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 Effects of secondary hyperparathyroidism treatment on hemoglobin levels and erythropoietin doses in hemodialysis patients

2021 ◽  
Vol 5 (3) ◽  
pp. 088-094
Author(s):  
Massimetti Carlo ◽  
Bellasi Antonio ◽  
Feriozzi Sandro
Keyword(s):  
Observational Study ◽  
Secondary Hyperparathyroidism ◽  
Selection Criteria ◽  
Hemodialysis Patients ◽  
Single Center ◽  
Limited Sample ◽  
Limited Sample Size ◽  
The Mean ◽  
Serum Pth

Aim: Secondary hyperparathyroidism (SHPT) is an often underestimated cause of anemia in hemodialysis (HD) patients. The aim of this study was to assess the effect of pharmacological correction of SHPT on anemia and erythropoiesis-stimulating agents (ESAs) need. Methods: For the purpose of this retrospective pre-post observational study, we selected 55 HD patients, receiving HD at one single center, in the period from January 2005 to December 2020. The follow-up (F-U) lasted 12 months. The selection criteria were parathormone (PTH) levels > 300 pg/ mL, and hemoglobin (Hb) levels < 11 g/dL, despite treatment with ESAs. Parametric and non-parametric tests were used when appropriate. In the light of exploratory nature of the study, the limited sample size and in consideration of the pre-post-design, no further adjustment for potential confounders is performed. Results: The hemoglobin levels throughout the study were correlated to serum PTH (r = -.257, p < 0.01). At the end of the F-U, in the 40 patients whose PTH levels decreased ≥ 30% (responders group) Hb levels increased from 10.3 ± 0.5 g/dL to 12.2 ± 1.1 g/dL (p < 0.001), and ESAs doses decreased from 141 ± 101 IU/kg/b.w./week to 94 ± 76 IU/kg/b.w./week (p < 0.05). On the contrary, in the non-responders group Hb levels did not change 10.3 ± 0.5 gr/dL at baseline and 10.1 ± 1.1 gr/dL at F-U (P = NS), and the mean doses of ESAs increased from 144 ± 75 IU/kg/b.w./week to 218 ± 145 IU/kg/b.w./week (P = NS). Conclusion: Adequate control of SHPT is associated with concomitant improvement of anemia and decrease in ESAs need. Future endeavors are required to confirm these preliminary results.

scholarly journals Parathyroidectomy Is Associated with Reduced Mortality in Hemodialysis Patients with Secondary Hyperparathyroidism

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Tsung-Liang Ma ◽  
Peir-Haur Hung ◽  
Ing-Ching Jong ◽  
Chih-Yen Hiao ◽  
Yueh-Han Hsu ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Statistical Significance ◽  
Hemodialysis Patients ◽  
Disease Outcomes ◽  
Factors Influencing ◽  
All Cause Mortality ◽  
Marginal Statistical Significance

Secondary hyperparathyroidism increases morbidity and mortality in hemodialysis patients. The Kidney Disease Outcomes Quality Initiative Guidelines recommend parathyroidectomy for patients with chronic kidney disease and parathyroid hormone concentrations exceeding 800 pg/mL; however, this concentration represents an arbitrary cut-off value. The present study was conducted to identify factors influencing mortality in hemodialysis patients with parathyroid hormone concentrations exceeding 800 pg/mL and to evaluate the effects of parathyroidectomy on outcome for these patients. Two hundred twenty-one hemodialysis patients with parathyroid hormone concentrations > 800 pg/mL from July 2004 to June 2010 were identified. 21.1% of patients (n = 60) received parathyroidectomy and 14.9% of patients (n = 33) died during a mean follow-up of 36 months. Patients with parathyroidectomy were found to have lower all-cause mortality (adjusted hazard ratio [aHR]: 0.34). Other independent predictors included age ≥ 65 years (aHR: 2.11) and diabetes mellitus (aHR: 3.80). For cardiovascular mortality, parathyroidectomy was associated with lower mortality (HR = 0.31) but with a marginal statistical significance (p = 0.061). In multivariate analysis, diabetes was the only significant predictor (aHR: 3.14). It is concluded that, for hemodialysis patients with parathyroid hormone concentrations greater than 800 pg/mL, parathyroidectomy is associated with reduced all-cause mortality.

MO800EFFICACY AND SAFETY OF CINACALCET IN CHINESE MAINTAINANCE HEMODIALYSIS PATIENTS WITH DIFFERENT STAGES OF SECONDARY HYPERPARATHYROIDISM: RESULTS OF ACTIVE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Active Study Group
Keyword(s):  
Cohort Study ◽  
Secondary Hyperparathyroidism ◽  
Real World ◽  
Phase 1 ◽  
Fibroblast Growth Factor 23 ◽  
Public Health Problem ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Number Of Patients

Abstract Background and Aims Secondary hyperparathyroidism (SHPT), as a common complication in advanced chronic kidney disease (CKD) has become a global public health problem. Published literatures showed higher risk of bone fracture, cardiovascular events and all-cause mortality was associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce intact parathyroid hormone (iPTH) levels in patients with SHPT. However, there is no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. The ACTIVE study was designed to test the efficacy and safety of cinacalcet in treating Chinese maintenance hemodialysis patients with mild-to-severe SHPT, as well as to investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting. Method ACTIVE study was a phase IV, open-label, multicenter clinical trial including two phases: Phase 1 was a cohort study with 32 weeks’ follow-up. Phase 2 was a real-world study of 20 additional weeks in which patients who completed the cohort study decided independently whether to continue taking cinacalcet at their own cost. Eligible maintenance hemodialysis (MHD) patients with baseline iPTH ≥300 pg/mL from April 2017 to September 2019 in 23 centers in China were treated with cinacalcet orally. Patients were grouped based on their iPTH level as mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL) SHPT. Results 911 patients were screened and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The number of people who completed all 52-week follow-up in the mild, moderate and severe SHPT groups were 184 (66.91%), 164 (73.21%), and 166 (66.14%), respectively(Fig 1). The baseline and interim analysis results was published on 2020 EDTA. The number of patients achieving iPTH target (150-300 pg/mL) was 85 (31.02%) in mild group, 56 (25.00%) in moderate group and 27 (10.76%) patients in severe group at 20-week visit, and the proportion of patients achieving iPTH target was 33.94% (n=93), 24.11% (n=54) and 13.55% (n=34) at 32-week visit. The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig 2). The number of patients who reached both targets of serum calcium (Ca2+) and serum phosphorus (P) in the mild, moderate and severe SHPT group was 61 (22.26%), 42 (18.75%), 37 (14.74%) at 20-week visit, and 44 (16.06%), 34 (15.18%), 41 (16.33%) at 32-week visit, respectively. At the end of the 20th and the 32nd week of treatment, serum Ca2+×P and fibroblast growth factor-23 (FGF-23) decreased significantly compared with their baseline values (Table 1). In the extension 32-52 weeks study, the corresponding proportion of patients who achieved iPTH target in the three SHPT groups was 11.41%, 6.06%, and 4.81%, respectively. The safety analysis showed the most common treatment-related AE were hypocalcemia, hyperlipidemia and loss of appetite. This study is sponsored by Kyowa Kirin China Pharmaceutical Co., Ltd. Conclusion Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.

scholarly journals Connected health for growth hormone treatment research and clinical practice: learnings from different sources of real-world evidence (RWE)—large electronically collected datasets, surveillance studies and individual patients’ cases

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nea Boman ◽  
Luis Fernandez-Luque ◽  
Ekaterina Koledova ◽  
Marketta Kause ◽  
Risto Lapatto
Keyword(s):  
Growth Hormone ◽  
Observational Study ◽  
Case Studies ◽  
Real World ◽  
Growth Disorders ◽  
Injection Device ◽  
Growth Outcomes ◽  
Real World Evidence ◽  
High Adherence

Abstract Background A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen. Methods Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients. Here, we report on a new approach, the use of electronically recorded objective evidence of date, time, and dose taken which was obtained through a comprehensive eHealth ecosystem, based around the easypod™ electromechanical auto-injection device and web-based connect software. The benefits of this eHealth approach are also illustrated here by two case studies, selected from the Finnish cohort of the easypod™ Connect Observational Study (ECOS), a 5-year, open-label, observational study that enrolled children from 24 countries who were being treated with growth hormone (GH) via the auto-injection device. Results Analyses of data from 9314 records from the easypod™ connect database showed that, at each time point studied, a significantly greater proportion of female patients had high adherence (≥ 85%) than male patients (2849/3867 [74%] vs 3879/5447 [71%]; P < 0.001). Furthermore, more of the younger patients (< 10 years for girls, < 12 years for boys) were in the high adherence range (P < 0.001). However, recursive partitioning of data from ECOS identified subgroups with lower adherence to GH treatment ‒ children who performed the majority of injections themselves at an early age (~ 8 years) and teenagers starting treatment aged ≥ 14 years. Conclusions The data and case studies presented herein illustrate the importance of adherence to GH therapy and how good growth outcomes can be achieved by following treatment as described. They also show how the device, software, and database ecosystem can complement normal clinical follow-up by providing HCPs with reliable information about patient adherence between visits and also providing researchers with real-world evidence of adherence and growth outcomes across a large population of patients with growth disorders treated with GH via the easypod™ device.

scholarly journals The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients

2018 ◽  
Vol 21 (2) ◽  
pp. 12-22 ◽  
Author(s):  
Lilit V. Egshatyan ◽  
Natalya G. Mokrisheva
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Vitamin D Supplementation ◽  
Target Range ◽  
Receptor Agonists ◽  
Stage 4 ◽  
Calcium Phosphorus ◽  
Phosphorus Levels

Background: secondary hyperparathyroidism (SHPT) is an early complication of chronic kidney disease (CKD). Maintaining the level of 25(OH)D and parathyroid hormone concentrations in the target range reduce its associated complications (fractures and cardiovascular calcification). Aims: to examine the effectiveness of vitamin D supplementation and selective vitamin D receptor agonists treatment on SHPT in CKD. Material and methods: prospective observational study to evaluate the efficacy and safety of vitamin D therapy SHPT in 54 in patients with CKD. The first phase (24 weeks) – treatment of suboptimal 25-hydroxycalciferol (25(OH)D) levels. The second (16 weeks) – treatment colecalciferol-resistant SHPT by combination of cholecalciferol with paricalcitol. Blood samples were taken to assess parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus levels and calcium excretion. Results: After 8 weeks of cholecalciferol treatment all patients achieved 25(OH)D levels above 20 ng/ml, however 78% of patients still had SHPT. After 16 weeks, the decrease of PTH was achieved in all patients, but significantly only in patients with CKD 2 (19.2%, p< 0.01) and 3 (31%, p <0.05), compared with CKD 4 (17%, p >0.05). After 24 weeks of therapy, PTH normalized in all patients with CKD 2, in 15 (79%) with CKD 3 and in 9 (50%) patients with CKD 4. Cholecalciferol treatment resulted in a substantial increase in 25(OH)D levels with minimal or no impact on calcium, phosphorus levels and kidney function. After 24 weeks we initiated combination therapy (cholecalciferol and paricalcitol) for patients with colecalciferol-resistant SHPT (n=13). PTH levels decreased from 149.1±13.4 to 118.2±14.1 pg/ml at 8 weeks, and to 93.1±9.7 pg/ml (p <0.05) at 16 weeks of treatment. No significant differences in serum calcium, phosphorus or urinary calcium levels. Normalization of PTH was achieved in all patients with CKD 3 and in 8 patients with stage 4. One patient with CKD 4 needed an increase in paricalcitol dose. Conclusion: Cholecalciferol can be used in correcting vitamin D deficiency in patients with all stages of CKD, however, its effectiveness in reducing PTH in stage 4 is limited. Selective analogs, such as paricalcitol, were well-tolerated and effectively decreased PTH levels.

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p &lt; 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

Imatinib at Weekly Dosage May Induce and Maintain Haematologic and Molecular Remission in Chronic Eosinophilic Leukemia Harbouring FIP1L1-PDGFRA Fusion Gene- An Extended Follow-up Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1755-1755
Author(s):  
Grzegorz Helbig ◽  
Malgorzata Calbecka ◽  
Justyna Gajkowska ◽  
Andrzej Moskwa ◽  
Alina Urbanowicz ◽  
...  
Keyword(s):  
Median Time ◽  
Fusion Gene ◽  
Hypereosinophilic Syndrome ◽  
Imatinib Treatment ◽  
Weekly Dose ◽  
Rt Pcr ◽  
Molecular Remission ◽  
Chronic Eosinophilic Leukemia ◽  
Weekly Dosage

Abstract Background. A small proportion of patients with hypereosinophilic syndrome (HES) demonstrate the presence of an interstitial deletion in chromosome 4 leading to the creation of the imatinib-responsive fusion gene- FIP1L1-PDGFRA (F/P). Recently, we showed that a single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukemia (CEL) with detectable F/P transcript. Here, we present data from 12 patients CEL and HES, 11 of which were F/P positive, who achieved a rapid complete haematologic remission (CHR) with daily imatinib treatment and remission was then maintained with a weekly imatinib schedule. Design and methods. Twelve patients, 11 out of 12 with detectable F/P were treated with imatinib at the initial doses varies between 100–400mg. There were 10 male and 2 female with a median age of 57 years (19–80). Median time to start imatinib was 23 months (1–204 months). The imatinib dose was de-escalated while patients remained in haematologic remission. As a response maintenance, once weekly imatinib was established in all cases. Results. All studied patients achieved a complete haematologic remission (CHR) and 100% of cases with detectable F/P fusion gene before imatinib, demonstrated a molecular remission determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The breakpoints occured within exon 12 of PDGFRA whereas breakpoints dispersed across the FIP1L1 locus occuring between exons 10 and 13. Median time to achieve CHR was 13 days (4–90), and median time to molecular remission was 9 months (4–24). As a remission maintenance, imatinib doses were set at 100mg weekly in 9 pts and 200mg weekly in 3. With a median follow-up of 21 months (8–49 months) all pts remain in CHR. The FIP1L1-PDGFRA is undetectable in 11 patients by RT-PCR. Conclusions. Imatinib at weekly dosage may induce and maintain remission in patient with CEL expressing F/P fusion gene. This strategy appears to be safe and cost savings.

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