scholarly journals Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Piolatto ◽  
Paola Berchialla ◽  
Sarah Allegra ◽  
Silvia De Francia ◽  
Giovanni Battista Ferrero ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Renal Impairment ◽  
Observational Study ◽  
Iron Overload ◽  
Iron Loading ◽  
Comprehensive Comparison ◽  
Dispersible Tablets ◽  
One Year ◽  
Safety Features

AbstractDeferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

Vitamin C Status in Transfusionally Iron-Overloaded Patients On Long-Term Deferasirox and Its Relationship to Myocardial Iron Removal.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2005-2005
Author(s):  
Maciej W Garbowski ◽  
Margarete Fabre ◽  
Patricia Evans ◽  
John B Porter
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Research Funding ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Liver Iron ◽  
One Year ◽  
The Impact

Abstract Abstract 2005 Poster Board I-1027 Background Although the benefits to iron balance of supplementing deferoxamine therapy with ascorbic acid (AA, 2-3mg/kg/day) are well established, the role of this approach with deferasirox (DFX) chelation is unknown. We have previously reported that fasting plasma ascorbate (FPA) was significantly lower in patients on long-term DFX without AA supplementation (30.3 ± 20.8 mM) than in healthy controls (60.3 ± 12.6 mM, P<0.0001), with deficiency (defined as >2 SDs from the adult control mean) present in 72% of patients not receiving AA supplementation (Sarantos et all, Blood 112, Abstract 1858, 2008). It is therefore important to establish prospectively the relevance of ascorbate status to iron balance and also to myocardial iron loading in DFX-treated patients. Here we examine changes in FPA and markers of iron overload in the same patients over at least one year follow-up and examine the impact of AA supplementation in selected patients. Patients and Methods: 21 adult patients with a range of transfusional iron overload conditions excluding Sickle Cell Disease (17 with b-Thalassaemia Major, 2 with Congenital Syderoblastic Anaemia, 1 with Red Cell Aplasia, 1 with Diamond-Blackfan Anaemia) on long-term DFX chelation (duration of treatment 3-6 years, mean dose 27.1mg/kg/day) had measurements of FPA, ferritin, cardiac and hepatic T2* on two occasions, separated by a period of approximately one year (median 419 days). Of these, 10 received AA supplementation (2-3mg/kg/day) and 11 did not. The decision to prescribe AA was based on clinical criteria and patient preference rather than by randomisation. FPA was measured under controlled conditions: a 4 ml fasting heparinised blood sample was taken, placed immediately on ice and centrifuged at 4oC at 2000g for 10 minutes. An equal volume of 10% trichloroacetic acid (TCA) was added, the sample re-spun, and stored at —80oC until measurement of vitamin C fluorimetrically as previously described (Speek et al, 305, J Chromatogr, 1984). Results: In 10 patients who received AA supplementation for 1y (432 ± 96 (SD) days) , the FPA increased significantly from mean baseline of 35.99 ± 21.02 mM to 46.94 ± 14.69 mM at follow up (p=0.03) correcting the deficiency in 3 of the 5 scorbutic patients. FPA increased slightly but not significantly (p=0.3) in 11 patients without supplementation rising from 27.4 ± 15.8 mM to 34.0 ± 12.37 mM where deficiency was corrected in 2 of the 8 scorbutic patients. The increment in FPA levels in un-supplemented patients correlated with decrements in liver iron (LIC, r=-0.64, p=0.04), with mean liver R2* decreasing from 209.24 to 178.07 Hz (i.e. estimated LIC from 7.01 to 6.08 mg Fe/g dry weight (dw)), consistent with previous observations that iron overload accelerates oxidation of AA. Significant improvements in myocardial iron (shown as decreasing myocardial R2*) were seen in ascorbate replete patients at 1y (n=13, mean FPA 48.73 ± 10.61 mM) from a mean myocardial R2* of 61.4 to 52.5Hz p=0.008, i.e. T2* of 16.2ms to 19ms). By contrast, in patients who remained AA deficient (mean FPA 26.28 ± 8.44uM, n=8), the improvement in myocardial R2* was less marked (from 50.41 to 46.65Hz, i.e. T2* 19.8 to 21.4 ms) and did not reach significance. Conclusions: AA deficiency is a significant risk in transfusionally iron loaded patients on long term DFX without AA supplementation, particularly in patients with high levels of body iron loading. Our findings suggest that improvement in myocardial and liver iron with DFX therapy is more likely in AA replete than AA deficient patients. A prospective randomised study of the effects of AA supplementation on iron overload and myocardial iron in DFX treated patients is indicated but until such data are available, we recommend that patients on long term chelation with DFX have FPA levels assessed and consideration is given to supplementing deficient patients. Disclosures: Garbowski: Novartis: Research Funding. Evans:Novartis: Research Funding. Porter:Novartis: Consultancy, Research Funding.

One-Year Post-Transplant Serum Ferritin Level Is a Predictor of Long-Term Survival Following Allogeneic Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3453-3453 ◽  
Author(s):  
Stuart L Goldberg ◽  
Marc Elmann ◽  
Mark Kaminetzky ◽  
Eriene-Heidi Sidhom ◽  
Anthony R Mato ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Cox Regression ◽  
Allogeneic Transplantation ◽  
Term Survival ◽  
Post Transplant ◽  
Kaplan Meier ◽  
One Year

Abstract Abstract 3453 Individuals undergoing allogeneic transplantation receive multiple red blood cell transfusions both as part of the transplant procedure and as part of the pre-transplant care of the underlying disease. Therefore these patients may be at risk for complications of transfusional iron overload. Several studies have noted that individuals entering the transplant with baseline elevated serum ferritin values have decreased overall survival and higher rates of disease relapse. Whether the iron is a direct contributor to inferior outcomes or is a marker of more advanced disease (thereby requiring greater transfusions) is unclear. Little is known about the incidence and consequences of iron overload among long-term survivors of allogeneic transplantation. Methods: Using Kaplan-Meier and Cox regression analyses, we performed a single center, retrospective cohort study of consecutive allogeneic transplants performed at Hackensack University Medical Center from January 2002 through June 30, 2009 to determine the association between serum ferritin (measured approximately 1 yr post allogeneic transplant) and overall survival. Results: During the study time frame, 637 allogeneic transplants (Donor Lymphocyte Infusion procedures excluded) were performed at our center and 342 (54%) survived ≥ one year. Among 1-year survivors 240 (70%) had post-transplant serum ferritin values available for review, including 132 (55%) allogeneic sibling, 68 (28%) matched unrelated, and 40 (17%) mismatched unrelated donor transplants. The median post-transplant ferritin value among 1-year survivors of allogeneic transplant was 628 ng/ml (95% CI 17, 5010), with 93 (39%) above 1000 ng/ml and 40 (17%) above 2500 ng/ml. The median post-transplant ferritin levels varied by underlying hematologic disease (aplastic anemia = 1147, acute leukemia = 1067, MDS = 944, CLL = 297, CML = 219, lymphoma = 123, multiple myeloma = 90). The Kaplan-Meier projected 5-year survival rate was 76% for the cohort that had survived one year and had available ferritin values. Fifty late deaths have occurred; causes of late death were disease relapse (n=37, 74%), GVHD (n=7, 14%), infection (n=4, 8%), cardiac (n=1, 2%) and second malignancy (n=1, 2%). The 1-year post-transplant serum ferritin value was a significant predictor of long term survival. Using a cut-off ferritin value of 1000 ng/ml, the 5-year projected survivals were 85% (95 CI 75%-91%) and 64% (95% CI 52–73%) for the low and high ferritin cohorts respectively (Figure, log-rank p<0.001), with a hazard ratio of 3.5 (95% CI 2–6.4, p<0.001). Similarly a serum ferritin value >2500 ng/ml was associated with inferior survival (HR 2.97, p<0.001). Underlying hematologic disease also correlated with 5-year projected survival including 70%, 83%, and 89% for acute leukemia/MDS, lymphoma/myeloma/CLL, and aplastic anemia/CML groupings, respectively (log-rank p<0.01 for leukemia/MDS vs other groupings). Patients receiving bone marrow grafts did better than those receiving peripheral blood stem cells (HR = 2.2; p = 0.03). Age, gender, donor type (sibling, matched unrelated, mismatch unrelated) and intensity of regimen (ablative vs. non-myeloablative) were not predictive of inferior survival in univariate analysis. In the multivariate Cox-regression analysis, elevated post-transplant ferritin >1000 ng/ml (HR 3.3, 95%CI 1.6–6.1; p<0.001) and diagnosis of acute leukemia/MDS (HR 4.5, 95%CI 1.1–18.7; p=0.04) remained independent predictors of inferior survival, even when adjusted for age, gender, type of graft, donor type, and intensity of conditioning regimen. Relapse deaths (25% vs. 9%; p<0.001) and GVHD deaths (6% vs 0.6%; p=0.03) were more common in the high ferritin cohort. Conclusions: Among patients who have survived one-year following allogeneic transplantation, a post-transplant serum ferritin value greater than 1000 ng/ml is a predictor of inferior long-term outcomes. To our knowledge this is the first report on the importance of late monitoring of serum ferritin, but it is in agreement with prior studies suggesting a pre-transplant ferritin value is a predictor of outcomes. Prospective studies attempting to modify outcomes by reducing post-transplant iron overload states are needed. Disclosures: No relevant conflicts of interest to declare.

Patient (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5042-5042 ◽  
Author(s):  
Celestia S. Higano ◽  
Shawn H. Zimberg ◽  
Sabina Dizdarevic ◽  
Lauren Christine Harshman ◽  
John Logue ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Interim Analysis ◽  
Routine Clinical Practice ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Observation Methods ◽  
Short And Long Term ◽  
Grade 3

5042 Background: Ra-223, a targeted alpha therapy, prolonged survival with good safety in metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial. REASSURE will evaluate Ra-223 short- and long-term safety in routine clinical practice settings. This is the first planned interim analysis (median 7 mo observation). Methods: This global, prospective, single-arm, observational study enrolled pts with mCRPC with bone metastases (mets) for whom Ra-223 therapy was planned. Follow-up will continue up to 7 years after last Ra-223 dose. Results: 1106 pts (437 N. America, 665 Europe, 4 not recorded) enrolled from 2 Sep 2014 to 22 Sep 2016. Baseline data are available from 583 pts receiving 1st- (1L), 2nd- (2L), or ≥3rd-line (≥3L) Ra-223 for mCRPC(Table). The majority of pts (n=369, 63%) completed 5–6 doses (1L, 70%; 2L, 64%; ≥3L, 49%); median 6 doses (1L,6; 2L, 6; ≥3L, 4). Treatment-emergent drug-related AEs occurred in 215 pts (37%). Post-treatment grade 3/4 thrombocytopenia occurred in 14 pts (2.4%) and anemia in 45 (7.7%). Conclusions: In routine clinical practice, Ra-223 was associated with no short-term safety concerns and appeared to be used in pts with less advanced mCRPC than in ALSYMPCA. The majority of pts on 1L/2L Ra-223 therapy received 5–6 doses. Ra-223 was often used with abiraterone or enzalutamide, but not chemotherapy. The next interim analysis in 2019 will report long-term safety and outcomes on all pts. Clinical trial information: NCT02141438. [Table: see text]

Clinical outcomes and patient (pt) profiles in REASSURE: An observational study of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 32-32
Author(s):  
Celestia S. Higano ◽  
Fred Saad ◽  
A. Oliver Sartor ◽  
Kurt Miller ◽  
Peter Conti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Practice ◽  
Observational Study ◽  
Clinical Outcomes ◽  
Bone Fractures ◽  
Bone Marrow Suppression ◽  
Routine Clinical Practice ◽  
Metastatic Sites

32 Background: Ra-223 is a targeted alpha therapy that showed a survival advantage and favorable safety profile in the phase 3 ALSYMPCA trial in pts with mCRPC. REASSURE (NCT02141438) is evaluating the long-term safety of Ra-223 in routine clinical practice in pts with mCRPC over a 7-year follow-up period. Methods: In this global, prospective, single-arm, observational study, the second prespecified interim analysis (data cut-off March 2019) evaluated safety and clinical outcomes of Ra-223 in pts with mCRPC. Primary outcome measures were incidence of second primary malignancies (SPM), bone marrow suppression and short- and long-term safety in pts who had ≥1 Ra-223 dose. Secondary outcomes included overall survival (OS). Results: For 1465 pts in the safety analysis, median follow up was 11.5 months. Median PSA (n=1053), ALP (n=1048), and LDH (n=555) levels at baseline were 59 ng/mL, 135 U/L, and 269 U/L, respectively. 81% of pts had bone metastases only at baseline; 19% of pts had other metastatic sites, mostly in the lymph nodes. 19% of pts had <6 metastatic sites, 47% had 6–20 sites, 20% had >20 lesions but not a superscan, and 6% had a superscan. 45%, 38%, 37%, 9%, and 8% of pts received prior abiraterone, docetaxel, enzalutamide, cabazitaxel, or sipuleucel-T as prior therapies, respectively. Median number of Ra-223 doses received was 6; 67% of pts had ≥5 doses. SPM occurred in 1% of pts. The most common treatment-emergent drug-related adverse event (AE) of any grade was diarrhea (11%). 10% of pts had a bone-associated event, 5% had fractures, and 15% had a hematological AE. Median OS was 15.6 months (95% CI 14.6–16.5). Conclusions: In REASSURE, there was a low incidence of SPM, bone fractures, and bone marrow suppression after Ra-223 treatment, with no new AEs identified. This study confirms that in routine clinical practice, Ra-223 AE rates were low, and pts generally received ≥5 doses. Clinical trial information: NCT02141438. [Table: see text]

P3849Baseline profile of patients treated for acute venous thromboembolism in routine clinical practice according to age and renal function in the RE-COVERY DVT/PE global cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Ageno ◽  
I B Casella ◽  
C K Han ◽  
S Schellong ◽  
S Schulman ◽  
...  
Keyword(s):  
Renal Function ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Observational Study ◽  
Anticoagulant Therapy ◽  
Patient Characteristics ◽  
Routine Clinical Practice ◽  
Moderate Renal Impairment ◽  
Acute Venous Thromboembolism

Abstract Background Observational studies provide the opportunity to evaluate routine practice without the selection and treatment criteria imposed in randomized clinical trials (RCTs). Purpose Using data from the RE-COVERY DVT/PE global observational study (enrolment January 2016 to May 2017), we describe the baseline profile of patients treated for acute venous thromboembolism (VTE) in routine clinical practice according to age and renal function. Methods Baseline patient characteristics, clinical features (comorbidities/medical history), and anticoagulant therapy were tabulated descriptively for the subgroups of age (<75, ≥75 years) and creatinine clearance (<30, 30 to <50 [moderate impairment], 50 to <80 [mild impairment], ≥80 mL/min). Anticoagulant therapy at baseline and at hospital discharge or 14 days after diagnosis (whichever was later) was recorded. Results In this observational study of 6122 patients with acute deep vein thrombosis, the proportions of patients at baseline who were ≥75 years of age (25.2%) or who had mild to moderate renal impairment (38.1%) were higher than in RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) for acute VTE treatment (∼12–13% elderly and ∼26–29% with mild or moderate renal impairment) (from analyses of the RE-COVER trials; Hokusai-VTE and AMPLIFY). Older patients and those with renal impairment were more often female and were more likely to have comorbidities than the younger or normal renal function groups (Table). At the time of hospital discharge or 14 days after diagnosis, whichever was later, the majority was treated with NOACs (54%). Vitamin K antagonists were prescribed to approximately 1 in 5 patients. The use of NOACs decreased with worsening renal function, whereas the proportions treated with parenteral anticoagulation alone increased in the moderate renal impairment group compared with patients with normal renal function. Conclusion The population treated for acute VTE in routine clinical practice includes more elderly and renally impaired patients than represented in RCTs. These baseline data provide a snapshot of patient characteristics and patterns of anticoagulant therapy. Acknowledgement/Funding Funded by Boehringer Ingelheim

976-P: Evaluation of Hybrid Closed-Loop Insulin Delivery System for Patients with Type 1 Diabetes in Real-World Clinical Practice: A One-Year Qualitative Observational Study

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 976-P
Author(s):  
AHMED H. ELDIB ◽  
SHAHEEN TOMAH ◽  
SHILTON E. DHAVER ◽  
HANNAH GARDNER ◽  
MHD WAEL TASABEHJI ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Practice ◽  
Observational Study ◽  
Delivery System ◽  
Real World ◽  
Closed Loop ◽  
Insulin Delivery ◽  
Insulin Delivery System ◽  
One Year

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1421-1421 ◽  
Author(s):  
Robert I. Liem ◽  
Cynthia Rigsby ◽  
Richard J. Labotka ◽  
Andrew DeFreitas ◽  
Alexis A. Thompson
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if &lt; 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=&lt;0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range &gt; 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Costs, Persistence, and Hospitalizations Associated with the Use of Iron-Chelating Therapies in Sickle Cell Disease in Medicaid Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3152-3152 ◽  
Author(s):  
Edward P Armstrong ◽  
Grant H Skrepnek ◽  
Samir K. Ballas ◽  
Peter Kwok ◽  
Susan Snodgrass ◽  
...  
Keyword(s):  
Iron Overload ◽  
Resource Use ◽  
Healthcare Costs ◽  
Research Funding ◽  
Cox Regression ◽  
Treatment Discontinuation ◽  
Cell Disease ◽  
Pharmaceutical Corporation ◽  
One Year

Abstract Abstract 3152 Objective: Patients with Sickle Cell Disease (SCD) receiving chronic blood transfusions require iron chelation therapies (ICTs) and good adherence to ICT to avoid sequellae of iron overload. This study evaluated cost, persistence, and medication adherence to ICTs based on a nationwide sample of Medicaid recipients with SCD. Methods: This retrospective cohort study evaluated healthcare claims from 2006 to 2010 captured within the Thomson Reuters 10 states Medicaid MarketScan database. Patients with ≥ 1 SCD diagnosis code (282.6x), ≥ 2 claims for ICT medications (deferoxamine (DFO), deferosirox (DFX)), continuously enrolled for ≥ 6 months prior to ICT initiation through 365 days post initiation of ICT were included. ICT utilization was obtained using NDC codes and HCPCS codes. Patients were classified into 3 groups based on their ICT use: DFO only, DFX only, and switches from DFO to DFX. Outcomes evaluated included adherence and persistence to ICT, frequency of SCD crises related hospitalizations, and overall costs. ICT adherence was evaluated using medication possession ratio (MPR) and persistence was defined as medication refill gap of ≥ 6 weeks. Multivariate linear, logistic, and Cox regression analyses were performed after controlling for demographics, number of transfusions, capitated Medicaid coverage, pre-index cost (6months prior to ICT initiation), number of hospitalizations, adherence, and risk-adjusted case-mix comorbidity. Results: A total of 484 SCD patients receiving ICTs from 2006 to 2010 within the 10 states were identified. The average age was 18.9 ±11.2 years of age, 45% (n =218) were male, and 64.7% (n=313) were African American. A total of 25.4% (n =123) patients, switched from DFO to DFX while 1.7% (n = 8) switched from DFX to DFO during one-year post-ICT initiation. Patients receiving DFX only, DFO only, or both ICTs received an average of 2.68 (±3.2), 3.54 (±3.0), 3.59 (±3.2) transfusions during the study period, respectively. Compared to pre-ICT period, the number of transfusion claims increased in all three cohorts during the study period; the mean difference was 2.7 in DFO, 3.3 in DFX, and 4.1 in the both ICT group. The Cox regression assessing long-term medication persistency indicated a 1.37 times higher likelihood of treatment discontinuation with DFO compared to DFX. Overall MPR was low in both groups; following one year of treatment, 37.4% remained on DFX compared to 15.7% on DFO (Figure 1). No differences were observed in total healthcare costs, number of hospitalizations and associated costs for SCD-related crises between the DFX only and DFO only cohorts. Meaningful differences in treatment discontinuation between the two treatment groups did not occur until 220+ days during the study period (Figure 1). Thus, a one year timeframe may be inadequate to observe complete impact of ICT adherence on sequellae of iron overload and subsequent resource use. Lengthening the study period beyond one year may be necessary to fully capture the long term impact of adherence on outcomes related to iron overload. Conclusion: This study indicated that there were more switches from DFO to DFX, higher medication persistency rate with DFX than DFO, and similar total healthcare costs, numbers of SCD crisis-related hospitalizations, and SCD crisis-related costs between DFO & DFX cohorts. Treatment discontinuation was generally high for all groups, especially for those on DFO, with a one year discontinuation rate of approximately 85%. Future research using a longer observation period than one year will be necessary to assess effects on long term clinical outcomes, resource use, and healthcare costs between different ICTs. Kaplan-Meier Graph for Treatment Discontinuation Between Deferoxamine and Deferasirox Disclosures: Armstrong: Novartis Pharmaceutical Corporation: Consultancy, Research Funding. Skrepnek:Novartis Pharmaceutical Corporation: Consultancy, Research Funding. Ballas:Novartis Pharmaceutical Corporation: Consultancy. Kwok:Novartis Pharmaceutical Corporation: Employment. Snodgrass:Novartis Pharmceutical Corporation: Employment. Sasane:Novartis Pharmaceutical Corporation: Employment.

scholarly journals Iron overload in transfusion-dependent patients

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 337-344 ◽  
Author(s):  
Thomas D. Coates
Keyword(s):  
Iron Overload ◽  
Iron Homeostasis ◽  
Prolonged Exposure ◽  
Iron Chelation ◽  
Close Relation ◽  
Therapeutic Strategies ◽  
Clinical Approach ◽  
Iron Loading ◽  
Marrow Activity

Abstract Before the advent of effective iron chelation, death from iron-induced cardiomyopathy occurred in the second decade in patients with transfusion-dependent chronic anemias. The advances in our understanding of iron metabolism; the ability to monitor iron loading in the liver, heart, pancreas and pituitary; and the availability of several effective iron chelators have dramatically improved survival and reduced morbidity from transfusion-related iron overload. Nevertheless, significantly increased survival brings about new complications such as malignant transformation resulting from prolonged exposure to iron, which need to be considered when developing long-term therapeutic strategies. This review discusses the current biology of iron homeostasis and its close relation to marrow activity in patients with transfusion-dependent anemias, and how biology informs clinical approach to treatment.

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