Evaluation of the occurrence and management of PARP inhibitor toxicities.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18073-e18073
Author(s):  
Rachel Hatch ◽  
Sweta Patel ◽  
Christine Cambareri ◽  
Tanya Uritsky ◽  
Lainie P. Martin
Keyword(s):  
Adverse Events ◽  
Observational Study ◽  
Health System ◽  
Dose Reduction ◽  
Median Time ◽  
Management Strategies ◽  
Elevated Serum ◽  
Pharmacologic Therapy ◽  
One Year

e18073 Background: Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a major cornerstone of therapy in the management of patients with ovarian cancer and other cancer types. The most common adverse events with PARPi therapy include bone marrow suppression, gastrointestinal (GI) toxicity, and fatigue. Currently, information is scarce regarding the management of some of these adverse events. Methods: A retrospective, descriptive observational study of adult patients with gynecologic malignancy, who received at least 2 weeks of PARPi therapy, was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019, from initiation of therapy through one-year post-initiation or last follow-up. The primary endpoint was the status of PARPi therapy at the end of the study period. Secondary endpoints included time to toxicity, progression free survival (PFS), and overall survival (OS). Descriptive statistics were used to analyze all endpoints. Results: Of the 85 patients included in the study, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on PARPi therapy, 16 (19%) discontinued the due toxicity, and 40 (47%) discontinued due to progression. Of 147 unique toxicities, 67 (46%) were GI-related, 48 (33%) were hematologic, and 32 (22%) were other toxicities, including fatigue, elevated serum creatinine, hypertension, and rash. Twenty-three percent of all toxicities were categorized as grade 3 or 4 per the Common Terminology Criteria for Adverse Events v5.0. The median number of management strategies required for GI toxicities was 1 (range 1-7), hematologic toxicities was 2 (1-8), and fatigue was 1.5 (1-4). Primary management strategies included pharmacologic therapy (96%) for GI toxicities; transfusion support (65%), holding PARPi therapy (67%), and dose reduction (52%) for hematologic toxicities; and dose reduction (78%) for fatigue. Hospital admission due to PARPi toxicity occurred in 12% of patients. The median time to toxicity was 29 days (1-330) and the median time to discontinuation due to toxicity was 72.5 days (9-353). Fifty-four patients (64%) had progression of disease and 18 (21%) died within one-year of initiation. Median PFS was 181 days and median OS was 338 days, censored for time to last follow-up. Conclusions: This observational study outlines the incidence of PARPi toxicity and some of the management strategies within an academic health system, further guiding practitioners in an area with limited information.

Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system

2021 ◽  
pp. 107815522110247
Author(s):  
Rachel V Hatch ◽  
Sweta U Patel ◽  
Christine Cambareri ◽  
Tanya Uritsky ◽  
Lainie P Martin
Keyword(s):  
Observational Study ◽  
Health System ◽  
Dose Reduction ◽  
Parp Inhibitor ◽  
Management Strategies ◽  
Progression Free Survival ◽  
Adenosine Diphosphate ◽  
University Of Pennsylvania ◽  
The Status ◽  
Health System Data

Introduction Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a cornerstone of therapy in the management ovarian cancer and other cancers. PARPi are associated with significant toxicities and management strategies are primarily founded on clinical trial experience. This study aimed to provide an evaluation of patients receiving PARPi therapy within an academic health-system. Methods A retrospective, observational study of adult patients with gynecologic malignancy was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019. The primary endpoint was the status of PARPi therapy at the end of the study period. Key secondary endpoints included toxicity management strategies, time to discontinuation due to toxicity, progression free survival (PFS), and overall survival (OS). Results Of the 85 patients included, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on therapy, 15 (18%) discontinued due to toxicity, and 41 (48%) discontinued due to progression. Fifty-one percent of patients required a dose reduction due to toxicities. The median time to discontinuation due to toxicity was 69 days (9-353). Median PFS was 181 days (9-365) and median OS was 338 days (9-365). Conclusion PARPi therapy is associated with numerous toxicities that are best managed through a multi-modal approach. Importantly, about half the patients in the current study required a dose reduction. Overall, this observational study outlines the incidence of PARPi toxicities and reviews potential management strategies, further guiding practitioners in an area with limited real-world experience.

scholarly journals O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Assessment ◽  
Prevalence Rates ◽  
Clinical Predictors ◽  
Research Support ◽  
Related Data ◽  
Increased Risk ◽  
One Year

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

scholarly journals Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shilpa Tyagi ◽  
Gerald Choon-Huat Koh ◽  
Nan Luo ◽  
Kelvin Bryan Tan ◽  
Helen Hoenig ◽  
...  
Keyword(s):  
Observational Study ◽  
Management Strategies ◽  
Stroke Survivor ◽  
Stroke Survivors ◽  
Post Stroke ◽  
Memory Problems ◽  
Healthcare Needs ◽  
Stroke Study

Abstract Background Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. Method Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0–3 months (early) and 4–12 months (late) post-stroke. Results For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. Conclusion We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.

scholarly journals SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Musculoskeletal Symptoms ◽  
Day Range ◽  
One Year

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

scholarly journals Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation

2019 ◽  
Vol 91 (8) ◽  
pp. 41-46
Author(s):  
O V Knyazev ◽  
T V Shkurko ◽  
A V Kagramanova ◽  
A A Lishchinskaya ◽  
M Yu Zvyaglova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Real Life ◽  
Fecal Calprotectin ◽  
Biologic Drugs ◽  
Real Life Data ◽  
Bowel Diseases ◽  
Significant Clinical Improvement ◽  
One Year

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. Aim. To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. Materials and methods. Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. Results and discussion. Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. Conclusion. IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

P1425EFFICACY AND SAFETY OF INTRAVENOUS PARICALCITOL TREATMENT IN CHINESE HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM: A REAL-WORLD DATABASE ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Niansong Wang ◽  
Gengru Jiang
Keyword(s):  
Parathyroid Hormone ◽  
Observational Study ◽  
Secondary Hyperparathyroidism ◽  
Median Time ◽  
Real World ◽  
Hemodialysis Patients ◽  
Target Range ◽  
Total Serum ◽  
Weekly Dose

Abstract Background and Aims The aim of this retrospective, real-world data based observational study was to evaluate the efficacy, safety profile of paricalcitol in Chinese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) under routine clinical practice. Method From the Zemplar Engagement Program (ZEP) database, a total of 668 Chinese hemodialysis patients from 104 dialysis centers between January 2015 and May 2019 were included in the analysis set. Intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (Zemplar®) were analyzed and discussed via retrospective analysis of the database during the treatment. The comparison between baseline and end of treatment was made to reveal the fluctuation trend of each biomarker and reflected us with clues of IV paricalcitol’s algorithm in real-world practice. Results Patients were divided into five groups according to the duration of follow-up, which includes Month 0.5-3 (Day 14–90), Month 3-6 (Day 91–180), Month 6-12 (Day 181–360), Month 12-24 (Day 361–720) and Month 24-48 (Day 721–1440). Median iPTH levels decreased from 1183.05 pg/ml at baseline to 676.03 pg/ml at last visit by 30.88% (p < 0.0001). 56.14% of patients had a ≥30% decrease and 29.34% of patients had a ≥50% decrease in iPTH. The proportion of patients achieving the Chinese CKD-MBD Guideline target range (<600 pg/ml) increased from 9.88% at treatment initiation to 40.12% at last observation. Serum Ca levels remained within the normal range throughout the study with only a slight but statistically significant increase in the group of Month 12-24 (P=0.0479). Serum phosphate remained stable in all follow-up groups (P>0.05). Subgroup analyses of 221 patients with hyperphosphatemia at baseline >1.78 mmol/l showed a rapid phosphate reduction from 2.00±0.20 mmol/l to 1.76±0.34mmol/l by 11.64% (P< 0.0001), within the first few weeks, along with the reduction of iPTH. Of all patients, 62.72% experienced a 30% decrease in iPTH within a median time of 16.86 weeks (95% CI, 15.57-17.86), 38.17% experienced a 50% decrease in iPTH within a median time of 21.29 weeks (95% CI, 19.86-23.14). The average weekly dose of paricalcitol was 19.69±8.99ug/week. Total dose of paricalcitol used and baseline iPTH were negatively correlated with the decrease in iPTH. Conclusion This is the first national retrospective real-world observational study since IV paricalcitol is available in China since 2014. It proves that up to 20ug weekly IV paricalcitol treatment is safe and effective in China HD patients with higher iPTH level. Physicians and patients could expect significantly iPTH decrease within 16-21 weeks when IV paricalcitol is initiated. This study also encores the pre-published results of paricalcitol trials and high-quality cohorts, from the real-world perspective. In summary, IV paricalcitol is well tolerated and serves as an effective approach to treat SHPT in Chinese HD patients. Figure.1 Mean iPTH values from baseline to last measurement (pg/ml) Figure.2 iPTH changes compared with baseline stratified by baseline iPTH values (%) Figure.3 Proportion of patients with a >=30% or 50% decrease in parathyroid hormone (%) Figure.4 Changes of iPTH and P from baseline to last measurement in the subgroup of hyperphosphatemia (Mean ± SD); (Hyperphosphatemia, defined as P>1.78 mmol/l)

scholarly journals One year follow-up of patients with screen-detected metabolic syndrome in primary care: an observational study

2012 ◽  
Vol 30 (1) ◽  
pp. 40-47 ◽  
Author(s):  
C. den Engelsen ◽  
K. J. Gorter ◽  
P. L. Salome ◽  
G. E. Rutten
Keyword(s):  
Primary Care ◽  
Metabolic Syndrome ◽  
Observational Study ◽  
One Year
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