to TOF initiation. The most common reason for TOF initiation (among those with a reason) was lack/loss of efficacy of prior treatment (67.7%). Overall, at 12 months, 31.9% and 10.1% had achieved CDAI LDA and remission, respectively; 22.4%, 10.4%, and 5% had achieved ≥ 20%, ≥ 50%, and ≥ 70% improvement in modified American College of Rheumatology core set measures, respectively; and improvements in PROs were observed. Effectiveness was generally similar across TOF stratifications. CONCLUSION: TOF effectiveness (CDAI LDA) was observed in a US real-world setting of patients with RA regardless of TOF regimen, line of therapy, time of initiation, and dose. (ClinicalTrials.gov: NCT04721808).

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

INTRODUCTION: The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired t tests determined changes that were statistically significantly different from 0 (α = 0.05). RESULTS: Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6 years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was - 5.4 (- 8.5, - 2.3; p < 0.001) at 6 months. Significant mean improvements in PGA (- 19.0 [- 24.2, - 13.8]), patient-reported pain (- 9.1 [- 14.4, - 3.8]), and %BSA (- 5.1 [- 7.6, - 2.7]) were also observed (all p < 0.001). CONCLUSIONS: In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6 months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms. TRIAL REGISTRATION: clinicaltrials.gov: NCT02530268.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study.

Importance: It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. Objective: To assess associations of CA MRI plaque characteristics with incident CVD events. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. Exposures: Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. Main Outcomes and Measures: Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. Results: Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. Conclusions and Relevance: The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Understanding the association between skin involvement and joint activity in patients with psoriatic arthritis: experience from the Corrona Registry.

Objective: To compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity. Methods: Body surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ2 test, Cramer's V) and continuous variables (linear regression). Results: 1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between 21 May 2013 and 20 September 2016 were analysed. Most patients in the BSA >3%/CDAI moderate/high subgroup had worse clinical and patient-reported outcomes. A significant (p<0.001) modest association (Cramer's V=0.1639) between skin severity and joint activity was observed among all patients at enrolment. Patients with higher skin severity were two times more likely to have higher joint involvement (OR 2.27, 95% CI 1.71 to 3.01). A significant linear relationship between CDAI and BSA was observed. Effect modification showed this linear relationship was modified by age, gender, insurance, work status, current therapy, Health Assessment Questionnaire, Nail visual analogue scale, minimal disease activity, dactylitis count, patient-reported pain and fatigue. Conclusion: Skin severity is modestly correlated with joint activity, and patients with higher skin severity are two times more likely to have increased joint involvement. Clinicians need to address both skin severity and joint activity in treatment decisions.

The impact of multiple single day blood pressure readings on cardiovascular risk estimation: The Atherosclerosis Risk in Communities study.

AIMS: The aim of this study was to determine the magnitude of change in estimated cardiovascular disease risk when multiple same day blood pressure measurements are used in estimating coronary heart disease, heart failure and stroke risks. METHODS AND RESULTS: Black and White participants, N = 11,129, enrolled in the Atherosclerosis Risk in Communities study (mean age 53.9 ± 5.7 (SD) years) were included. Each participant had three sitting, five supine, and six standing blood pressure measures during one day. Main outcome measures were changes in estimated coronary heart disease, heart failure and stroke risk when using the different blood pressure measures. Mean sitting, standing and supine systolic blood pressure values of the study population were 120.8 ± 18.6, 124.9 ± 20 and 124.7 ± 19.6 mmHg, respectively. The substitution of the second sitting systolic blood pressure with the third sitting systolic blood pressure (taken ∼5 min later) in two separate coronary heart disease risk models reclassified 3.3% to 5.1% of study participants. Similar substitutions for heart failure and stroke risk prediction models led to reclassification of 1.9% and 2.7% of participants respectively. When mean sitting systolic blood pressure was replaced with mean standing systolic blood pressure 5.4% to 11.6% of the participants were reclassified. Maximum upward and downward change in an individual's estimated risk was 31% and 26% respectively. CONCLUSIONS: Estimated risks of coronary heart disease, heart failure, and stroke for an individual can change significantly within a day due to changes in systolic blood pressure. Given recommendations to use estimated risk for therapeutic decisions, our study has implications for the use of a single systolic blood pressure in cardiovascular risk estimation.

Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study.

OBJECTIVE: To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. APPROACH AND RESULTS: Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non-diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21-1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04-2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. CONCLUSIONS: sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.

Prior preterm birth and maternal subclinical cardiovascular disease 4 to 12 years after pregnancy.

BACKGROUND: We considered that women with prior preterm birth (PTB) would have evidence of subclinical atherosclerosis, endothelial dysfunction, and arterial stiffness. METHODS: Four to 12 years after pregnancy, blood pressure and fasting lipids were analyzed, and women underwent evaluation, following standardized protocols, of carotid intima-media thickness (IMT), brachial flow-mediated dilation (FMD), and pulse wave velocity (PWV). Women with prior preterm (<37 weeks, n=181) or term births (>= 37 weeks, n=306) were compared. Those with preeclampsia or term small-for-gestational-age (SGA) births were excluded. RESULTS: Women with a prior preterm vs. term birth had higher blood pressure, on average, and a more atherogenic lipid profile. They also had marginally higher IMT (0.579 standard error [SE] 0.005-vs. 0.567 [0.004] mm, p=0.06), adjusted for body size, demographics, and smoking. IMT differences were greater among those with non-preeclamptic-indicated PTB (0.034 mm, p=0.05) and PTB<34 weeks (0.024 mm, p=0.04) compared to those with term births. These differences appeared to be explained in part by the atherogenic lipid elevations in women with preterm birth. Women with prior PTB<34 weeks tended to have lower FMD, but results were not statistically significant. PWV did not differ according to PTB. CONCLUSIONS: In the decade following pregnancy, women with non-preeclamptic-indicated PTB or PTB delivered before 34 weeks had higher blood pressure, atherogenic lipids, and IMT compared to women with term births. There may be subgroups of women with a prior PTB with excess cardiovascular risk that is detectable before overt clinical disease.

Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study.

BACKGROUND: Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood and has been associated with cardiovascular disease (CVD) in clinical studies. We assessed the associations between Cp and incident heart failure (HF), death, and CVD in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: Cp was measured at ARIC visit 4 (1996-1998). We studied 9240 individuals without HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide association study was performed to identify genetic determinants of Cp levels and evaluate their association with incident HF in ARIC participants. Cp levels (mean±SD) were higher in women versus men (335±79 versus 258±44 mg/L; P<0.0001), women on versus not on hormone-replacement therapy (398±89 versus 291±60 mg/L; P<0.0001), and African Americans versus whites (299±63 versus 293±74 mg/L; P=0.0005). After adjusting for traditional risk factors, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF (hazard ratio, 1.44; 95% confidence interval, 1.13-1.83) and mortality (hazard ratio, 1.38; 95% confidence interval, 1.11-1.63). A locus on the ceruloplasmin gene on chromosome 3 was significantly associated with Cp levels (normal 295.56±77.60 mg/L; heterozygote 316.72±88.02 mg/L; homozygote 331.04±85.40 mg/L; P=8.3×10(-13)) but not with incident HF. After adjustment for traditional risk factors, Cp levels were also weekly associated with CVD. CONCLUSIONS: Cp was associated with incident HF, mortality, and CVD in the ARIC population. A single locus on chromosome 3 was associated with Cp levels but not with HF.

Prior preterm or small-for-gestational-age birth related to maternal metabolic syndrome.

OBJECTIVE: To estimate whether women who deliver small babies due to preterm birth or growth restriction have excess risk for cardiovascular disease and diabetes later in life. METHODS: Eight years after pregnancy, we estimated the prevalence of metabolic syndrome and its components in a cohort study of women with prior preterm (preterm birth before 37 weeks, n=181) or small for gestational age ([SGA], less than the tenth percentile, n=192) births, compared with women with term births (37 or more weeks, n=306). Women delivered at Magee-Womens Hospital in Pittsburgh, Pennsylvania, and those with preeclampsia or prepregnancy diabetes or hypertension were excluded. Women underwent a structured interview and fasting blood sampling. RESULTS: Women were, on average, 8 years postpartum and 39 years old at evaluation. Women with a prior preterm birth had higher blood pressure, triglycerides, and LDL-cholesterol compared with those in a term control group. Women with prior SGA births were leaner and more likely to smoke compared with those with term births. Women with prior preterm birth had elevated risk of metabolic syndrome, adjusted for demographic, smoking and body size factors (23% preterm compared with 17% control group; odds ratio [OR] 1.76 [1.06, 2.80]). In women with a prior preterm birth, low HDL (11% preterm compared with 5% control group; OR 2.6 [1.2, 5.2]), hypertriglyceridemia (22% compared with 14%; OR 1.9 [1.2, 2.9]), and elevated glucose (24% compared with 19%; OR 1.5 [1.0, 2.3]) accounted for this excess metabolic syndrome. In women with SGA, the only element of metabolic syndrome that was aberrant was glucose metabolism. CONCLUSION: Eight years after pregnancy, women with prior preterm or SGA births had evidence of metabolic syndrome compared with women with term births. Screening and intervention in these women after pregnancy may delay or prevent disease. LEVEL OF EVIDENCE: : II.

Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer.

PURPOSE: Few studies have examined methods of contraception, beyond oral contraceptives (OCs) and tubal ligation, in relation to ovarian cancer risk. METHODS: Nine hundred two cases with incident ovarian/peritoneal/tubal cancer were compared with 1800 population-based control subjects. Women self-reported all methods of contraception by using life calendars. RESULTS: Each of the contraceptive methods examined reduced the risk of ovarian cancer as compared with use of no artificial contraception. Comparing ever versus never use, after adjustment for potentially confounding factors and all other methods of contraception, the methods of contraception that emerged as protective were OCs (adjusted odds ratio [adj OR] 0.75, 95% confidence interval [CI] 0.61-0.93); tubal ligation (adj OR 0.63, 95% CI 0.51-0.77); intrauterine devices (IUDs) (adj OR 0.75, 95% CI 0.59-0.95); and vasectomy (adj OR 0.77, 95% CI 0.61-0.99). Although for OCs and tubal ligation we found that the longer the duration of use, the greater the effect, for IUDs the pattern was reversed: significant protection occurred with short duration and progressively greater risk (albeit nonsignificant) was seen with longer duration of use. CONCLUSIONS: In the largest case-control study to date, a range of effective methods of contraception reduced the risk for ovarian cancer. OCs and tubal ligation reduced ovarian cancer risk with lower odds ratios with longer duration of use, whereas IUDs reduced risk overall, having the greatest impact with short duration of use.