scholarly journals Subsequent Primary Malignancies Among Myelodysplastic Syndrome Patients Treated with or without Lenalidomide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 413-413 ◽  
Author(s):  
Dana E Rollison ◽  
Kenneth H. Shain ◽  
Ji-Hyun Lee ◽  
Shalaka S Hampras ◽  
Kate Fisher ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Myelodysplastic Syndrome ◽  
Stock Options ◽  
Research Funding ◽  
Case Control ◽  
Cancer Center ◽  
Control Analysis ◽  
Increased Risk ◽  
Nested Case Control ◽  
Disease Specific

Abstract Introduction: Lenalidomide is approved by the FDA for treatment of transfusion-dependent, lower risk, deletion 5q (del(5q)) MDS patients and used widely in practice for non-del(5q) MDS patients with anemia. Recently, subsequent primary malignancies (SPM) have been reported to be associated with lenalidomide treatment of multiple myeloma, and it is unclear if this observation is disease-specific or more broadly related to a particular therapy. The SPM risk in lenalidomide-treated MDS patients has not been evaluated previously. To investigate whether lenalidomide is associated with an increased risk of SPM in MDS patients, we conducted a large, retrospective cohort study of 1,248 MDS patients treated with or without lenalidomide at the Moffitt Cancer Center (MCC). Methods: Patients treated for MDS at MCC in 2004-2012 were identified through MCC's enterprise wide data warehouse which combined clinical information from a variety of sources, including the Cancer Registry, electronic medical records and disease-specific databases. A total of 1,248 MDS patients, ages 18+ years, were identified, corresponding to International Classification of Diseases for Oncology Third Edition (ICD-O-3) codes 99801, 99803, 99833, 99843, 99853, 99863, 99873, 99891 and 99893. A total of 41 cases of SPM were verified by two hematologists for confirmation of both the baseline MDS diagnosis and the SPM diagnosis. SPM incidence rates were estimated based on the Poisson distribution. Cox proportional hazards ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the age-adjusted association between lenalidomide treatment and SPM in the overall cohort, and stratified by lower versus higher risk IPSS. To obtain additional details on lenalidomide treatment and potential confounders, medical chart abstraction was conducted for all SPM cases in addition to a sample of MDS patients from the baseline cohort who had not developed SPM; these controls were matched to cases 1:1 on age at MDS diagnosis (<60 versus 60+ years), gender, follow-up time (+/- 6 months), date of diagnosis, (+/- 1 year), lower versus higher risk IPSS, and presence or absence of del (5q). Based on the medical record data abstracted for the nested case-control sample, associations between lenalidomide and SPM were estimated using odds ratios (OR) and 95% CI's calculated through conditional logistic regression, with adjustment for age at diagnosis, use of erythroid-stimulating agents (ESA), use of azacitidine and MDS histology. Results: Overall, 1,248 MDS patients were followed for an average of 30 months, including patients treated with (n=210) or without (n=1,038) lenalidomide. Incident SPM's were observed for 5 patients treated with lenalidomide (0.7 per 100 person-years) and 36 patients treated without lenalidomide (1.4 per 100 person-years), corresponding to an age-adjusted HR of 0.53 (95% CI=0.21-1.36) (Figure 1). Of the 41 SPM's observed, 33 were solid tumors comprised of 15 types, and 8 were hematological malignancies other than AML; no differences in SPM risk were observed by type of SPM. When stratified by IPSS, there was no increased risk of SPM observed for patients with low risk or intermediate-1 MDS (HR=0.36, 95% CI=0.11-1.20) nor for patients with intermediate-2 and high risk MDS (HR=2.30, 95% CI=0.45-11.65). Of the 41 SPM cases and 41 matched controls included in the nested case-control analysis, 12.2% (n=5) and 29.3% (n=12) were treated with lenalidomide, respectively, corresponding to an adjusted OR of 0.03 (95% CI=0.01-0.63). Similar associations were observed for lenalidomide whether given as part of first line treatment or subsequent therapy, and for lenalidomide given alone or in combination with other drugs. Conclusion: To our knowledge this is the first report to address rate of SPM among MDS patients treated with lenalidomide. SPM was not associated with lenalidomide treatment among a large cohort of patients with a broad spectrum of MDS diagnoses. Figure 1: Incidence of subsequent primary malignancies (SPM) among patients treated for myelodysplastic syndrome (MDS) with or without lenalidomide, Moffitt Cancer Center 2004-2012 Figure 1:. Incidence of subsequent primary malignancies (SPM) among patients treated for myelodysplastic syndrome (MDS) with or without lenalidomide, Moffitt Cancer Center 2004-2012 Disclosures Rollison: Celgene, Inc.: Research Funding. Off Label Use: Lenalidomide for the treatment of non-del(5q) MDS and/or multiple myeloma. Shain:Envision/Celgene: Research Funding, Speakers Bureau; L&M Healthcare/Onyx/Amgen: Research Funding, Speakers Bureau. Lee:Celgene, Inc.: Research Funding. Hampras:Celgene, Inc: Research Funding. Fisher:Celgene, Inc: Research Funding. Al Ali:Celgene, Inc: Research Funding. Padron:Icyte: Speakers Bureau; Novartis: Speakers Bureau. Lancet:Celgene: Consultancy, Research Funding. Olesnyckyj:Celgene: Employment, stock options Other. Kenvin:Celgene: Employment, stock options Other. Knight:Celgene, Inc: Employment, stock options Other. Dalton:Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene, Inc.: Research Funding. List:Celgene, Inc.: Consultancy. Komrokji:Celgene: Consultancy, Research Funding.

scholarly journals Subsequent Primary Malignancies Among Multiple Myeloma Patients Treated with or without Lenalidomide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2129-2129 ◽  
Author(s):  
Dana E Rollison ◽  
Rami Komrokji ◽  
Ji-Hyun Lee ◽  
Shalaka S Hampras ◽  
William Fulp ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stock Options ◽  
Research Funding ◽  
Case Control ◽  
Cancer Center ◽  
Control Analysis ◽  
Increased Risk ◽  
Case Control Analysis ◽  
Nested Case Control

Abstract Introduction: The incidence of subsequent primary malignancies (SPM) associated with lenalidomide treatment of multiple myeloma (MM) outside the context of maintenance therapy post-melphalan is unknown. Three clinical trials reported modest, statistically significant increased risks of SPM associated with lenalidomide treatment in MM patients (Palumbo et al, N Engl J Med, 2012; Attal et al, N Engl J Med, 2012; McCarthy et al, N Engl J Med, 2012). Although these randomized trials are well controlled for potential confounders, they represent a unique population of patients and a specific juxtaposition of lenalidomide use with melphalan; as such, their results are not necessarily generalizable to the broader MM patient population. To investigate whether lenalidomide is associated with an increased risk of SPM in MM patients within a clinical setting in the United States, we conducted a retrospective cohort study of 1,653 MM patients treated with or without lenalidomide at the Moffitt Cancer Center (“MCC”) in Tampa, FL. Methods: Patients treated for MM at MCC from 2004-2012 were identified through Moffitt's enterprise wide data warehouse combining clinical information from several sources, including the Cancer Registry, electronic medical records and disease-specific databases. Among 1,653 MM patients, ages 18 and older, 51 cases of SPM were verified by two hematologists for confirmation of MM and SPM diagnoses. Incidence rates and 95% confidence intervals (CI) for SPM were estimated using a Poisson distribution. Cox proportional hazards ratios (HR) and 95% CIs were calculated to estimate the age-adjusted association between lenalidomide treatment and SPM in the overall cohort, and stratified by ISS. Additional details on lenalidomide treatment and potential confounders were obtained through medical chart abstraction for SPM cases and a subset of MM patients from the baseline cohort who had not developed SPM; these controls were matched to cases 2:1 on age at MM diagnosis (+/- 5 years), gender, follow-up time (+/- 6 months), and date of diagnosis (+/- 1 year). Associations between lenalidomide and SPM in the nested case-control analysis were estimated using odds ratios (OR) and 95% CIs adjusted for age at MM diagnosis, bone marrow transplantation, creatinine levels and personal history of cancer. Results: Overall, 1,653 MM patients were followed for an average of 40 months, including patients treated with (n=846) or without (n=807) lenalidomide. Incident SPMs were observed for 15 patients treated with lenalidomide (0.55 per 100 person-years) and 36 patients treated without lenalidomide (1.27 per 100 person-years), corresponding to an HR of 0.44 (95% CI=0.24-0.80) (Figure 1). Of the 51 SPMs observed, 37 were solid tumors comprising 14 different types, including 9 and 28 in the lenalidomide and no lenalidomide groups, respectively (HR=0.55, 95% CI=0.15-0.69). Of the 14 hematological SPMs observed, 8 were in the lenalidomide group versus 6 in the no lenalidomide group (HR=0.90, 95%CI = 0.31-2.63). Similar associations between lenalidomide and SPM were observed for MM patients with ISS = 1 (HR=0.26, 95% CI=0.06-1.21) and for MM patients with ISS = 2 or 3 (HR=0.20, 95% CI=0.02-1.62). Of the 51 SPM cases and 102 matched controls included in the nested case-control analysis, 33.3% and 74.5% were treated with lenalidomide, respectively (adjusted OR=0.03, 95% CI=0.002-0.34). Similar associations were observed for lenalidomide given as part of first line treatment versus subsequent treatment, and for lenalidomide given alone or in combination with other drugs. (8 cases and 46 controls received melphalan in addition to lenalidomide.) There was no association between lenalidomide and SPM among those treated for >9.1 months (OR=0.05, 95% CI=0.01-0.43), the median treatment duration among controls. Conclusion: Lenalidomide treatment was not associated with an increased risk of SPM among a large cohort of MM patients. It is important to note that in this clinical setting (in 2004-2012) the use of lenalidomide in combination with melphalan and in the maintenance setting was a rare event. This may be a critical factor in the contrast between the results of this study and in the increase in SPMs reported in randomized clinical trials. Figure 1: Incidence of SPM among patients treated for MM with or without lenalidomide, Moffitt Cancer Center, 2004-2012 Figure 1:. Incidence of SPM among patients treated for MM with or without lenalidomide, Moffitt Cancer Center, 2004-2012 Disclosures Rollison: Celgene, Inc.: Research Funding. Off Label Use: Lenalidomide given as treatment for non-del(5q) MDS and/or multiple myeloma . Komrokji:Celgene: Consultancy, Research Funding. Lee:Celgene, Inc.: Research Funding. Hampras:Celgene, Inc: Research Funding. Fulp:Celgene, Inc.: Research Funding. Fisher:Celgene, Inc: Research Funding. Baz:Celgene: Research Funding; BMS: Research Funding; Millenium: Research Funding; Sanofi: Research Funding; Karyopharm: Research Funding. Olesnyckyj:Celgene: Employment, stock options Other. Kenvin:Celgene: Employment, stock options Other. Knight:Celgene, Inc: Employment, stock options Other. Dalton:Celgene, Inc.: Research Funding; Novartis: Consultancy, Honoraria; Genentech: Consultancy, Honoraria. Shain:L&M Healthcare/Onyx/Amgen: Research Funding, Speakers Bureau; Envision/Celgene: Research Funding, Speakers Bureau.

scholarly journals Lenalidomide and Risk of Acute Myeloid Leukemia (AML) Transformation Among Myelodysplastic Syndrome (MDS) Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1912-1912
Author(s):  
Dana E Rollison ◽  
Kenneth H. Shain ◽  
Ji-Hyun Lee ◽  
Shalaka S Hampras ◽  
William Fulp ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Research Funding ◽  
Case Control ◽  
Myelogenous Leukemia ◽  
Cancer Center ◽  
Control Analysis ◽  
Increased Risk ◽  
Case Control Analysis

Abstract Introduction: Lenalidomide is currently approved by the FDA for treatment of transfusion-dependent, lower risk, deletion 5q (del(5q)) MDS patients. In practice, lenalidomide is often used for treatment of non-del(5q) anemic, lower risk MDS patients as endorsed by national guidelines. The risk of AML transformation among non-del(5q) MDS patients treated with lenalidomide has not been well studied, nor among del(5q) MDS patients outside the context of original clinical trials. We conducted a retrospective cohort study of 1,248 MDS patients treated with or without lenalidomide at the Moffitt Cancer Center (MCC) to investigate the association between lenalidomide and AML transformation. Methods: Patients treated for MDS at MCC in 2004-2012 were identified through MCC's data warehouse, including data from the Cancer Registry, electronic medical records and disease-specific databases. A total of 1,248 MDS patients, ages 18+ years, were identified, corresponding to International Classification of Diseases for Oncology Third Edition (ICD-O-3) codes 99801, 99803, 99833, 99843, 99853, 99863, 99873, 99891 and 99893. A total of 150 cases of AML transformation were verified by two hematologists confirming the MDS diagnosis and AML transformation. Incidence rates and 95% confidence intervals (CI) for AML transformation were estimated based on the Poisson distribution. Cox proportional hazards ratios (HR) and 95% CIs were calculated to estimate age-adjusted associations between lenalidomide treatment and AML transformation in the overall cohort, and stratified by lower (low and intermediate-1) risk versus higher (intermediate-2 and high) risk IPSS. To obtain additional details on lenalidomide treatment and potential confounders, medical chart abstraction was conducted for all AML cases and a sample of MDS patients from the baseline cohort who had not developed AML; these controls were matched to cases 1:1 on age at MDS diagnosis (<60 versus 60+ years), gender, follow-up time (+/- 6 months), date of diagnosis, (+/- 1 year), lower versus higher risk IPSS, and presence or absence of del (5q). Based on the abstracted data for the nested case-control sample, associations between lenalidomide and AML transformation were adjusted for cytogenetic risk, use of erythroid-stimulating agents (ESA), percent bone marrow myeloblasts, and MDS histology. Results: Overall, 1,248 MDS patients were followed for an average of 30 months, including patients treated with (n=210) or without (n=1,038) lenalidomide. AML transformation was observed among 16 patients treated with lenalidomide (2.4 per 100 person-years) and 134 patients treated without lenalidomide (5.5 per 100 person-years), corresponding to an age-adjusted HR of 0.44 (95% CI=0.26-0.74). Only two of the 150 MDS patients who transformed to AML had MDS del(5q). When stratified by IPSS, there was no increased risk of AML transformation associated with lenalidomide among patients with lower risk IPSS (HR=0.27, 95% CI=0.12-0.64) or patients with higher risk IPSS (HR=0.99, 95% CI=0.51-1.93). Based on the nested case-control analysis, 16.0% and 20.7% of MDS-AML cases and matched MDS controls who did not develop AML were treated with lenalidomide, respectively, corresponding to an adjusted odds ratio (OR) of 1.16 (95% CI=0.52-2.56). Although a significant interaction was noted between lenalidomide and IPSS in relation to AML in the cohort analysis (Figure 1), lenalidomide was not associated with AML transformation among lower risk (OR=0.44, 95% CI=0.10-1.94) or higher risk (OR=2.06, 95% CI=0.69-6.18) MDS patients after adjustment for prognostic factors in the case-control analysis. Conclusion: To our knowledge, this study represents the largest cohort investigated outside the context of clinical trials for the rate of AML transformation among MDS patients treated with lenalidomide and the first to specifically examine non-del(5q) patients. Lenalidomide treatment was not associated with an increased risk of AML transformation among this large cohort of MDS patients. Figure 1: Incidence of acute myelogenous leukemia (AML) among myelodysplastic syndrome (MDS) patients treated with or without lenalidomide (Lena) and stratified by lower risk IPSS (low risk or intermediate-1 [0,1]) versus higher risk IPSS (intermediate-2 or high risk [2,3]), Moffitt Cancer Center, 2004-2012 Figure 1:. Incidence of acute myelogenous leukemia (AML) among myelodysplastic syndrome (MDS) patients treated with or without lenalidomide (Lena) and stratified by lower risk IPSS (low risk or intermediate-1 [0,1]) versus higher risk IPSS (intermediate-2 or high risk [2,3]), Moffitt Cancer Center, 2004-2012 Disclosures Rollison: Celgene, Inc.: Research Funding. Off Label Use: Lenalidomide given as treatment for non-del(5q) MDS and/or multiple myeloma . Shain:L&M Healthcare/Onyx/Amgen: Research Funding, Speakers Bureau; Envision/Celgene: Research Funding, Speakers Bureau. Lee:Celgene, Inc.: Research Funding. Hampras:Celgene, Inc: Research Funding. Fulp:Celgene, Inc.: Research Funding. Fisher:Celgene, Inc: Research Funding. Al Ali:Celgene, Inc: Research Funding. Padron:Icyte: Speakers Bureau; Novartis: Speakers Bureau. Lancet:Celgene, Inc: Consultancy, Research Funding. Xu:Celgene, Inc.: Employment, stock options Other. Knight:Celgene, Inc: Employment, stock options Other. List:Celgene, Inc.: Consultancy. Dalton:Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene, Inc.: Research Funding. Komrokji:Celgene: Consultancy, Research Funding.

A Single Institution Retrospective Analysis of the Effect of Erythropoiesis Stimulating Agents in Patients with Multiple Myleoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5701-5701
Author(s):  
Benjamin M Parsons ◽  
Andrew J Borgert ◽  
Angela Smith ◽  
Daniel Arndorfer
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Logistic Regression ◽  
Case Control ◽  
Control Analysis ◽  
Product Labeling ◽  
Erythropoiesis Stimulating Agents ◽  
Increased Risk ◽  
Matched Case ◽  
Case Control Analysis

Abstract Background: Erythropoiesis Stimulating Agents (ESAs) are FDA approved for chemotherapy induced anemia and anemia of chronic kidney disease. These indications are more frequent in patients with multiple myeloma. Use of ESAs has been associated with an increased risk of heart attack, stroke, venous thromboembolism (VTE), and all-cause mortality. In patients with cancer, ESA's have been associated with worse progression free survival (PFS) and overall survival (OS) Previous research regarding ESA use in patients with multiple myeloma has been limited and conflicting. In this study, we evaluate the effects of ESA use in patients with multiple myeloma. Additionally, we examined the frequency of ESA usage after the 2007 FDA safety update revising product labeling for ESAs. Methods: A retrospective chart review was conducted on patients diagnosed with active multiple myeloma between January 1st, 2000 and December 31st, 2015 at Gundersen Health System in La Crosse Wisconsin. Collected data include patient demographics, medications, lab tests, comorbidities, and the dates of any VTE, stroke, or myocardial infarction. Both a logistic regression and a matched case-control analysis were used to compare rates of complications in patients using ESAs to those that did not. ESA effect on median survival time was also calculated for each International Staging System (ISS) stage of disease. Results:There were 278 patients included for demographic analysis (Table 1), of which 268 were included in the logistic regression analysis and 124 (62 pairs) in the matched case-control analysis. A logistic regression model constructed via stepwise selection found that bone lesions at diagnosis (Odds Ratio (OR): 2.5 [1.2-5.1]), antiplatelet drug use (OR: 3.7 [1.2-11.3]) and ESA use (OR: 4.7 [2.2-9.9]) were associated with increased risk of VTE in our patient population. Use of an Angiotensin Converting Enzyme (ACE) inhibitor (OR: 0.4 [0.2-0.9]) was associated with a decreased risk of VTE. Increased odds of VTE with ESA usage (OR: 5.9 [1.9 - 18.8]) were also noted in the matched case-control analysis. There was no association found between rate of stroke and ESA usage in either logistic or matched case-control analysis. No significant association between ESA use and overall survival was noted in either logistic or matched case-control analysis. When comparing outcomes based upon pre and post FDA revised product labeling, we found a 50% reduction in ESA usage within our institution. In this same time period, the percentage of patients with multiple myeloma developing VTEs has been significantly reduced (18.6% vs 12.8% [p<0.007]). Conclusions: In our population, the use of ESAs in multiple myeloma patients was associated with increased risk of VTE. No significant association between ESA use and overall survival was noted. The observed decrease in both ESA use and rate of VTE in patients with myeloma after the 2007 revised safety labelling by the FDA may reflect practice changes in response to this revision at our institution. Further study in a prospective large multicenter dataset with further control of confounding variables is warranted. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association between malignancies and Marfan syndrome: a population-based, nested case–control study in Taiwan

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017243 ◽  
Author(s):  
Chin-Wang Hsu ◽  
Jen-Chun Wang ◽  
Wen-I Liao ◽  
Wu-Chien Chien ◽  
Chi-Hsiang Chung ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Transforming Growth Factor ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Signalling Pathway ◽  
Claim Database ◽  
Control Analysis ◽  
Research Database ◽  
Increased Risk ◽  
Nested Case Control

ObjectiveMarfan syndrome (MFS) involves a deficiency of the structural extracellular matrix component fibrillin-1 and overactivation of the transforming growth factor-β (TGF-β) signalling pathway. The TGF-β signalling pathway also actively participates in malignant transformation. Although anecdotal case reports have suggested associations between MFS/MFS-like conditions and several haematological and solid malignancies, such associations have not been thoroughly evaluated in large-scale studies. We sought to use a nationwide healthcare insurance claim database to evaluate whether patients with MFS are at increased risk of malignancy.Patients and methodsWe conducted a nested case–control analysis using a database extracted from Taiwan’s National Health Insurance Research Database. All medical conditions for each case and control were categorised using the International Classification of Diseases, 9th Revision classifications. ORs and 95% CIs for associations between MFS and malignancies were estimated using conditional logistic regression and adjusted for comorbidities.ResultsOur analyses included 1 153 137 cancer cases and 1 153 137 propensity score-matched controls. Relative to other subjects, patients with MFS had a significantly higher risk of having a malignancy (adjusted OR 3.991) and hypertension (adjusted OR 1.964) and were significantly more likely to be men. Malignancies originating from the head and neck and the urinary tract were significantly more frequent among patients with MFS than among subjects without MFS.ConclusionPatients with MFS are at increased risk of developing various malignancies. Healthcare professionals should be aware of this risk when treating such patients, and increased cancer surveillance may be necessary for these patients.

scholarly journals The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case–control study

2011 ◽  
Vol 70 (6) ◽  
pp. 956-960 ◽  
Author(s):  
W G Dixon ◽  
A Kezouh ◽  
S Bernatsky ◽  
S Suissa
Keyword(s):  
Rheumatoid Arthritis ◽  
Absolute Risk ◽  
Case Control ◽  
Glucocorticoid Therapy ◽  
Control Analysis ◽  
Increased Risk ◽  
Serious Infections ◽  
Community Physician ◽  
Case Control Analysis ◽  
Nested Case Control

BackgroundGlucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied.MethodsA cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case–control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity.ResultsFor 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04).ConclusionGlucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year.

scholarly journals No Increased Risk of Cataract in Immune Thrombocytopenia Adult Patients Treated with Eltrombopag. a French Nationwide Nested Case-Control Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2363-2363
Author(s):  
Margaux Lafaurie ◽  
Bérangère Baricault ◽  
Vincent Soler ◽  
Myriam Cassagne ◽  
Laurent Sailler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Research Funding ◽  
Case Control Study ◽  
Case Control ◽  
Adult Patients ◽  
Cumulative Exposure ◽  
Increased Risk ◽  
Nested Case Control ◽  
Control Study

Background: In preclinical studies, eltrombopag has been associated to an increased incidence of cataract in mice and rats. No increased risk has been observed in randomized controlled trials in immune thrombocytopenia (ITP) patients. During the eltrombopag extension study EXTEND, 28/302 patients developed or worsened cataract, i.e. 9.3% of the patients over a median duration of exposure of 2.4 years. Of note, 79% of these 28 patients had at least another risk factor of cataract. Real-life studies assessing the risk of cataract in ITP adult patients exposed to eltrombopag are lacking. Aim: To assess the risk of cataract with eltrombopag in a nationwide cohort of primary ITP adults. Methods: The population was the cohort of all incident primary ITP adult patients (≥18 years) in France from June 2010 (date of eltrombopag marketing in France) to June 2017. This cohort was identified within the national health insurance database using a validated algorithm combining drug exposures and international classification of diseases, version 10 (ICD-10) diagnosis codes (FAITH cohort; NCT03429660). A nested case-control study was conducted within the cohort. Cases were patients who had a surgery for cataract after ITP onset, identified using appropriate codes. Up to five controls for each case were matched on age and sex. Index date was the date of cataract surgery for cases, and the date of cataract surgery of the corresponding case for controls. Two analyses were conducted: one considering the exposure to eltrombopag as ever vs. never exposed; another considering the cumulative exposure to eltrombopag, categorized by never exposed, a 1-365 Defined Daily Dose (DDD) exposure, and a ≥365 DDD exposure. Covariables were the presence of diabetes mellitus, cumulative exposure to corticosteroids considered in prednisone equivalence dosage (by quartiles), and the presence of ophthalmological risk factors of cataract (including previous ophthalmological surgery, glaucoma and other anterior chamber risk factors). Conditional logistic regression models were used to compute adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Results: The cohort included 8,502 incident primary ITP adults. During the follow-up (31,590 patient-years in total; mean follow-up: 44.4 months), 1,097 patients were exposed to eltrombopag, including 310 with a cumulative exposure ≥365 DDDs. Overall, 573 patients had a surgery of cataract; incidence: 1.90/100 person-years (95% CI: 1.75-2.06). Fifty-seven cases occurred in patients ever exposed to eltrombopag; incidence: 1.50/100 person-years (95%CI: 1.15-1.94) in this subgroup. The nested case-control study included the 573 cases and 2699 controls. Median age was 75 years and 50% were women; the median duration of disease was 24.8 months in cases and 24.2 months in controls; 57 (9.9%) cases and 314 (11.6%) controls were exposed to eltrombopag before the index date; 14 (2.4%) and 68 (2.5%) patients had cumulative exposure to eltrombopag ≥365 DDDs, respectively. Cases were more frequently exposed to corticosteroids (83.4% vs. 75.7%), with a higher cumulative exposure to corticosteroids (median: 2800 vs. 2188 mg prednisone equivalent). Diabetes mellitus was present in 25.7% of cases vs. 25.1% of controls while ophthalmological risk factors were present in 5.4% and 2.8%, respectively. In the ever/never exposed analysis, the aOR for eltrombopag was 0.79 (95% CI: 0.58-1.07). In the cumulative exposure analysis, the aOR was 0.76 (95% CI: 0.54-1.08) in the 1-365 DDD group as compared with the never exposed group, and 0.88 (95% CI: 0.49-1.59) in the ≥365 DDD group as compared with the never exposed group. Conclusions: This nationwide pharmacoepidemiological study did not identify an increased risk of cataract in primary ITP adult patients exposed to eltrombopag. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

STK15 F31I polymorphisms and uterine cancer risk: A case-control analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5511-5511
Author(s):  
M. R. Milam ◽  
J. Gu ◽  
H. Yang ◽  
J. Celestino ◽  
W. Wu ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Smoking Status ◽  
Uterine Cancer ◽  
Case Control ◽  
Control Population ◽  
Cancer Center ◽  
Control Analysis ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies ◽  
Increased Risk

5511 Background: STK15 is a serine threonine kinase which assists chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. STK15 polymorphisms have been associated with an increased risk for breast cancer in several case-control studies. We hypothesized that STK15 polymorphisms might modulate risk of uterine cancer. Methods: Uterine cancer patients treated at M. D. Anderson Cancer Center were identified from the tumor bank database from January 1, 2000 to June 30, 2006. Two common STK15 single nucleotide polymorphisms (SNPs), F31I (T/A) and V57I (G/A), were genotyped in patients with uterine cancer and in a control population matched for age, race, and smoking status. Odds ratios (OR) and 95% confidence intervals (CI) were obtained using unconditional logistic regression analysis. Results: A total of 193 women with uterine cancer and 218 controls were genotyped for both SNPs. After adjustment for age, race, and smoking status for the F31I SNP, the homozygous variant genotype (AA) was associated with a significantly increased uterine cancer risk (OR 10.2; 95% CI 2.23–46.5). Individuals with the heterozygous genotype (TA) and a history of tobacco use also exhibited an increased risk for uterine cancer (OR 2.63; 95% CI 1.20–5.76). For the V57I SNP, neither the homozygous (AA) nor the heterozygous (GA) variant genotypes were associated with significantly altered risk for uterine cancer (OR 0.76; 95% CI 0.18–3.25 and OR 0.88; 95% CI 0.52–1.49). Conclusions: Our study demonstrates that STK15 F31I SNP is associated with an increased risk for uterine cancer. Confirmation of this pilot study is needed in a larger case-control population to evaluate this genetic variant with other known risk factors for uterine cancer. No significant financial relationships to disclose.

scholarly journals Irritable bowel syndrome and Parkinson’s disease risk: register-based studies

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Bojing Liu ◽  
Arvid Sjölander ◽  
Nancy L. Pedersen ◽  
Jonas F. Ludvigsson ◽  
Honglei Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Irritable Bowel Syndrome ◽  
Case Control Study ◽  
Case Control ◽  
Twin Registry ◽  
Increased Risk ◽  
Irritable Bowel ◽  
Nested Case Control ◽  
Control Study ◽  
Swedish Twin Registry

AbstractTo examine whether irritable bowel syndrome (IBS) was related to the future risk of Parkinson’s disease (PD), we conducted a nested case-control study in the Swedish total population including 56,564 PD cases identified from the Swedish Patient Register and 30 controls per case individually matched by sex and year of birth. Odds ratios (ORs) with 95% confidence intervals (CIs) for having a prior diagnosis of IBS were estimated using conditional logistic regression. We furthermore conducted a cohort study using the Swedish Twin Registry following 3046 IBS patients identified by self-reported abdominal symptoms and 41,179 non-IBS individuals. Through Cox proportional hazard models, we estimated hazard ratios (HRs) and 95% CIs for PD risk. In the nested case-control study, 253 (0.4%) PD cases and 5204 (0.3%) controls had a previous IBS diagnosis. IBS diagnosis was associated with a 44% higher risk of PD (OR = 1.44, 95% CI 1.27–1.63). Temporal relationship analyses showed 53% and 38% increased risk of PD more than 5 and 10 years after IBS diagnosis, respectively. In the cohort analysis based on the Swedish Twin Registry, there was no statistically significantly increased risk of PD related to IBS (HR = 1.25, 95% CI = 0.87–1.81). Our results suggest a higher risk of PD diagnosis after IBS. These results provide additional evidence supporting the importance of the gut–brain axis in PD.

scholarly journals Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case–control study

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041543
Author(s):  
Keiko Ikuta ◽  
Shunsaku Nakagawa ◽  
Kenji Momo ◽  
Atsushi Yonezawa ◽  
Kotaro Itohara ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Case Control Study ◽  
Kidney Injury ◽  
Case Control ◽  
Renal Diseases ◽  
Increased Risk ◽  
Nested Case Control ◽  
Control Study

ObjectivesThis study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI).DesignA nested case–control study.SettingA health insurance claims database constructed by the Japan Medical Data Center.ParticipantsPatients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women.InterventionsCurrent use of PPIs, NSAIDs, or antibiotics.Primary outcome measuresAcute kidney injury.ResultsDuring a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study.ConclusionsConcomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

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