scholarly journals Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Tomas Walhelm ◽  
Iva Gunnarsson ◽  
Rebecca Heijke ◽  
Dag Leonard ◽  
Estelle Trysberg ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Experience ◽  
Lupus Erythematosus ◽  
Immunosuppressive Agents ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Complement Protein ◽  
Cell Counts ◽  
Over Time

As treatment options in advanced systematic lupus erythematosus (SLE) are limited, there is an urgent need for new and effective therapeutic alternatives for selected cases with severe disease. Bortezomib (BTZ) is a specific, reversible, inhibitor of the 20S subunit of the proteasome. Herein, we report clinical experience regarding efficacy and safety from all patients receiving BTZ as therapy for SLE in Sweden during the years 2014−2020. 8 females and 4 males were included with a mean disease duration at BTZ initiation of 8.8 years (range 0.7–20 years). Renal involvement was the main target for BTZ. Reduction of global disease activity was recorded by decreasing SLEDAI-2K scores over time and remained significantly reduced at the 6-month (p=0.007) and the 12-month (p=0.008) follow-up visits. From BTZ initiation, complement protein 3 (C3) levels increased significantly after the 2nd treatment cycle (p=0.05), the 6-month (p=0.03) and the 12-month (p=0.04) follow-up visits. The urine albumin/creatinine ratio declined over time and reached significance at the 6-month (p=0.008) and the 12-month follow-up visits (p=0.004). Seroconversion of anti-dsDNA (27%), anti-C1q (50%) and anti-Sm (67%) was observed. 6 of 12 patients experienced at least one side-effect during follow-up, whereof the most common adverse events were infections. Safety parameters (C-reactive protein, blood cell counts) mainly remained stable over time. To conclude, we report favorable therapeutic effects of BTZ used in combination with corticosteroids in a majority of patients with severe SLE manifestations irresponsive to conventional immunosuppressive agents. Reduction of proteinuria was observed over time as well as seroconversion of some autoantibody specificities. In most patients, tolerance was acceptable but mild adverse events was not uncommon. Special attention should be paid to infections and hypogammaglobinemia.

scholarly journals SAT0525 EFFICACY AND SAFETY OF MZR FOR IgG4-RELATED DISEASE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1219-1220
Author(s):  
S. Kawaai ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
H. Ozawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Retention Rate ◽  
Case Reports ◽  
Efficacy And Safety ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Number Of Patients ◽  
Serum Igg4 ◽  
Over Time

Background:IgG4-Related Disease (IgG4RD) is known to cause multiple organ lesions with infiltration of IgG4-positive plasma cells, and patients often have relapses with tapering treatments despite an initial good response to glucocorticoids therapy. Mizoribine (MZR) is an immunosuppressant working as an inhibitor of purine synthesis, which mechanism of action is similar to mycophenolate mofetil. Data regarding the efficacy and safety of MZR on IgG4RD is limited although some previous case reports1showed effectiveness for IgG4RD.Objectives:This study aims to assess the efficacy and safety of MZR in patients with IgG4RD.Methods:We retrospectively reviewed charts of IgG4RD patients who used MZR between January 2004 and December 2019 at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. We investigated basic demographics, involved organs, results of blood tests including IgG and IgG4 titer, and medications used including glucocorticoid and other immunosuppressants (IS). We followed IgG4 titer, dose of glucocorticoid, flare of disease and retention of MZR at the beginning, 6 and 12months after starting MZR. We compared changes in PSL (prednisolone) doses and IgG4 titers over time using Friedman test with Bonferroni correction. We also checked adverse events during follow up.Results:Twenty-two patients with IgG4RD who used MZR were included. Median age was 62 years old, and 15 (68.2%) patients are male. Lacrimal and salivary glands, pancreatitis and retroperitoneal fibrosis were common lesions. All patients were initially treated with glucocorticoids. Flare was observed in 5 (22.7 %) patients before initiation of MZR. The number of patients who continued MZR without flare are 19 (86.4 %) at 6 months, and 14 (73.7 %) at 12 months. IgG4 titer significantly declined at 6 and 12 months from baseline although significant consecutive decrease in PSL dose (Figure 1, 2). Liver dysfunctions are commonest adverse events (n=16, 72.7%) but mild (grade1; n=15, 68.2%) and most cases are apparently due to other reasons. Serious infection (SI) occurred in 3 (13.6%) patients in total follow up, however no SI were observed during 1 year after MZR treatment.Conclusion:MZR can be safely used in patients of IgG4RD with high retention rate, and seemed to have steroid-sparing effect. Prospective comparative studies are needed.References:[1]Nanke Y, Kobashigawa T, Yago T, Kamatani N, Kotake S. A case of Mikulicz’s disease, IgG4-related plasmacytic syndrome, successfully treated by corticosteroid and mizoribine, and then by mizoribine alone. Intern Med 49: 1449-1453, 2010.Table 1.Patient characteristics    Table 2.Disease and treatment status before and after initiation of MZR    Figure 1.Serum IgG4 level changesFigure 2.Changes in the PSL dose over timeDisclosure of Interests:None declared

scholarly journals Hydroxychloroquine versus tacrolimus for the treatment of persistently active systemic lupus erythematosus

2021 ◽  
Author(s):  
Masahiro Ayano ◽  
Yasutaka Kimoto ◽  
Hiroki Mitoma ◽  
Mitsuteru Akahoshi ◽  
Nobuyuki Ono ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Adverse Events ◽  
Treatment Failure ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Immunosuppressive Agents ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Low Disease Activity ◽  
Free Survival

ABSTRACT Objectives We aimed to reveal the effectiveness of hydroxychloroquine (HCQ) compared with tacrolimus (TAC), an immunosuppressive agent, in patients with systemic lupus erythematosus (SLE) with persistent activity on standard treatment. Methods We retrospectively compared the efficacy and safety of the treatment between 18 patients receiving HCQ and 27 patients receiving TAC. None of the patients were in the lupus low disease activity state (LLDAS) at the beginning of this study. The efficacy end points were the cumulative incidence of LLDAS attainment without additional immunosuppressive agents, drug continuation rate, and treatment failure–free survival. The safety end point was the frequency of adverse events. Results Eight (44.4%) patients in the HCQ group and 10 (37.0%) patients in the TAC group achieved LLDAS during the follow-up period; thus, the cumulative incidences of LLDAS attainment of the two treatments were nearly identical. The drug continuation and treatment failure–free survival rates were also not different between the two groups. The frequency of adverse events showed no clear differences between the two groups. Conclusions The efficacy and safety of an add-on treatment with HCQ are similar to those with TAC. Patients with persistently active SLE can benefit from HCQ in efforts to achieve at least low disease activity.

scholarly journals POS0204 AUTOANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA THERAPY IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.1-318
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
F. Oliveira Pinheiro ◽  
M. Rato ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Disease Duration ◽  
Seroconversion Rate ◽  
Necrosis Factor Alpha ◽  
Malar Rash ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Over Time

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared

OP270 Why The Haute Autorité de Santé Rejects the Widespread Use Of “Mini-Bypass”/One Anastomosis Gastric Bypass For Obesity In France

2020 ◽  
Vol 36 (S1) ◽  
pp. 4-4
Author(s):  
Jean-Charles Lafarge ◽  
Denis-Jean David ◽  
Cédric Carbonneil
Keyword(s):  
Esophageal Cancer ◽  
Gastric Bypass ◽  
Adverse Events ◽  
Severe Obesity ◽  
One Anastomosis Gastric Bypass ◽  
Close Monitoring ◽  
Efficacy And Safety ◽  
Multicenter Rct ◽  
Nutritional Complications

IntroductionOne anastomosis gastric bypass (OAGB) has become a widespread technique over the last few years in France, without any prior assessment and despite existing controversies among bariatric surgeons. An older bypass technique for treating obesity, the Roux-en-Y gastric bypass (RYGB), is available and reimbursed, having been assessed and approved for use in 2005. In 2019, the French Haute Autorité de Santé (HAS) assessed OAGB for the treatment of severe and massive obesity. This assessment, the first in the world, was undertaken for OAGBs carried out with a 200- or 150-centimeter biliopancreatic-limb (BP-limb) length.MethodsA systematic review (SR) of the literature and consultation of a working group consisting of both healthcare professionals (clinician and surgeons) and patients were carried out. The primary aim of our assessment was to determine whether the OAGB technique can replace RYGB. The efficacy and safety profile of OAGB was compared with RYGB in adult patients with massive, severe obesity. Complications and postoperative follow up specific to OAGB were identified.ResultsThe three selected randomized controlled trials (RCTs) could not confirm the superiority or the non-inferiority of OAGB, compared with RYGB, on the selected efficacy endpoints of weight loss, resolution of comorbidities, and quality of life. Adverse events reported for OAGB included severe nutritional complications and bile reflux that could potentially lead to lower esophageal cancer. In one RCT, the frequency of serious adverse events in the OAGB group was almost two times higher than in the RYGB group.ConclusionsHAS considered that OAGB carried out with a longer (200 centimeter) BP-limb is not a validated technique for the surgical treatment of massive, severe obesity. Thus, it cannot be considered an alternative to RYGB. There were insufficient data available on OAGB performed with a 150-centimeter BP-limb. Thus, HAS recommended undertaking a multicenter RCT to assess the efficacy and safety of OAGB. Patients who have already undergone OAGB should receive the same follow up as patients who have received RYGB, including close monitoring for nutritional complications and lower esophageal cancer and an endoscopic examination five years after surgery.

scholarly journals Efficacy and safety of combined endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous occlusion (BRTOcc) of gastrorenal shunts in patients with bleeding gastric fundal varices

2020 ◽  
Author(s):  
Fateh Bazerbachi ◽  
Akira Dobashi ◽  
Swarup Kumar ◽  
Sanjay Misra ◽  
Navtej S Buttar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gastric Varices ◽  
High Rate ◽  
Efficacy And Safety ◽  
Cyanoacrylate Glue ◽  
Serious Adverse Events ◽  
Gastroesophageal Varices ◽  
Life Threatening ◽  
Glue Embolization

Abstract Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.

scholarly journals Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Saori Fukui ◽  
Mitsuru Seki ◽  
Takaomi Minami ◽  
Kazuhiko Kotani ◽  
Kensuke Oka ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Link Type ◽  
Cell Counts ◽  
Infusion Speed ◽  
Ivig Administration

Abstract Background High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. Methods This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. Results A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). Conclusion The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). Trial registration University Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058

scholarly journals Efficacy and safety of a combined treatment of sodium stibogluconate at 20mg/kg/day with upper maximum daily dose limit of 850mg and Paromomycin 15mg/kg/day in HIV negative visceral leishmaniasis patients. A retrospective study, northwest Ethiopia

2021 ◽  
Vol 15 (8) ◽  
pp. e0009713
Author(s):  
Aschalew Tamiru ◽  
Rezika Mohammed ◽  
Saba Atnafu ◽  
Girmay Medhin ◽  
Asrat Hailu
Keyword(s):  
Visceral Leishmaniasis ◽  
Adverse Events ◽  
Combined Treatment ◽  
Daily Maximum ◽  
Sodium Stibogluconate ◽  
Efficacy And Safety ◽  
African Countries ◽  
Treatment Interruptions ◽  
Hiv Negative

Background Visceral leishmaniasis (VL) is one of the most neglected tropical infectious diseases. It is fatal if left untreated. The objective of this study was to assess the efficacy and safety of 17-day injections of combined regimen of sodium stibogluconate and paromomycin (SSG/PM) in HIV-negative VL patients. Methods A retrospective analysis of medical records of VL patients treated in the University of Gondar Hospital during period 2012–2019 was carried out. Results A total of 2836 patients were treated for VL from 2012 to 2019. Of these 1233 were treated with SSG-PM, and 1000 of them were included in the study. Initial cure was achieved in 922 (92.2%) patients. The frequency of treatment failure, treatment interruptions, default and deaths respectively were 30 (3%), 20 (2%), 13 (1.3%) and 15 (1.5%). Among 280 patients who completed 6-month follow up, the final cure was 93.9% (263/280), 4 (1.4%) relapsed and 13 (4.6%) developed post-kala-azar dermal leishmaniasis (PKDL). The most common adverse events (AEs) were raised liver transaminases (35.1%; 351 patients), injection site pain (29.1%, 291 patients) and raised serum alpha-amylase (29.1%, 291 patients). Factors associated with poor treatment outcomes were sepsis, pneumonia, and adverse events. Conclusion A combination of SSG at 20mg/kg with upper daily maximum dose of 850mg and PM was effective for achieving initial cure at end of treatment and safe for treatment of HIV negative VL patients in northwestern Ethiopia. Our data are consistent with previous reports and confirms effectiveness of SSG/PM treatment regimen in the Eastern African countries. Efficacy at 6-months (93.9%) was estimated on data derived from patients who completed follow up and needs to be interrogated by future studies.

scholarly journals THALIDOMIDE FOR PATIENTS WITH THALASSEMIA INTERMEDIA: A RETROSPECTIVE MULTICENTER CLINICAL STUDY

2020 ◽  
Vol 12 (1) ◽  
pp. e2020021
Author(s):  
Kun Yang ◽  
Yi Wu ◽  
Yali Zhou ◽  
Tianhong Zhou ◽  
Li Wang ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Laboratory Data ◽  
Drug Discontinuation ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Thalassemia Intermedia ◽  
Short Term ◽  
Long Term Follow Up

Objective: This study focused on the efficacy and safety of thalidomide for patients with thalassemia intermedia (TI) in a multicenter trial. Methods：Clinical and laboratory data of 62 patients subjected to thalidomide therapy in four centers were retrospectively analyzed. We evaluated the efficacy and safety of thalidomide in the short-term (three months) and long-term follow-up (12 and 24 months). Response to thalidomide was defined as follows: Main Responder (MaR) showing an increase in Hb level of >2.0 g/dl or removal from blood transfusion and Minor Responder (MiR) achieving elevated hemoglobin (Hb) level of 1.0-2.0 g/dl or ≥50% reduction in blood transfusion frequency. Results：The overall response rate (ORR) of 62 patients with TI was 93.5% (58/62), with MaR and MiR rates accounting for 62.9% (39/62) and 30.6% (19/62) in short-term follow-up and 66.1% (41/62) and 27.4% (17/62) in long-term follow-up, respectively. The clinical response during long-term follow-up was maintained and the Hb level remained stable during the observation period. The response was still observed in patients with dose reduction despite a slight decrease in Hb level. However, Hb decreased rapidly to the baseline level after drug discontinuation. No effect of thalidomide on spleen size in nonsplenectomized patients was evident. Minimal side-effects were documented throughout, except peripheral neurotoxicity in one patient. Nevertheless, the mean serum ferritin (SF) level was significantly increased after treatment. Conclusion: Thalidomide had significant therapeutic effects on patients with TI, and the response was sustained with acceptable short-term and long-term adverse reactions. While these preliminary results support the potential long-term efficacy and safety of thalidomide as a therapeutic agent for TI, several issues need to be addressed before its application in the clinic.

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 884-893 ◽  
Author(s):  
M. Domenica Cappellini ◽  
Mohamed Bejaoui ◽  
Leyla Agaoglu ◽  
Duran Canatan ◽  
Marcello Capra ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Efficacy And Safety ◽  
Liver Iron ◽  
Median Serum

Abstract Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.

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