Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.ObjectivesTo evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.MethodsExposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.ResultsA total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.ConclusionIn the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

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FRI0141 CHARACTERIZATION OF SERIOUS INFECTIONS WITH UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2761 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 654-655

Author(s):

K. Winthrop ◽

L. Calabrese ◽

F. Van den Bosch ◽

K. Yamaoka ◽

C. Selmi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Cox Regression ◽

Opportunistic Infections ◽

Oral Candidiasis ◽

Univariate Analysis ◽

Janus Kinase ◽

Research Support ◽

Phase 3 ◽

Increased Risk

Background:Upadacitinib (UPA) is a selective and reversible Janus kinase (JAK) inhibitor with an approved dose of 15 mg once daily (QD) for the treatment of rheumatoid arthritis (RA). Patients (pts) receiving JAK inhibitors have been reported to be at increased risk of developing serious infection events (SIE) and opportunistic infections (OI).Objectives:To evaluate the incidence of SIEs and OIs in pts with RA receiving UPA and active comparators in the Phase 3 SELECT clinical trial program.Methods:The exposure-adjusted event rate (EAER) per 100 patient-years (E/100 PY) of SIEs and OIs was determined in pts receiving UPA in five randomized Phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which four evaluated both UPA 15 mg and 30 mg QD doses and one (SELECT-COMPARE) evaluated only UPA 15 mg QD. Incidences of SIEs and OIs were also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX monotherapy in SELECT-EARLY. Data were analyzed descriptively, with no statistical comparisons between groups or doses. Risk factors for SIEs were determined using a univariate Cox regression model. The data cut-off was June 30, 2019.Results:Overall, 2629 pts who received UPA 15 mg, 1204 pts who received UPA 30 mg, 579 pts who received ADA + MTX, and 314 pts who received MTX monotherapy were included in this analysis. The EAERs (E/100 PYs [95% CI]) of SIEs were 3.2 (2.7–3.7) in the UPA 15 mg group, 5.7 (4.8–6.8) in the UPA 30 mg group, 3.9 (2.6–5.6) in pts receiving ADA + MTX, and 3.1 (1.7–5.2) in pts receiving MTX monotherapy. Pneumonia was the most common SIE, with EAERs (E/100 PYs [95% CI]) of 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.7 (0.2–1.5), and 0.7 (0.1–1.9) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Rates of OIs (including oral candidiasis and disseminated herpes zoster [HZ]) (E/100 PYs [95% CI]) were 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.4 (0.1–1.1), and 0 (0–0) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Oral candidiasis was the most frequent OI with EAERs (E/100 PYs [95% CI]) of 0.4 (0.2–0.6) in the UPA 15 mg group, 0.6 (0.3–1.0) in the UPA 30 mg group, 0.4 (0.1–1.1) in the ADA + MTX group, and 0 (0–0) in the MTX monotherapy group. Serious adverse events of HZ were only reported in the UPA groups (0.2 E/100 PYs [95% CI: 0.1–0.3] and 0.6 E/100 PYs [95% CI: 0.4–1.1] in the UPA 15 mg and 30 mg groups, respectively). Overall, there were 3 (4 coded events), 3, 1, and 0 pts who had active tuberculosis events in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Risk factors for SIEs are shown in the Figure. For both UPA doses, age ≥75 years and smoking were noted to have hazard ratios >1.Conclusion:The incidence rate of SIEs and OIs was higher in the UPA 30 mg group than the UPA 15 mg group. SIEs observed with UPA 15 mg were similar to that seen with ADA although the rates of HZ were higher on UPA. Pts with RA who are ≥75 years old and/or smokers may be at higher risk than other pts with RA for SIEs while receiving UPA.Figure.Univariate analysis of SIE risk factorsDisclosure of Interests:Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Company Ltd, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

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Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 to 2015 and its association with methotrexate, biologics, and corticosteroids

Modern Rheumatology ◽

10.1093/mr/roab026 ◽

2021 ◽

Author(s):

Rei Yamaguchi ◽

Eiichi Tanaka ◽

Ayako Nakajima ◽

Eisuke Inoue ◽

Mai Abe ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Herpes Zoster ◽

Incidence Rate ◽

Medical Records ◽

Cox Regression ◽

Health Assessment ◽

Japanese Version ◽

Cox Regression Analysis ◽

Assessment Questionnaire

ABSTRACT Objectives To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era. Methods We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis. Results Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9–10.5) in total, 6.0 (3.7–9.2) in men, and 11.0 (8.7–13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03–1.26, p < .05), Japanese version of the Health Assessment Questionnaire (J-HAQ) score of 0.5–1.5 (versus J-HAQ = 0; 1.51, 1.09–2.10, p < .05), methotrexate use (1.58, 1.06–2.36, p < .05), and biologic use (1.88, 1.44–2.47, p < .01). Conclusions In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.

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684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.052 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Marrco Vitolo ◽

Vincenzo Livio Malavasi ◽

Marco Proietti ◽

Igor Diemberger ◽

Laurent Fauchier ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Cox Regression ◽

Adverse Outcomes ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Increased Risk ◽

History Of ◽

Cardiac Troponins

Abstract Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P < 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P < 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P < 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

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Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000431311 ◽

2015 ◽

Vol 5 (2) ◽

pp. 286-295 ◽

Cited By ~ 33

Author(s):

Angeliki Tsapanou ◽

Yian Gu ◽

Jennifer Manly ◽

Nicole Schupf ◽

Ming-Xin Tang ◽

...

Keyword(s):

Risk Factors ◽

Daytime Sleepiness ◽

Cox Regression ◽

Sleep Problems ◽

Community Dwelling ◽

Medical Outcomes ◽

Cox Regression Analysis ◽

Incident Dementia ◽

Increased Risk ◽

Sleep Adequacy

Background/Aims: To examine the association between self-reported sleep problems and incidence of dementia in community-dwelling elderly people. Methods: 1,041 nondemented participants over 65 years old were examined longitudinally. Sleep problems were estimated using the RAND Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, sleep short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and risk for incident dementia. Age, gender, education, ethnicity, APOE-ε4, stroke, heart disease, hypertension, diabetes, and depression were included as covariates. Results: Over 3 years of follow-up, 966 (92.8%) participants remained nondemented, while 78 (7.2%) developed dementia. In unadjusted models, sleep inadequacy (‘Get the amount of sleep you need') at the initial visit was associated with increased risk of incident dementia (HR = 1.20; 95% CI 1.02-1.42; p = 0.027). Adjusting for all the covariates, increased risk of incident dementia was still associated with sleep inadequacy (HR = 1.20; 95% CI 1.01-1.42; p = 0.040), as well as with increased daytime sleepiness (‘Have trouble staying awake during the day') (HR = 1.24; 95% CI 1.00-1.54; p = 0.047). Conclusion: Our results suggest that sleep inadequacy and increased daytime sleepiness are risk factors for dementia in older adults, independent of demographic and clinical factors.

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Risk factors for development of second primary malignancies (SPM) after autologous stem cell transplant (ASCT) for multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8038 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8038-8038

Author(s):

Amrita Y. Krishnan ◽

Matthew Mei ◽

Canlan Sun ◽

Jennifer Berano-Teh ◽

Stephen J. Forman ◽

...

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

Cox Regression ◽

Older Age ◽

Second Primary ◽

Cell Transplant ◽

Cox Regression Analysis ◽

Therapeutic Decisions ◽

Increased Risk ◽

Autologous Hct

8038 Background: Studies from the CALGB and IFM have suggested an increased incidence of SPM post ASCT in patients on lenalidomide maintenance. Patients with MM as well as patients post ASCT are inherently at higher risk of SPM. Therefore, assessment of risk factors associated with SPM would be useful in therapeutic decisions re preASCT therapy and post ASCTmaintenance. Methods: We conducted a retrospective cohort study of 841 consecutive MM patients who underwent at least one ASCT at City of Hope from 1989 to 2009. Sixty cases with 70 SPMs were identified. A nested case-control study was also conducted to understand the role of therapeutic exposures associated with SPMs. Controls were MM patients post ASCT matched by year of HCT (±5 years). Results: The median length of follow up was 3.3 yrs. (range 0.3-19.9). Median age at ASCT was 56 yrs (range 18-77). 62% had received a single autologous HCT, 27% tandem autologous HCT, 11% had received multiple HCTs (72 had a second allogeneic HCT)). The overall cumulative incidence of any SPM was 7.4% at 5 years and 15.9% at 10 years; the cumulative incidence of SPMs for patients >55 years approached 21.9% at 10 years. The cumulative incidence of MDS/AML was 1.8% and of solid tumors was 13.0%. Factors examined included age, race, sex, number and individual therapeutic exposures ( pre-ASCT, conditioning, and post-ASCT), disease status at ASCT. Multivariate Cox regression analysis revealed non-Hispanic whites (RR=2.4, 95% CI, 1.2-4.6, p=0.01) and older age (>55) at diagnosis of MM (RR=2.3, 95% CI, 1.3-4.1, p=0.004) to be associated with an increased risk of developing SPMs. Only cumulative thalidomide exposure (both pre-ASCT and post-ASCT) demonstrated a trend toward a positive association (OR=3.5, 95% CI, 0.6-19.4, p=0.15). Six patients (3 cases and 3 controls) were exposed to lenalidomide prior to development of SPM (OR=1.0, 95% CI, 0.14-7.10). Conclusions: This single institution analysis identified non-hispanic whites and older age to be associated with increased risk of developing SPM in pts post ASCT for MM. The trend towards increased risk with thalidomide exposure may be suggestive of a class effect from IMIDs that is not restricted to lenalidomide alone.

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Risk Factors for Atrial Fibrillation following a Cardiac Surgery

10.22541/au.163256940.04888608/v1 ◽

2021 ◽

Author(s):

Ibrahim Marai ◽

Wiaam Khatib ◽

Liza Grosman-Rimon ◽

Shemy Carasso ◽

Ali Sakhnini ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Cardiac Surgery ◽

Cox Regression ◽

Medical Center ◽

Clinical Impact ◽

Cox Regression Analysis ◽

History Of ◽

Vascular Accidents ◽

Preoperative Factors

Background: Atrial fibrillation (AF) following cardiac surgery is common and has clinical impact on morbidity. The preoperative and intraoperative risk factors are still not well defined. The objective of the study was to examine preoperative and intraoperative risk factors for AF following cardiac surgery. Methods: A retrospective analysis of a database of cardiac surgeries was performed during 2017-2019 at Poriya Medical Center. Preoperative factors and intraoperative were recorded. Results: 208 patients were included in this analysis. Overall AF following cardiac surgery was detected in 50 (24%) patients. Of 175 patients who did not have history of AF prior to surgery, 27 (15.5%) had post-operative AF. In the 33 patients with previous AF, AF following surgery was detected in 23 (70%). Patients with AF following surgery who were older (66.2±8.0 vs. 60.7± 11.4 years, p=0.002), were treated more with anti-arrhythmic drugs (18.9% vs 4.5, p<0.001), and had higher rates of pre-operative AF (46% vs 6.3%, p=0.0001), prior cerebral vascular accidents (14% vs 4.4%, p=0.019), and prior valve replacement (10% vs 1.9%, p=0.009) compared to patients without AF following surgery. In multivariate Cox regression analysis, age (HR 1.04, CI 1.01-1.07, P=0.006) and history of preoperative AF (HR 6.01, CI 3.42-10.57, P<0.001) were predictors of AF following cardiac surgery. The probability of being free of postsurgical AF was 80% among patients without history of AF compared to 30% in patients with previous AF history (p<0.001). Conclusion: Preoperative AF and age were predictors of AF following cardiac surgery

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Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review

Clinical Rheumatology ◽

10.1007/s10067-021-05911-4 ◽

2021 ◽

Author(s):

Shunsuke Mori ◽

Fumihiko Ogata ◽

Ryusuke Tsunoda

Keyword(s):

Rheumatoid Arthritis ◽

Diabetes Mellitus ◽

Risk Factors ◽

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Disease Activity ◽

Janus Kinase ◽

Advanced Age ◽

Jak Inhibitors ◽

Increased Risk

AbstractJanus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been raised regarding the risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE). A recent post hoc safety analysis of placebo-controlled trials of JAK inhibitors in rheumatoid arthritis (RA) reported an imbalance in the incidence of VTE for a 4-mg daily dose of baricitinib versus placebo. In a recent postmarketing surveillance trial for RA, a significantly higher incidence of PE was reported in treatment with tofacitinib (10 mg twice daily) compared with tofacitinib 5 mg or tumor necrosis factor inhibitors. We also experienced a case of massive PE occurring 3 months after starting baricitinib (4 mg once daily) for multiple biologic-resistant RA. Nevertheless, the evidence to support the role of JAK inhibitors in VTE risk remains insufficient. There are a number of predisposing conditions and risk factors for VTE. In addition to the known risk factors that can provoke VTE, advanced age, obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking can also contribute to its development. Greater VTE risk is noted in patients with chronic inflammatory conditions, particularly RA patients with uncontrolled disease activity and any comorbidity. Prior to the initiation of JAK inhibitors, clinicians should consider both the number and strength of VTE risk factors for each patient. In addition, clinicians should advise patients to seek prompt medical help if they develop clinical signs and symptoms that suggest VTE/PE. Key Points• Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE), especially those with uncontrolled, high disease activity and those with comorbidities.• In addition to the well-known risk factors that provoke VTE events, advanced age and cardiovascular risk factors, such as obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking, should be considered risk factors for VTE.• Although a signal of VTE/pulmonary embolism (PE) risk with JAK inhibitors has been noted in RA patients who are already at high risk, the evidence is currently insufficient to support the increased risk of VTE during RA treatment with JAK inhibitors.• If there are no suitable alternatives, clinicians should prescribe JAK inhibitors with caution, considering both the strength of individual risk factors and the cumulative weight of all risk factors for each patient.

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The Association Between Serum Leptin Levels and Cardiovascular Events in Patients with Rheumatoid Arthritis

Laboratory Medicine ◽

10.1093/labmed/lmaa037 ◽

2020 ◽

Vol 52 (1) ◽

pp. 86-92 ◽

Cited By ~ 1

Author(s):

Jiliang Chen ◽

Zhiping Xie ◽

Zou Bin

Keyword(s):

Rheumatoid Arthritis ◽

Prognostic Factor ◽

Cox Regression ◽

Univariate Analysis ◽

Elevated Serum ◽

Confounding Factors ◽

Serum Leptin ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Increased Risk

Abstract Objective Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA. Methods Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events. Results The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329–2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019–4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001). Conclusion Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.

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Cardiotoxicity and related risk factors in long-term trastuzumab (T) administration for metastatic breast cancer (MBC): A retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11616 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11616-e11616

Author(s):

Barbara Pistilli ◽

Andrea Marcellusi ◽

Michele Valeri ◽

Umberto Torresi ◽

Dania Nacciarriti ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Cardiac Disease ◽

Cox Regression ◽

Significant Risk ◽

Concomitant Chemotherapy ◽

Cox Regression Analysis ◽

Significant Difference ◽

History Of

e11616 Background: Continuing T beyond progression has become a common strategy in the treatment of human epidermal growth receptor 2- overexpressing (HER2) MBC. However, T administered for several years with concomitant chemotherapy elicits concern about cardiac safety especially in patients (pts) with risk factors. Methods: Cardiac events (CEs) and survival of HER2 MBC pts treated with T +/- chemotherapy at our institution from Dec 2003 to Jun 2012 were evaluated. CEs were graded by NCI-CTCAE v 3.0. Risk factors assessed for cardiotoxicity were: age, body mass index, antihypertensive therapy, history of cardiac disease, diabetes, hypothyroidism, smoking, prior radiotherapy on the chest wall, prior cumulative dose of anthracycline(A), interval between last A dose and first T dose, baseline LVEF, continued/interrupted T exposure, concomitant chemotherapy. Chi-square test was used to compare distribution of CEs over different times of T exposure (p≤ 0.05). Univariate and multivariate Cox regression analysis were used to assess the effect of risk predictors. Results: Sixty-two pts assessable. Median age 52 years (range, 29 to 76), median cumulative time receiving T 29.5 months (range, 3 to 99 months); 40 pts (64.5%) received T without interruption and 19 pts (30.6%) were treated for more than 36 months. CEs occurred in 11 out of all pts (17.7%): grade 1 in 3 pts (4.8%), grade 2 in 5 (8.1%) and grade 3 in 3 (4.8%). The rate of CEs showed no statistically significant difference in pts receiving T for up to 36 months and over: 7/43 (16.3%) and 4/19 (21%), respectively, (p =0.724). In univariate Cox regression analysis significant risk factors were: history of cardiac disease (HR 6,814, 95% CI: 1,384-33,542) and smoking (HR 5,228, 95% CI: 1,403-19,491). In multivariate analysis smoking was the only independent predictor (HR 5,886, 95% CI: 1,479-23,247). Median survival from MBC diagnosis was 50 months (range, 6 to 101 months). Conclusions: Despite the limited sample size, our analysis suggests that cardiotoxicity does not hamper a long-term use of T, since the rate of CEs did not increase in pts treated over 36 months. Moreover, smoking appears to be a predictive factor of T cardiotoxicity.

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The impact of parental risk factors on the risk of stroke in type 1 diabetes

Acta Diabetologica ◽

10.1007/s00592-021-01694-x ◽

2021 ◽

Author(s):

Anni Ylinen ◽

◽

Stefanie Hägg-Holmberg ◽

Marika I. Eriksson ◽

Carol Forsblom ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Hemorrhagic Stroke ◽

Cox Regression Analysis ◽

Parental Risk Factors ◽

Increased Risk ◽

History Of ◽

The Impact

Abstract Background Individuals with type 1 diabetes have a markedly increased risk of stroke. In the general population, genetic predisposition has been linked to increased risk of stroke, but this has not been assessed in type 1 diabetes. Our aim was, therefore, to study how parental risk factors affect the risk of stroke in individuals with type 1 diabetes. Methods This study represents an observational follow-up of 4011 individuals from the Finnish Diabetic Nephropathy Study, mean age at baseline 37.6 ± 11.9 years. All strokes during follow-up were verified from medical records or death certificates. The strokes were classified as either ischemic or hemorrhagic. All individuals filled out questionnaires concerning their parents’ medical history of hypertension, diabetes, stroke, and/or myocardial infarction. Results During a median follow-up of 12.4 (10.9–14.2) years, 188 individuals (4.6%) were diagnosed with their first ever stroke; 134 were ischemic and 54 hemorrhagic. In Cox regression analysis, a history of maternal stroke increased the risk of hemorrhagic stroke, hazard ratio 2.86 (95% confidence interval 1.27–6.44, p = 0.011) after adjustment for sex, age, BMI, retinal photocoagulation, and diabetic kidney disease. There was, however, no association between maternal stroke and ischemic stroke. No other associations between parental risk factors and ischemic or hemorrhagic stroke were observed. Conclusion A history of maternal stroke increases the risk of hemorrhagic stroke in individuals with type 1 diabetes. Other parental risk factors seem to have limited impact on the risk of stroke.

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