Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders.

Rare diseases are infrequent, but together they affect up to 6-10 % of the world's population, mainly children. Patients require precise doses and strict adherence to avoid metabolic or cardiac failure in some cases, which cannot be addressed in a reliable way using pharmaceutical compounding. 3D printing (3DP) is a disruptive technology that allows the real-time personalization of the dose and the modulation of the dosage form to adapt the medicine to the therapeutic needs of each patient. 3D printed chewable medicines containing amino acids (citrulline, isoleucine, valine, and isoleucine and valine combinations) were prepared in a hospital setting, and the efficacy and acceptability were evaluated in comparison to conventional compounded medicines in six children. The inclusion of new flavours (lemon, vanilla and peach) to obtain more information on patient preferences and the implementation of a mobile app to obtain patient feedback in real-time was also used. The 3D printed medicines controlled amino acid levels within target levels as well as the conventional medicines. The deviation of citrulline levels was narrower and closer within the target concentration with the chewable formulations. According to participants' responses, the chewable formulations were well accepted and can improve adherence and quality of life. For the first time, 3DP enabled two actives to be combined in the same formulation, reducing the number of administrations. This study demonstrated the benefits of preparing 3D printed personalized treatments for children diagnosed with rare metabolic disorders using a novel technology in the real clinical practice over the current approach.

Therapeutic drug monitoring of anti-tumour necrosis factor-α agents in inflammatory bowel disease: Limits and improvements.

AIMS: Since the publication of the American Gastroenterological Association's recommendations in 2017, there have been no significant changes in the biological monitoring recommendations in inflammatory bowel disease. Possible limitations are the lack of evidence to recommend proactive therapeutic drug monitoring (pTDM) over reactive TDM (rTDM), and the limited information about individualized dosing methods. This article aims to review the TDM strategy updates and the use of individualized dosing methods. METHODS: For the analysis of the TDM strategies and individualized dosing method, a search was carried out in PubMed and Cochrane Central. In the TDM case, since August 2017. RESULTS: A total of 263 publications were found, but only 7 related to proactive TDM. Five of these publications directly compared pTDM vs rTDM and 2 were randomized clinical trials. Six studies found benefits of pTDM and 1 found no differences. Regarding the individualized dosing method, 229 distinct results were found. Population pharmacokinetics was the most widely used method to develop individual dosage models and to analyse the influence of factors on drug concentrations (albumin concentration, weight, presence of anti-drug antibodies etc). CONCLUSION: We have found no major changes in TDM strategies. There is a growing trend towards the use of pTDM because it has shown a longer duration of treatment response, lower rates of discontinuation and relapses. However, the available evidence is limited and of low quality. Despite the common use of population pharmacokinetic methods to analyse pharmacokinetic factors, they are not commonly used for personalized dosing.

Utilización rápida y segura de los autoinyectores de adrenalina. ¡Tenemos un problema / Rapid and safe use of adrenaline auto-injectors: We have a problem

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Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: First single-centre, prospective, crossover study in patients.

Maple syrup urine disease (MSUD) is a rare metabolic disorder with a worldwide prevalence of 1 in every 185,000 live births. However, certain populations display a significant overexpression of the disorder where incidence is reported to be 1 in every 52,541 new-borns. The first-line therapy for MSUD involves a strict dietary leucine restriction and oral supplementation of isoleucine and valine. The dose administered to patients requires strict tailoring according to age, weight and blood levels. In current clinical practice, however, practitioners still have to prepare extemporaneous formulations due to the lack of suitable oral treatments for MSUD. Herein, we evaluate the first time use of 3D printing in a hospital setting for the preparation of personalised therapies with the aim of improving safety and acceptability to isoleucine supplementation in paediatric patients suffering from MSUD. This investigation was a single-centre, prospective crossover experimental study. Four paediatric patients with MSUD (aged 3-16 years) were treated at the Clinic University Hospital in Santiago de Compostela, Spain which is a MSUD reference hospital in Europe. The primary objective was to evaluate isoleucine blood levels after six months of treatment with two types of formulations; conventional capsules prepared by manual compounding and personalised chewable formulations prepared by automated 3D printing. A secondary investigation was to evaluate patient acceptability of 3D printed formulations prepared with different flavours and colours. Isoleucine blood levels in patients were well controlled using both types of formulations, however, the 3D printed therapy showed mean levels closer to the target value and with less variability (200-400 µM). The 3D printed formulations were well accepted by patients regarding flavour and colour. The study demonstrates for the first time that 3D printing offers a feasible, rapid and automated approach to prepare oral tailored-dose therapies in a hospital setting. 3D printing has shown to be an effective manufacturing technology in producing chewable isoleucine printlets as a treatment of MSUD with good acceptability.

61.º Congreso de la SEFH. Nutrición parenteral libre de aminoácidos ramificados para el manejo urgente de una descompensación grave de la enfermedad del jarabe de arce / No disponible

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