Off-label use of the expensive orphan drug eculizumab in France 2009–2013 and the impact of literature: focus on the transplantation field

Castañeda-Sanabria, Johann; Hajage, David; Jouan, Melisande Le; Perozziello, Anne; Tubach, Florence

doi:10.1007/s00228-016-2027-z

Cited by 13 publications

(11 citation statements)

References 60 publications

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“…34 A recent study in France reported close to 80% of off-label eculizumab use was due to hemolytic anemias including HUS. 35 In our study, it was also the third most common diagnosis among OLDU applications and responsible for >85% of offlabel eculizumab use. Meanwhile, the drug acquired approval towards the end of this study period in October 2015 and started to be used as labelled.…”

Section: Discussionmentioning

confidence: 54%

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data

et al. 2020

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Background. Children constitute a special population for off-label drug use (OLDU), yet limited drug-focused data exist regarding pediatric OLDU in clinical practice. This study aimed to investigate pediatric OLDU practice and compare it with pediatric drug utilization patterns of routine prescribing data. Methods. This cross-sectional study examined all approved pediatric OLDU applications, compared with electronic prescription data on national Prescription Information System of Turkish Medicines and Medical Devices Agency in 2015. OLDU applications and prescriptions were analyzed for demographic characteristics, healthcare/socioeconomic indices as well as details of drugs and diagnoses. Results. We found 7,896 OLDU applications and 7,029,512 prescriptions for the pediatric population in 2015. OLDU applications and prescriptions were mostly practiced for `2-11-year-old` children (52.7% vs. 63.4%, respectively; p < 0.01). OLDU applications and prescriptions were detected to have a positive correlation with socio-economic development index (r = 0.45, p < 0.0001 and r: 0.40, p = 0.0002; respectively) and the physician density (r = 0.66, p < 0.0001 and r: 0.43, p < 0.0001; respectively). In addition, OLDU was also positively correlated with the number of hospital beds per province (r = 0.39, p = 0.0003). Antineoplastic/immunomodulating agents were the most commonly applied drug category in OLDU (47.0%), compared with respiratory system drugs (36.6%) in routine prescribing. Eculizumab (6.5%), mycophenolate (5.6%), and canakinumab (4.4%) were the top drugs used as off-label. OLDU applications and routine prescription data revealed the most frequent diagnosis as `I27-other pulmonary heart diseases` (7.4%) and `J06-acute upper respiratory infections` (12.6%), respectively. Conclusions. This is the first nationwide study to show indication- and drug-centered aspects of pediatric OLDU and prescribing practice. Though OLDU applications is overall consistent with routine clinical practice in terms of demographics and institutional capacity, substantial variations exist regarding main drug classes and diseases. Our findings are expected to shed light on interventions focused on improving `indicated` pediatric use of drugs currently applied as off-label.

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Section: Discussionmentioning

confidence: 54%

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data

et al. 2020

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“…Subsequently, it received approval for the neuromuscular disease generalized myasthenia gravis ( 120 ) in 2017 ( 121 ) and the eye disorder neuromyelitis optica ( 122 ) in 2019 ( 123 ). Currently, eculizumab is assessed or used off-label in a range of other indications ( 124 ), such as cold agglutinin disease ( 125 ), membranoproliferative glomerulonephritis ( 126 ), antibody-mediated rejection of transplants ( 127 ), and, as mentioned above, C3 glomerulopathy ( 115 ). In adult patients, eculizumab is administered as 35 min intravenous infusion of 900 and 1,200 mg in PNH and aHUS, respectively, in weekly intervals in the first four weeks, followed by maintenance doses every 2 weeks ( 118 ).…”

Section: Terminal Complement Pathway-targeting Treatments Of Inflammamentioning

confidence: 99%

Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway

et al. 2020

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The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.

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“…Until now, marketing authorization for eculizumab has been obtained for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and refractory generalized myasthenia gravis (gMG) [ 1 , 5 , 6 ]. Noteworthy is the off-label use of eculizumab as a broad spectrum of other diseases (Table 1 ) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab

et al. 2019

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Eculizumab is the first drug approved for the treatment of complement-mediated diseases, and current dosage schedules result in large interindividual drug concentrations. This review provides insight into the pharmacokinetic and pharmacodynamic properties of eculizumab, both for reported on-label (paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis) and off-label (hematopoietic stem cell transplantation-associated thrombotic microangiopathy) indications. Furthermore, we discuss the potential of therapeutic drug monitoring to individualize treatment and reduce costs.

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Off-label use of the expensive orphan drug eculizumab in France 2009–2013 and the impact of literature: focus on the transplantation field

Abstract: Eculizumab started being notably used for off-label indications in France since the end of 2011, and this use increased until the end of the study. We found only low-level evidence concerning the off-label use of eculizumab in the transplantation field through the studied period.

Cited by 13 publications

References 60 publications

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data

Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway

Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab

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