A Randomized Phase II Study Evaluating the Efficacy and Safety of Deferasirox Versus Deferoxamine in Patients with Sickle Cell Disease (SCD): 2-Year Results Including Pharmacokinetics (PK) and Safety of Deferasirox with Concomitant Hydroxyurea Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1082-1082 ◽  
Author(s):  
Elliott Vichinsky ◽  
Marcela Torres ◽  
Jonathan Glass ◽  
Caterina P Minniti ◽  
Stéphane Barrette ◽  
...  
Keyword(s):  
Liver Function ◽  
Serum Creatinine ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Post Dose ◽  
Safety And Efficacy ◽  
History Of

Abstract Abstract 1082 Background: Long-term efficacy and safety of the iron chelator deferasirox in SCD patients has been previously reported (Vichinsky et al. BJH 2011). Hydroxyurea (HU), a common treatment for SCD, is associated with adverse events (AEs) such as bone marrow depression. However, long-term data for iron chelation and concomitant HU are limited. This study provides further efficacy and safety data for deferasirox including PK and safety data + HU. Methods: SCD patients aged ≥2 yrs and iron overload from blood transfusions were enrolled and randomized 2:1 to deferasirox (DFX; 20 mg/kg/day) or deferoxamine (DFO; 175 mg/kg/week [wk]) for 24 wks (24-wk DFX or DFO cohort). DFO patients then crossed over to DFX; all patients received DFX up to Wk 52. Patients entered a 52-wk extension receiving DFX (DFX up to 2 yrs cohort). PK sampling was carried out pre- and 2 hrs post-dose in patients on DFX at Wk 12. Plasma concentrations of DFX and iron-complex Fe-[DFX]2 were determined using a validated LC-MS/MS method. Dose adjustments were implemented for changes in patient weight, serum ferritin, serum creatinine, liver function tests and rash. Primary objective was DFX safety compared with DFO during 24 wks. Secondary objectives included DFX safety and efficacy for up to 2 yrs and DFX safety in patients with concomitant HU. Results: 24-weeks, DFX (n=135) vs DFO (n=68). Patients were severely iron overloaded at baseline (BL); 37% had serum ferritin ≥4000 ng/mL (median 3385 ng/mL). In the DFX and DFO cohorts, respectively, 93 and 78% of patients completed 24 wks of treatment. AEs leading to discontinuation were reported by 0 and 1 (1.8%) patient in the DFX and DFO cohorts, respectively. Investigator-assessed drug-related AEs were reported in 27 and 29% of patients in the DFX vs DFO cohort, respectively; most common (>5%) were gastrointestinal (DFX vs DFO cohort: diarrhea 10.4 vs 3.6%; nausea 5.2 vs 3.6%). Serious AEs (any causality) were reported in 30 and 36% of patients in the DFX vs DFO cohort, respectively. One death occurred in the DFX cohort, not considered drug-related (patient had past history of multi-organ failure). At the 3–6 month timepoint, median change from BL in serum ferritin was –196 (range –4029 to 10,168) and –400 (range –10,001 to 3908) ng/mL for DFX (n=130) and DFO (n=58) cohorts, respectively. Up to 2 years DFX (n=188). 135 (72%) patients who received DFX completed the study; 5 (3%) patients discontinued due to AEs. Average actual dose was 21.2 ± 3.6 mg/kg/day. Most common investigator-assessed drug-related AEs (>5%) were diarrhea (11.7%), nausea (6.9%) and abdominal pain (5.3%). Drug-related serious AEs were reported in 8 (4.3%) patients; most common were increased aspartate aminotransferase (AST) and abnormal liver function test (n=2, for each). One additional death occurred; not considered drug-related (patient had history of congestive heart failure with worsening pulmonary hypertension). 4 patients had 2 consecutive serum creatinine increases >33% above BL and >upper limit of normal; increases were transient and resolved with dose adjustment or temporary interruption. Mean ± SE change from BL in serum ferritin (per-protocol, adjusted for amount of transfused blood) was –683 ± 205 ng/mL (n=87). PK, safety and efficacy of DFX + HU (n=28) and DFX (n=160). Mean DFX concentration (μmol/L) pre- and 2-hr post-dose were similar in patients receiving DFX + HU (n=14) vs DFX (n=81); pre-dose 13.3 vs 19.8, post-dose 74.2 vs 79.4. Mean Fe-[DFX]2 concentration (μmol/L) pre- and post-dose was similar in patients receiving DFX + HU (n=14) vs DFX (n=85); pre-dose 0.9 vs 0.6, post-dose 1.9 vs 1.7. One of 5 patients discontinuing DFX due to AEs was receiving concomitant HU. Overall the type and incidence of AEs in patients receiving DFX + HU vs DFX were similar (Table). At the 21–24 month time-point, mean change in serum ferritin was –593 ng/mL (n=15) and –721 ng/mL (n=81) for DFX + HU vs DFX cohorts, respectively. Conclusions: Consistent with previous studies, this study confirms that deferasirox has a clinically manageable safety profile, and is comparable overall with DFO in SCD patients, with many AEs related to the underlying condition (eg, sickle cell anemia with crisis, pyrexia, infections). This study confirms the long-term efficacy of deferasirox with clinically meaningful reductions in serum ferritin over 2 years. PK, efficacy and overall safety of deferasirox were not influenced by concomitant HU. Disclosures: Vichinsky: Novartis: Honoraria, Research Funding. Habr:Novartis: Employment. Lynch:Novartis: Employment. Zhang:Novartis: Employment. Files:Novartis: Speakers Bureau; Medical University of South Carolina: Research contract agreement.

scholarly journals Long-Term Outcome of Deferasirox Chelation in Patients with Thalassemia Major

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3620-3620
Author(s):  
Sule Unal ◽  
Neslihan Kalkan ◽  
Mualla Cetin ◽  
Fatma Gumruk
Keyword(s):  
Serum Creatinine ◽  
Sample Size ◽  
Serum Ferritin ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
The Other ◽  
Single Center ◽  
Other Hand

Abstract Introduction: Iron overload is one of themajor complicationsof transfusion treatment in patient with thalassemia major. Deferasirox is a once-daily orally active iron chelator and long-term efficacy and safety data are being published. Herein we report the long-term follow-up data of thalassemia major patients in a single center. Methods: Of the 67 patients with thalassemia major who were under follow-up in a single center, 42 who were on deferasirox chelation for at least three years were included in the study. Patients' initial serum ferritin, ALT, creatinine, cardiac T2* and hepatic T2* values were recorded at the time of deferasirox initiation and at last visit. Deferasirox was not initiated as an iron chelator to none of the patients with a cardiac T2* value below 8 ms. All of the patients had creatinine clearance above 40 ml/minute and had serum creatinine levels within age appropriate normals at deferasirox initiation. None of the patients received any other chelations during the follow-up period. Results: Mean age of the patients were 16±9.4 years (2-33.4 years) at initiation of deferasirox and 22 (52%) were females. Eighteen (43%) of the patients were splenectomized. Median follow-up time of deferasirox chelation was 7.9 years (3-10). The median deferasirox doses at initiation of chelation and at last visit were 20.5 mg/kg/day and 30.7 mg/kg/day (7-40), respectively. Serum ferritin levels decreased significantly with deferasirox chelation (median 1969 ng/ml (516-5404) vs 1113 ng/ml (339-4003), p<0,001). We did not find statistically significant difference between the inital cardiac T2* values and the values at the last visit (median 25 .3 ms((8.7-42) vs 32 ms (6.6-42), p=0.607), despite a dramatic increase. On the other hand, hepatic T2* values did not significantly change compared to initial values, as well (median 3.7 ms (1-13.6) vs 3.3 (1-16), p=0.865). However of the patients who had cardiac T2* value between 10-20 ms, 67% was found to have T2* value above 20 ms by the end of the follow-up duration. On the other hand 53% of the patients with hepatic T2* value below 3.5 ms, had T2* values above 3.5 ms by the end of the follow-up, indicating improvement in iron stores. None of the patients exibited an adverse event that requires cessation of the drug totally, but patients exibited transient hypertransaminasemia that required transient cessation and/or dose decrement. The changes in serum ALT and serum creatinine levels at the initiation and at last visit were not significant. Conclusions: This is a a study that includes patients with a relatively long duration of follow-up. Although the cardiac T2* values improved by the end of the follow-up, this change was not found statistically significant. This can be attributed to the sample size and in a larger sample size, the change might be found significant. Additionally, the patients included in the study were composed of not only naive patients to chelation but also of the patients who were imcomplant to previous chelation and who were highly iron loaded before initiation of deferasirox. Disclosures No relevant conflicts of interest to declare.

MO559ASCEND-ND: STUDY DESIGN AND BASELINE CHARACTERISTICS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Vlado Perkovic ◽  
Allison Blackorby ◽  
Borut Cizman ◽  
Kevin Carroll ◽  
Alexander Cobitz ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Trial Design ◽  
Rescue Therapy ◽  
Transferrin Saturation ◽  
Statistical Testing ◽  
Efficacy And Safety ◽  
Primary Endpoints ◽  
History Of ◽  
Baseline Characteristics

Abstract Background and Aims The Anemia Study in Chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Non-Dialysis (ASCEND-ND; NCT02876835) trial is evaluating the efficacy and safety of daprodustat when compared with darbepoetin alfa in CKD patients with anaemia not requiring dialysis. We report the trial design as well as key baseline characteristics of participants. Method Eligible patients from 39 countries were adults with CKD stages 3–5 who were able to provide informed consent and demonstrated adherence to daprodustat placebo tablets and study procedures during the run-in period. Patients were eligible if (1) they were not using erythropoiesis stimulating agents (ESAs) and had a screening haemoglobin (Hb) 8 to 10 g/dL or if (2) they were receiving ESAs with screening Hb of 8 to 12 g/dL. Patients were required to be iron replete [transferrin saturation (TSAT) &gt;20% and serum ferritin &gt;100 ng/mL] at screening. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open-label (sponsor-blind) trial design with blinded endpoint assessment. An IDMC conducts regular reviews of unblinded safety and efficacy data and makes recommendations for additions or adjustments. An external, independent and blinded Clinical Events Classification (CEC) group, led by the Duke Clinical Research Institute, in collaboration with George Clinical, adjudicate predefined events. During the study, both groups had randomised treatment adjusted using a protocol-defined algorithm targeting a Hb range of 10 to 11 g/dL. Participants also followed protocol-defined iron management criteria to ensure they remained iron replete. Additionally, an anaemia rescue algorithm was in place to minimise the risk of extended periods of inadequate Hb response and to ensure consistent application of rescue therapy across the study. The co-primary endpoints are mean change in Hb between baseline and Evaluation Period (EP; Weeks 28 to 52, inclusive) and time to first adjudicated major adverse cardiovascular event (MACE; composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke). The study has more than 99% power for the Hb non-inferiority (NI) test with an NI margin of -0.75 g/dL for the treatment difference of mean change in Hb between baseline and EP, and approximately 90% power to exclude the NI margin of 1.25 for time to first adjudicated MACE, for daprodustat compared with darbepoetin alfa. Conditional on both co-primary endpoints achieving NI at the one-sided 2.5% level, statistical testing will progress to evaluate MACE and the principal secondary endpoint of CKD progression for superiority. These tests will be multiplicity adjusted. Results A total of 3872 patients were randomised (median age 67 years, 56% female; 55% white, 28% Asian, and 10% black). The median baseline Hb was 9.8 g/dL, serum ferritin was 274 ng/mL, TSAT 30%, and eGFR 18 mL/min/1.73 m2. Among randomised patients, 54% were ESA non-users, 57% reported a history of diabetes mellitus and 36% a history of cardiovascular disease. Median blood pressure was 135/74 mmHg. Sixty percent of participants were taking angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, while 57% were taking lipid modifying agents at baseline. The trial is expected to complete during 2021. Conclusion ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not requiring dialysis.

Understanding submucosal electrosurgery for the treatment of nasal turbinate enlargement

2006 ◽  
Vol 121 (7) ◽  
pp. 615-622 ◽  
Author(s):  
S E J Farmer ◽  
R Eccles
Keyword(s):  
Clinical Trials ◽  
Surgical Management ◽  
Inferior Turbinate ◽  
Efficacy And Safety ◽  
Safety And Efficacy ◽  
Nasal Turbinate ◽  
History Of ◽  
Turbinate Reduction ◽  
Tissue Reduction ◽  
Made In

The surgical management of inferior turbinate enlargement is controversial. Submucosal electrosurgical techniques for turbinate reduction include conventional diathermy, radiofrequency tissue reduction and coblation. All electrosurgical techniques use radiofrequency electricity to damage turbinate tissue but differ in the control and delivery of energy. This review will examine the history of submucosal electrosurgery and clarify the various techniques. This review will also examine the evidence for the efficacy and safety of electrosurgery for the treatment of nasal turbinate enlargement, and will make a case that no progress will be made in clinical trials on the safety and efficacy unless there is standardisation of equipment and techniques in nasal electrosurgery.

scholarly journals Exhalation Delivery Systems for Application of Intranasal Corticosteroids

2020 ◽  
pp. 014556132098019
Author(s):  
Alexander J. Kovacs ◽  
Nithin D. Adappa ◽  
Edward C. Kuan
Keyword(s):  
Nasal Cavity ◽  
Delivery System ◽  
Paranasal Sinuses ◽  
Safety Data ◽  
Sinus Surgery ◽  
Topical Steroids ◽  
Efficacy And Safety ◽  
Open Label ◽  
Safety And Efficacy ◽  
Patient Reported

Background: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient’s forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. Methods: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. Results: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. Conclusion: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.

scholarly journals DOP73 Efficacy and safety of escalation to tofacitinib 10 mg BID for patients with UC following loss of response on 5 mg BID maintenance therapy: Results from OCTAVE open-label, long-term extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S110-S111 ◽  
Author(s):  
B E Sands ◽  
A C Moss ◽  
A Armuzzi ◽  
J K Marshall ◽  
J O Lindsay ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Treatment Failure ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Safety Data ◽  
Mucosal Healing ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References

scholarly journals A patient with severe rhabdomyolysis and high levels of creatinine kinase had renal functions fully recovered after haemodialysis: a case report

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051988810 ◽  
Author(s):  
Shang-Feng Tsai ◽  
Jun-Li Tsai ◽  
Cheng-Hsu Chen
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Predictive Power ◽  
Kidney Injury ◽  
Blood Biomarkers ◽  
History Of ◽  
Very High ◽  
Current Report

Rhabdomyolysis is diagnosed based on the levels of blood biomarkers such as creatine kinase (CK), but the use of CK levels to predict long-term renal function remains controversial. This current report presents a case with a very high CK level with the presentation of acute kidney injury (AKI) who regained full renal function. A 29-year-old man, in a manic mood and presenting with dyspnoea, was admitted to hospital following an episode of ketamine use along with a history of drug abuse. The laboratory analyses identified rhabdomyolysis (CK, 35 266 U/l) and AKI (serum creatinine, 3.96 mg/dl). Despite treatment with intravenous normal saline (4000 ml/day), his CK level reached at least 300 000 U/l. He underwent 13 sessions of haemodialysis and his renal function fully recovered. The final measurements were serum creatinine 1.0 mg/dl and CK 212 U/l. These findings support the view that the predictive power of CK level on AKI is limited, especially regarding long-term renal function. Close follow-up examinations of renal function after haemodialysis are mandatory for patients with rhabdomyolysis.

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

scholarly journals Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

2011 ◽  
Vol 154 (3) ◽  
pp. 387-397 ◽  
Author(s):  
Elliott Vichinsky ◽  
Françoise Bernaudin ◽  
Gian Luca Forni ◽  
Renee Gardner ◽  
Kathryn Hassell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Safety And Efficacy

Safety and Efficacy of High Dose Intravenous Desferoxamine for Reduction of Iron Overload Due to Chronic Transfusion in Sickle Cell Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1430-1430
Author(s):  
Ram Kalpatthi ◽  
Brittany Peters ◽  
David Holloman ◽  
Elizabeth Rackoffe ◽  
Deborah Disco ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Liver Tissue ◽  
Iron Concentration ◽  
P Value ◽  
High Dose ◽  
Liver Iron ◽  
Iron Storage

Abstract Background: Patients with sickle cell disease (SCD) receiving chronic blood transfusions are at risk of developing iron overload and organ toxicity. Chelation therapy with either subcutaneous (SQ) desferoxamine (DFO) or oral deferasirox is effective in preventing and reducing iron overload but poses significant challenges with patient compliance. Intravenous (IV) infusions of high dose DFO (HDD) have been utilized in non compliant patients with heavy iron overload in small case series. We review our experience of high dose IV DFO in a large cohort of SCD patients with significant iron overload who are non compliant with SQ DFO. Methods: The medical records of SCD patients who received HDD in our center between 1993 and 2004 were reviewed. All of them were on chronic transfusion, had significant iron overload defined by serum ferritin &gt; 1500 and/or liver iron concentration (LIC) more than 10 μg/g of liver tissue and were non-compliant with SQ DFO. All patients underwent annual ophthalmologic, hearing, pulmonary and cardiac evaluation. Demographic data, treatment details, serum ferritin levels, liver iron concentration (LIC), liver enzymes, renal function tests, audiogram and other relevant clinical data were collected. Results: There were 27 patients (19 males, 8 females), 19 patients were on transfusion for history of cerebrovascular accident, 5 for abnormal transcranial Doppler flow velocity, 2 for transient ischemic attack and one for recurrent pain crises. All continued to receive packed red blood cell transfusions aimed to keep HbS levels below 30 or 50% during this time. They were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hrs every 2 weeks (20 patients), 3 weeks (4 patients) and 4 weeks (3 patients). The mean age at start of high dose regimen was 14.6 years (range 9–27 years). The mean duration of HDD treatment was 8.9 months (range 3–49 months). Fourteen patients had LIC determined by liver biopsy. Significant reductions in LIC were observed after HD (table I). This was more pronounced in patients who had higher LIC and received at least 6 months of HDD. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Four patients had portal triaditis initially which resolved after starting HDD therapy. Also there was significant improvement in liver enzymes (ALT, AST) after HDD. There was a trend in decreasing ferritin levels after HDD but this did not achieve statistical significance. All patients tolerated HDD without any major reactions. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. Blood urea nitrogen remained normal in all patients after HDD but there was mild increase in serum creatinine. One patient had high serum creatinine (1.2 mg/dL) after two doses HDD. This patient had focal segmental glomeurosclerosis which was most probably the cause for the rise in creatinine. There was no significant increase in serum creatinine in our series when this patient was excluded. Conclusions: In our cohort of SCD patients we observed a significant decrease in liver iron burden with high dose IV DFO. Our patients tolerated the therapy well without any major toxicity. This regimen is safe and may be an option for poorly compliant patients with significant iron overload. In addition, combination of this regimen with oral iron chelators may be of benefit to patients with significant iron overload and organ dysfunction. Table 1: Laboratory characteristics of sickle cell patients before and after high dose IV DFO Parameter No. of Patients Mean (SD) prior to HDD Mean (SD)after HDD p Value* * Changes in mean levels analyzed using two-tailed Paired T Test with significant p value ≤ 0.05. SD – Standard deviation + See text Liver iron (μg/g of liver tissue ) 14 16864 (10903) 12681 (8298) 0.04 Liver iron min of 6 months of HDD (μg/g of liver tissue ) 8 18677 (8319) 9362 (4521) 0.01 Liver iron &gt;10 mg & minimum 6 months of HDD (μg/g of liver tissue) 7 21181 (7054) 10092 (4443) 0.01 Grade of liver iron storage 14 3.57 (0.9) 3.07 (1) 0.05 Serum Ferritin (ng/mL) 27 3842 (2619) 3238 (1780) 0.06 Serum AST (IU/L) 27 54.1 (27.2) 44.6 (17.6) 0.04 Serum ALT (IU/L) 27 39.2 (36) 27.5 (14.2) 0.01 Blood urea nitrogen (mg/dL) 27 8.9 (2.9) 9.5 (4.3) 0.20 Serum Creatinine (mg/dL)+ 26 0.50 (0.1) 0.55 (0.2) 0.07

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