A Prospective Observational Multicenter Study on Deferiprone & Deferasirox in Clinical Practice of Pediatric Patients with Transfusion-Dependent B-Thalassemia

Abstract Background: Iron overload is inevitable but a manageable complication of frequent blood transfusion, the effectiveness and safety of two iron chelation therapy in young children with transfusion-dependent B thalassemia (TDB-T) using either deferiprone (DFP) or deferasirox (DFX) were well studied in clinical trials. The primary objectives were; reporting efficacy and frequency of all adverse events (AEs) as compared with published data. Secondary objective was reporting deviation from guidelines, The analysis of clinical data is the first step to design new strategies Methodology: An investigator initiated 2-year multicenter prospective study enrolling over 6 months period; 302 children with TDB-T from 11 centers; keeping pre-transfusion Hb >8gm/dl. When serum ferritin (SF) reached around 1000 ng/ml; they had received according to availability; either DFP liquid solution in a dose; 75 mg/kg/day (n=62) or DFX (n=240); (dispersed tablet; 25% or film-coated tablet 75% in a dose; 20-25 mg/kg/d or its equivalent). CBC was done biweekly in DFP and pre-transfusion in DFX group. Liver transaminases, serum creatinine and (SF) were done /3 months. Changes in growth velocity over time were documented. Results: 66% were males, age at enrolment was; (11-19 and 14-26 months) in DFP and DFX respectively; they had received (6-8) and (7-11) transfusions prior to chelation in both groups respectively in addition to (16-21) during the study. 20% of patients did not achieve the target pre-transfusion Hb level. At initiation of DFP; SF median; 960 (IQR; 122 ng/ml) while those on DFX had SF; median 1070 (IQR 138 ng/ml) both groups had comparable transfusion iron input during the study. At 24 months of regular transfusion-chelation; SF < 1000 ng/ml was noticed in 65% and 60% of the patients respectively with good growth velocity in children using either chelator. Unnecessary over-dosing of DFX > 40 mg/kg was observed in 5%, meanwhile 3.2% had received DFP in a dose >75-100 mg/kg while SF was <1500 ng/ml. Under-reporting of adverse events in both groups was observed; 5% GIT upset, neither arthralgia nor agranulocytosis, neutropenia (3.2%) in DFP group and CBC was not checked biweekly; but only prior to transfusion. 4-5 % had elevated transaminases in both chelators, while patients on DFX reported; GIT upset in 4.2% and rash in 1.6%. Elevated serum creatinine > 33% from baseline on 2 successive visits was observed in 5% in DFX without reducing the dose or re-check. No unexpected, serious severe adverse events were reported in both groups. Poorly controlled patients with SF > 1500 ng /ml at 12 or 24 months were 12, 8% in DFP group; in contrast to 15%, 10% in DFX group respectively; with no statistical difference; (compliance was comparable). The total DFP and DFX discontinuation ratio was 5% in each group. Conclusion: infants and young children with TDB-T naïve to chelation were put on mono-therapy at younger age than reported before. Both chelators were effective, well tolerated and with no severe safety concerns; however deviation from guidelines was observed as; unnecessary over-dosing of DFX and under-reporting of AEs in both groups in real life practice. Disclosures Hamdy: ApoPharma: Honoraria; Amgen: Honoraria; Bayer: Honoraria; Novartis: Honoraria; NovoNordisk: Honoraria; Roche: Honoraria; Takeda: Honoraria.

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A Prospective Randomized Multicenter Trial Using Either Deferiprone or Deferasirox after an Early Start of Deferiprone or Placebo in Young Children Newly Diagnosed with Transfusion-Dependent Beta-Thalassemia

Blood ◽

10.1182/blood-2021-149359 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3071-3071

Author(s):

Mohsen Saleh Elalfy ◽

Amira Adly ◽

Fatma Soliman Elsayed Ebeid ◽

Amal El-Beshlawy ◽

Neveen Salama ◽

...

Keyword(s):

Young Children ◽

Iron Overload ◽

Growth Velocity ◽

Chelation Therapy ◽

Elevated Serum ◽

Iron Chelation ◽

Beta Thalassemia ◽

P Value ◽

Growth Enhancement ◽

Early Start

Abstract Iron overload is a potentially preventable complication of blood transfusion dependency. The effectiveness and safety of early start of iron chelation therapy in young children with transfusion-dependent Beta-thalassemia (TDB-T) prior to development of iron overload have been recently demonstrated. The aim of this study was to evaluate the long term effectiveness and safety of continued iron chelation in these children. Methodology: This is a multi-center, investigator initiated, one year prospective randomized study of children with TDB-T who completed the randomized START study (NCT03591575), which had evaluated the safety and efficacy of the oral iron chelator (DFP) in children who did not yet meet the criteria for starting chelation therapy as per standard practice. Enrolment is shown in follow-up chart below; 48 children with TDBT from 3 centers were eligible to be enrolled and were randomized in 1:1 ratio to receive either DFP (n=23) or deferasirox (DFX) (n=25). Half of patients in this study were naïve to chelation (on placebo in START study); had received DFP at a dose; 75 mg/kg/ day or DFX in a dose; 20-25mg/kg/d in 2:1 ratio respectively, while those on DFP in START had continued on either DFP or DFX in 1:2 ratio with same doses. Patients were kept on regular transfusion to keep pre-transfusion Hb >8gm/dl. The primary endpoint was safety and secondary endpoints were changes in serum ferritin (SF) and growth enhancement (height, weight) both were assessed quarterly. An informed consent was signed by parents of all patients before start of the study. Statistical significance between DFP and DFX treated groups was calculated via t-test for continuous variables and Fisher's exact test for discrete variables. Results: In the current study; 66% of the children were males, at enrolment; their age ranged from 20-68 (median 38) months; those who were on DFP or placebo in START had received comparable transfusion units (median 11 and 9 respectively) and SF (880 and 1150 ng/ml respectively). At 12 month of continuation on iron chelation 22% and 60% of children on DFP vs 12% and 48% of those on DFX had SF<500 ng/ml or 500- <1000 ng/ml, respectively (p value <0.05);. TDB-T initiated and continued on DFP had the best growth velocity; all had annual growth velocity >5cm (p value <0.01), as well as a significant lower final SF (P value < 0.01). Adverse events were mild and uncommon in both groups. There were no episodes of arthralgia or agranulocytosis in either group. Elevated serum creatinine > 33% from baseline on 2 successive visits were observed in 0% in DFP vs. 12% in DFX. No unexpected, serious, or severe AEs were reported in both groups. Conclusion: Children with TDB-T whether on DFP or DFX showed uncommon mild AEs, with no serious or severe AEs. Patients on DFP after an early start of DFP showed adequate growth velocity and better control of iron-overload on serial measurement of SF; compared with those who were on placebo. Figure 1 Figure 1. Disclosures Hamdy: ApoPharma: Honoraria; Amgen: Honoraria; Bayer: Honoraria; Novartis: Honoraria; NovoNordisk: Honoraria; Roche: Honoraria; Takeda: Honoraria.

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Chemoradiotherapy With Generic Cisplatin Formulations for Head and Neck Cancers

Japanese Clinical Medicine ◽

10.1177/1179670717749231 ◽

2018 ◽

Vol 9 ◽

pp. 117967071774923

Author(s):

Rie Shimada ◽

Kiyoaki Tsukahara ◽

Soichiro Takase ◽

Isaku Okamoto ◽

Hiroki Sato ◽

...

Keyword(s):

Head And Neck Cancer ◽

Adverse Events ◽

Serum Creatinine ◽

Head And Neck ◽

Concurrent Chemoradiotherapy ◽

Generic Drugs ◽

Elevated Serum ◽

Completion Rates ◽

Elevated Serum Creatinine ◽

Grade 3

The use of generic drugs has been increasing. However, studies of the safety of generic cisplatin (CDDP) for the treatment of head and neck cancer (HNC) have not been reported. This study investigated the treatment completion rates and incidence of CDDP-related adverse events in patients with advanced HNC treated with concurrent chemoradiotherapy (CRT) using generic CDDP. This study included 72 patients who received concurrent CRT using generic CDDP. The number of courses of CDDP was 3 in 45 patients, 2 in 19 patients, and 1 in 8 patients. During 154 courses of 80 mg/m2 generic CDDP, grade 3/4 leukopenia in 21 (14%), neutropenia in 18 (12%), and hypochromia in 8 (5%) cases were reported. Grade 2 elevated serum creatinine occurred in 4 cases (3%), but no grade 3/4 elevated serum creatinine was reported. These results suggest that CRT using generic CDDP is well tolerated in patients with HNC.

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Factors Predicting Adverse Events Associated with Pregabalin Administered for Neuropathic Pain Relief

Pain Research and Management ◽

10.1155/2014/280549 ◽

2014 ◽

Vol 19 (6) ◽

pp. e164-e167 ◽

Cited By ~ 4

Author(s):

Yuko Kanbayashi ◽

Keiko Onishi ◽

Toyoshi Hosokawa

Keyword(s):

Neuropathic Pain ◽

Regression Analysis ◽

Weight Gain ◽

Adverse Events ◽

Serum Creatinine ◽

Serum Creatinine Level ◽

Creatinine Level ◽

Predictive Factors ◽

Elevated Serum ◽

Inflammatory Drugs

BACKGROUND:Pregabalin administration is occasionally abandoned due to adverse events such as somnolence, dizziness, unsteadiness, weight gain and edema. However, the exact causes of these differences in adverse events associated with pregabalin have not been elucidated.OBJECTIVE: To identify factors predicting adverse events associated with pregabalin administered for neuropathic pain.METHODS: The present study was a retrospective analysis involving 208 patients with neuropathic pain who had been treated with pregabalin in the pain clinic at the authors’ hospital between July 2010 and September 2011. Variables were extracted from the clinical records for regression analysis of factors related to the occurrence of adverse events associated with pregabalin administration. Multivariate logistic regression analysis was used to examine the relationship between various predictive factors and the adverse events.RESULTS: Predictive factors were: duration of therapy (OR 1.684 [95% CI 1.179 to 2.406]; P=0.0042) for somnolence; nonsteroidal anti-inflammatory drugs (OR 0.132 [95% CI 0.030 to 0.578]; P=0.0072), age (OR 3.137 [95% CI 1.220 to 8.066]; P=0.0177) and maintenance dose (OR 0.437 [95% CI 0.217 to 0.880]; P=0.0205) for unsteadiness; serum creatinine (OR 6.439 [95% CI 1.541 to 26.902]; P=0.0107) for body weight gain; and neurotropin (OR 8.538 [95% CI 1.159 to 62.901]; P=0.0353) and serum creatinine (OR 6.912 [95% CI 1.118 to 42.726]; P=0.0375) for edema.CONCLUSIONS: The results of the present study indicate that care is warranted regarding long durations of therapy for somnolence, advanced age rather than dose-dependent adverse events for unsteadiness, elevated serum creatinine level for weight gain, and elevated serum creatinine level and combination use of neurotropin for edema. The safety of the combined use of pregabalin and nonsteroidal anti-inflammatory drugs were also suggested.

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L'esperienza clinica con Levometadone nel trattamento del disturbo da uso di oppiacei

MISSION ◽

10.3280/mis52-2018oa8541 ◽

2019 ◽

pp. 54-57

Author(s):

Marco Riglietta ◽

Paolo Donadoni ◽

Grazia Carbone ◽

Caterina Pisoni ◽

Franca Colombi ◽

...

Keyword(s):

Adverse Events ◽

Real Life ◽

Opioid Use Disorder ◽

Racemic Mixture ◽

Opioid Use ◽

The Real ◽

New Formulation

In Italy, at the end of the 1970s, methadone hydrochloride was introduced for the treatment of opioid use disorder, in the form of a racemic mixture consisting of levomethadone and dextromethadone.In 2015 Levometadone was introduced, a new formulation marketed in Italy for the treatment of opioid use disorder in 2015.The article aims to bring the experience of an Italian Addiction Centre back to the use of this new formulation in the "real life" analyzing the efficacy, the trend of adverse events and pharmacological iterations in a context in which the treated population often uses besides the opiates, cocaine and alcohol, are burdened by a relevant physical and psychic comorbidity and frequently have a prescribed polypharmacy.

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Faculty Opinions recommendation of Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725998397.793512162 ◽

2015 ◽

Author(s):

Timothy Gardner

Keyword(s):

Acute Pancreatitis ◽

Serum Creatinine ◽

Pancreatic Necrosis ◽

Elevated Serum ◽

Elevated Serum Creatinine

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POS0675 THE COMPARATIVE 3-YEAR RETENTION RATE OF TARGETED-SYNTHETIC AND BIOLOGIC DRUGS FOR RHEUMATOID ARTHRITIS: REAL-LIFE DATA FROM THE ITALIAN GISEA REGISTRY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3557 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 582.1-582

Author(s):

E. G. Favalli ◽

F. Iannone ◽

E. Gremese ◽

R. Gorla ◽

R. Foti ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Retention Rate ◽

Large Population ◽

Real Life ◽

Mechanisms Of Action ◽

Biologic Drugs ◽

Real Life Setting ◽

Study Population ◽

Targeted Drug

Background:Long-term observational data on the real-life use of JAK inhibitors (JAKis) for rheumatoid arthritis (RA) and their comparison with biological drugs are still very limited. Large population-based registries have been increasingly used to investigate the performance of targeted drugs in a real-life setting.Objectives:The aim of this study is to evaluate and compare the 3-year retention rate of JAKis, TNF inhibitors (TNFis) and biologic drugs with other mechanisms of action (OMAs) in the large cohort of RA patients included in the Italian national GISEA registry.Methods:Data of all RA patients treated with targeted synthetic or biologic drugs were prospectively collected in the Italian multicentric GISEA registry. The analysis was limited to patients who started a first- or second-line targeted drug in the period after the first JAKi was marketed in Italy (1st December 2017). The 3-year retention rate was calculated by the Kaplan-Meier method and compared between different drug classes by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 1027 RA patients (79.8% females, mean age [±SD] 56.9 [±13.5] years, mean disease duration 9.8 [±9] years, mean baseline SDAI 17.5 [±11.9], ACPA positive 67.4%, RF positive 62.7%) who received JAKis (baricitinib or tofacitinib, n=297), TNFis (n=365), or OMAs (n=365) as first or second targeted drug. Main baseline characteristics of study population were overall well balanced between treatment groups. Retention rate was numerically but not statistically higher (p=0.18) in patients treated with JAKis compared with TNFis or OMAs (80.6, 78.9 and 76.4% at 1 year and 73, 56.8 and 63.8% at 3 years, respectively) (Figure 1). Drug survival was significantly higher in patients receiving concomitant methotrexate (MTX) compared with monotherapy only in TNFis (66.8 vs 47.1%, p=0.04) but not in JAKis (76.1 vs 70.1%, p=0.54) and OMAs (66.1 vs 61.9%, p=0.41) group. Therapy was discontinued in a total of 211 patients because of ineffectiveness (n=107), adverse events (n=88), or compliance/other reasons (n=16). The most frequent reason for treatment withdrawal was ineffectiveness in both JAKis (n=30 out of 56) and TNFis (n=45 out of 74) groups, whereas OMAs were discontinued more frequently because of adverse events (n=41 out of 81).Conclusion:Our data confirmed in a real-life setting a favorable 3-year retention rate of all available targeted mechanisms of action for RA therapy. As expected, concomitant MTX significantly impacted persistence on therapy of TNFis only. Discontinuations of JAKis for adverse events were infrequent overall, confirming the safety profile observed in randomized clinical trials.Figure 1.Three-year retention rate by treatment groupDisclosure of Interests:None declared

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The Irish National Adverse Event Study-2 (INAES-2): longitudinal trends in adverse event rates in the Irish healthcare system

BMJ Quality & Safety ◽

10.1136/bmjqs-2020-011122 ◽

2021 ◽

pp. bmjqs-2020-011122 ◽

Cited By ~ 1

Author(s):

Warren Connolly ◽

Natasha Rafter ◽

Ronan M Conroy ◽

Cornelia Stuart ◽

Anne Hickey ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Positive Impact ◽

Retrospective Chart Review ◽

Published Data ◽

National Programmes ◽

Event Rates ◽

Hospital Associated Infections ◽

Design And Methods ◽

The Impact

ObjectivesTo quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009.Design and methodsA retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009.ResultsThe percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01).ConclusionAdverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.

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Tildrakizumab Inadequate Responders Switching to an Alternative IL-23 Inhibitor: A Case Series

Journal of Psoriasis and Psoriatic Arthritis ◽

10.1177/24755303211037308 ◽

2021 ◽

pp. 247553032110373

Author(s):

Eingun James Song ◽

Audrey Jia Shin Wong

Keyword(s):

Adverse Events ◽

Expert Opinion ◽

Case Series ◽

Tnf Alpha ◽

Published Data ◽

Inadequate Response ◽

Limited Time ◽

Case Description ◽

Single Institution ◽

Inadequate Responders

Background: Biologic switching is not uncommon in the treatment of psoriasis and is most often due to inadequate response of adverse events. Staying within or switching out of the class is still based on expert opinion but there are published data on intra-class switching with TNF-alpha and IL-17 inhibitors. Less is known about the IL-23 inhibitors because of their limited time in the market. We would like to present our experience with inadequate responders to tildrakizumab, a selective IL23 inhibitor, who were switched to an alternative IL-23 inhibitor. Case Description: This is a case series of 6 patients at a single institution considered inadequate responders to tildrakizumab, which included primary failures, secondary failures, and intermediate responders, who were subsequently switched to another IL-23 inhibitor. Conclusion: All 6 patients who were inadequate responders to tildrakizumab showed significant improvement after switching to another IL-23 inhibitor, with 5/6 reaching IGA 0/1 after 16 weeks of treatment.

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Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

RMD Open ◽

10.1136/rmdopen-2020-001519 ◽

2021 ◽

Vol 7 (1) ◽

pp. e001519

Author(s):

Roberta Ramonda ◽

Mariagrazia Lorenzin ◽

Antonio Carriero ◽

Maria Sole Chimenti ◽

Raffaele Scarpa ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Adverse Events ◽

Disease Activity ◽

Biological Treatment ◽

Retention Rate ◽

Real Life ◽

Drug Retention ◽

Group A ◽

Group B ◽

Drug Retention Rate

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) diﬀerences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

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