Article
Clinical Neurology
Rosa Cortese, Marco Battaglini, Maria Pia Sormani, Ludovico Luchetti, Giordano Gentile, Maira Inderyas, Nektaria Alexandri, Nicola De Stefano
Summary: This study found that treatment with cladribine 3.5 mg/kg can significantly reduce grey matter (GM) atrophy in patients with relapsing multiple sclerosis (MS) compared to placebo, after a short period of pseudoatrophy. The study also suggests that GM damage is relevant in MS and may have important implications for physical and cognitive disability progression.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Gavin Giovannoni, Joela Mathews
Summary: Multiple sclerosis is a chronic neurodegenerative disease without a cure. The aim of therapy is to reduce relapse and disability progression. Immune reconstitution therapy (IRT) has become an important treatment option, and cladribine tablets are a selective and effective form of IRT for MS patients. They require fewer treatment courses and monitoring, improving patient adherence.
NEUROLOGY AND THERAPY
(2022)
Review
Clinical Neurology
Pierre Clavelou, Giovanni Castelnovo, Valerie Pourcher, Jerome De Seze, Patrick Vermersch, Ali-Frederic Ben-Amor, Carine Savarin, Gilles Defer
Summary: Cladribine tablets (CladT) is an effective oral therapy for RMS, suppressing disease activity with two short courses of treatment. It acts as an immune reconstitution therapy, reducing B lymphocytes and causing minimal impact on T lymphocytes. Precautions must be taken to manage infections and lymphopenia, while liver function should be monitored due to potential drug-induced liver injury. The risk of malignancy with CladT is similar to the general population and other RMS treatments.
NEUROLOGY AND THERAPY
(2023)
Article
Medicine, Research & Experimental
Daniela Rau, Beate Mueller, Susanne Uebler
Summary: This real-world study demonstrates the effect of cladribine tablets over 12 months on PROs of fatigue, physical function, treatment satisfaction, and work productivity. Results showed an alleviation of fatigue, stable physical function, and improvement in treatment satisfaction and work productivity.
ADVANCES IN THERAPY
(2023)
Article
Clinical Neurology
Martin Stangel, Veit Becker, Birte Elias-Hamp, Joachim Havla, Christoph Grothe, Refik Pul, Daniela Rau, Stephan Richter, Stephan Schmidt
Summary: The study evaluated various aspects of using oral cladribine tablets in practical clinical settings, including efficacy, risks, vaccinations, pregnancy, and monitoring requirements, with a consensus reached among a panel of neurologists experienced in multiple sclerosis therapy.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2021)
Article
Clinical Neurology
Bruno Brochet, Raymond Hupperts, Dawn Langdon, Alessandra Solari, Fredrik Piehl, Jeannette Lechner-Scott, Xavier Montalban, Krzysztof Selmaj, Martin Valis, Konrad Rejdak, Eva K. Havrdova, Francesco Patti, Nektaria Alexandri, Axel Nolting, Birgit Keller
Summary: This study aims to evaluate the effect of cladribine tablets on HRQoL in highly active multiple sclerosis patients. The study design is a two-year, pre-planned interim analysis focusing on treatment satisfaction, safety, and tolerability. The results showed high treatment satisfaction and good tolerability of cladribine tablets in highly active multiple sclerosis patients.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Clinical Neurology
Alessio Signori, Marta Ponzano, Nektaria Alexandri, Gavin Giovannoni, Maria Pia Sormani
Summary: This study demonstrates the application of the prevalence estimator of EDSS improvement in patients treated with cladribine tablets. The results show that cladribine tablets have a significantly higher prevalence of improvement compared to placebo at 2 years and 5 years. The prevalence estimator is found to be more powerful in assessing treatment effects over the long term compared to the cumulative incidence of improvement.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Ivan Adamec, Ivan Jovanovic, Magdalena Krbot Skoric, Mario Habek
Summary: This study reports on 6 patients with MS who experienced disease activity after alemtuzumab treatment, but remained relapse-free and stable after subsequent treatment with cladribine for up to 2 years. None of the patients experienced infections or malignancies during the follow-up period.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Jihad Inshasi, Samar Farouk, Ahmed Shatila, Ali Hassan, Miklos Szolics, Mona Thakre, Deeb Kayed, Derk Krieger, Abubaker Almadani, Taoufik Alsaadi, Beatrice Benedetti, Victoria Mifsud, Anu Jacob, Shatha Sayegh, Amir Boshra, Raed Alroughani
Summary: This study evaluated treatment satisfaction with cladribine tablets for relapsing multiple sclerosis in the Arabian Gulf, and found high levels of overall satisfaction, ease of use, tolerability, and effectiveness among patients.
NEUROLOGY AND THERAPY
(2023)
Article
Clinical Neurology
Per Soelberg Sorensen, Luigi Pontieri, Hanna Joensen, Alex Heick, Peter Vestergaard Rasmussen, Jakob Schafer, Rikke Ratzer, Caroline Ellinore Pihl, Finn Sellebjerg, Melinda Magyari
Summary: Cladribine is an effective treatment for relapsing multiple sclerosis by reducing lymphocyte levels, especially B-cells. This real-world study in Denmark examined the treatment patterns and outcomes of cladribine therapy, finding it to be safe and effective in line with previous clinical trials.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Review
Clinical Neurology
Jihad S. Inshasi, Sarmed Alfahad, Taoufik Alsaadi, Ali Hassan, Tayseer Zein, Victoria Ann Mifsud, Suzan Ibrahim Nouri, Mustafa Shakra, Ahmed Osman Shatila, Miklos Szolics, Mona Thakre, Ajit Kumar, Amir Boshra
Summary: Immune reconstitution therapies in patients with RRMS can prolong the time free from relapses, while cladribine tablets have been shown to be effective and well tolerated in active MS patients. Moreover, there is currently no evidence of adverse interactions between cladribine tablets and COVID-19 infection or vaccination.
NEUROLOGY AND THERAPY
(2021)
Article
Clinical Neurology
Mirna Matni, Bassem Yamout, Salam Koussa, Chaker Khamis, Lora Fleifel, Shahdak Sharifi, Omneya Mohamed
Summary: Cladribine tablets are a cost-effective and budget-saving treatment option for HDA-RMS patients in Lebanon from the perspective of the NSSF. Cost-utility analysis shows that cladribine tablets have economic advantages and better quality of life years compared to other comparator drugs. Budget impact analysis also shows that the introduction of cladribine tablets can result in savings of 5.0% to 21.5% in the overall budget over a period of five years.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Neurosciences
Lucia Moiola, Agostino Riva, Ferdinando Nicoletti, Antonio Uccelli, Marco Salvetti, Luca Battistini, Roberto Furlan
Summary: The COVID-19 pandemic and mass vaccination campaigns have raised concerns about vulnerable patients, particularly those with Multiple Sclerosis (MS) receiving cladribine tablets. This study analyzed existing literature and vaccination experiences to determine the safety and efficacy of administering vaccines to cladribine-treated patients. The findings suggest that vaccination timing can be flexible and that vaccination in these patients should be safe and effective.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Clinical Neurology
Mario Habek, Jelena Drulovic, Gregor Brecl Jakob, Ivan Barbov, Ljiljana Radulovic, Cecilia Rajda, Konrad Rejdak, Peter Turcani
Summary: Based on the CLARITY study, cladribine tablets were approved for use in the EU in 2017 as a high-efficacy therapy for highly active relapsing-remitting MS. Limited evidence exists on managing patients beyond 4 years after cladribine treatment. Postapproval data show that two cycles of cladribine effectively control disease activity in the long term. Retreatment with cladribine may benefit patients with minimal or moderate disease activity, while switching to another high-efficacy treatment is recommended for patients with significant disease activity or progression.
NEUROLOGY AND THERAPY
(2023)
Article
Clinical Neurology
Yan Song, Yan Wang, Schiffon L. Wong, Danni Yang, Manasvi Sundar, Namita Tundia
Summary: This study aimed to assess the real-world treatment patterns and effectiveness of cladribine tablets (CladT) in relapsing forms of multiple sclerosis (RMS). The results showed that patients treated with CladT had low switch rates, reduced relapse rate, disease severity, corticosteroid use, and healthcare resource utilization.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Pharmacology & Pharmacy
Robert Hermann, Jeffrey S. Litwin, Lena E. Friberg, Fernando Dangond, Alain Munafo
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2019)
Editorial Material
Pharmacology & Pharmacy
Hartmut Derendorf, Oliver von Richter, Robert Hermann, Amin Rostami-Hodjegan
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2019)
Article
Pharmacology & Pharmacy
Diego Vera-Yunca, Pascal Girard, Zinnia P. Parra-Guillen, Alain Munafo, Inaki F. Troconiz, Nadia Terranova
Article
Pharmacology & Pharmacy
Robert Hermann, Kristina Gundlach, Dan Seiler
Summary: This study revealed that when three drugs (ramipril, amlodipine, atorvastatin) were coadministered, amlodipine had minimal impact on the pharmacokinetic parameters of atorvastatin and itself, but had a significant effect on ramipril and ramiprilat, possibly due to slowing intestinal motility and enhancing the bioavailability of ramipril.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2021)
Article
Pharmacology & Pharmacy
Diego Vera-Yunca, Zinnia P. Parra-Guillen, Pascal Girard, Inaki F. Troconiz, Nadia Terranova
Summary: A semi-mechanistic TGI and OS model has been developed in a large population of mCRC patients, with findings suggesting that KRAS wild-type status and right-sided primary lesions are related to drug efficacy and resistance to cetuximab. Early appearance of new lesions, large tumor size at baseline, and tumor heterogeneity are the main predictors of overall survival.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Robert Hermann, Peter Krajcsi, Markus Fluck, Annick Seithel-Keuth, Afrim Bytyqi, Andrew Galazka, Alain Munafo
Summary: Cladribine is a drug used to treat patients with relapsing multiple sclerosis, which is phosphorylated in target cells to its active adenosine triphosphate form. The distribution of cladribine across biological membranes is facilitated by several uptake and efflux transporters, and it plays a role in intestinal absorption, distribution throughout the body, and intracellular uptake.
CLINICAL PHARMACOKINETICS
(2021)
Article
Pharmacology & Pharmacy
Emeric Sibieude, Akash Khandelwal, Jan S. Hesthaven, Pascal Girard, Nadia Terranova
Summary: This study demonstrates the application of supervised learning algorithms in pharmacometry population modeling, comparing various classical methods and machine learning methods, proving the potential advantage of machine learning methods in identifying relationships between parameters and covariates.
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
(2021)
Review
Pharmacology & Pharmacy
Robert Hermann, Peter Krajcsi, Markus Fluck, Annick Seithel-Keuth, Afrim Bytyqi, Andrew Galazka, Alain Munafo
Summary: Cladribine is a nucleoside analog used to treat relapsing multiple sclerosis, with its absorption and distribution in the body mediated by various nucleoside transporters. Ensuring optimal therapy for patients with cladribine involves being mindful of medications and dietary components that may affect its absorption and cellular uptake.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Emeric Sibieude, Akash Khandelwal, Pascal Girard, Jan S. Hesthaven, Nadia Terranova
Summary: This study discusses the benefits of utilizing supervised machine learning algorithms in optimizing the development of population pharmacometric models, demonstrating that machine learning can greatly enhance the efficiency of model selection, particularly in cases of large datasets or complex models. Machine learning approaches provide fast and accurate model selection, complementing traditional pharmacometric methods.
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
(2022)
Article
Pharmacology & Pharmacy
Sreetama Basu, Alain Munafo, Ali-Frederic Ben-Amor, Sanjeev Roy, Pascal Girard, Nadia Terranova
Summary: This study used machine learning to predict disease activity status in patients with multiple sclerosis (MS) and identified the most predictive covariates. The findings can help identify disease activity early and prompt proper treatment interventions.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2022)
Editorial Material
Pharmacology & Pharmacy
Jackson Burton, Bilal Abuasal, Sagar Bachhav, Jamie Connarn, Josh Cosman, Neeraj Gupta, Jing Jing, Sarah Kim, Tao Long, Nadia Terranova, Karthik Venkatakrishnan, Jian Wang, Qi Liu
Summary: Significant opportunities are emerging for clinical pharmacology to improve drug development through the use of rapidly evolving innovations in biomedical research. Current and upcoming innovations in the field can be classified into three major categories: new therapeutic modalities, expanding data types, and new analytical tools. The Pharmacometrics and Pharmacokinetics (PMK) community within the American Society for Clinical Pharmacology and Therapeutics (ASCPT) aims to facilitate collaboration, communication, and scientific advancement in these areas, addressing both the opportunities and challenges they present. This perspective seeks to encourage scientific collaboration across a wide range of ASCPT networks and communities, focusing on opportunities and challenges in the field of clinical pharmacology and beyond.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Medicine, Research & Experimental
Robert Hermann, Amin Rostami-Hodjegan, Ping Zhao, Isabelle Ragueneau-Majlessi
Summary: Smoking drug interaction studies play an important role in clinical investigation, but they are often neglected and lack methodological standards. A systematic review of published literature on smoking pharmacokinetic interaction studies revealed that the methods used are heterogeneous and fall short of established standards. The deficiencies include incomplete description of study populations, lack of confirmation of smoker and nonsmoker characteristics, under-representation of female subjects, small sample sizes, lack of statistical planning, and inadequate control of external factors. Efforts are needed to address these quality issues for actionable decisions on dose optimization in smokers.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Nadia Terranova, Didier Renard, Mohamed H. Shahin, Sujatha Menon, Youfang Cao, Cornelis E. C. A. Hop, Sean Hayes, Kumpal Madrasi, Sven Stodtmann, Thomas Tensfeldt, Pavan Vaddady, Nicholas Ellinwood, James Lu
Summary: Recent breakthroughs in AI and ML have opened up new possibilities in various scientific domains, particularly in model-informed drug discovery and development. The IQ Consortium's AI/ML working group aims to promote the acceptance and adoption of these advanced algorithms across the scientific community and regulatory agencies. This white paper, based on insights from workshops attended by key stakeholders, covers a range of applications and offers best practices for the effective and responsible use of AI in quantitative modeling.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Ana-Marija Milenkovic-Grisic, Nadia Terranova, Diane R. Mould, Yulia Vugmeyster, Thomas Mrowiec, Andreas Machl, Pascal Girard, Karthik Venkatakrishnan, Akash Khandelwal
Summary: The study used population pharmacokinetic-pharmacodynamic modeling, as well as pharmacometric and machine-learning approaches, to analyze tumor dynamics in patients receiving bintrafusp alfa or pembrolizumab. The results showed that different covariates and drug exposure had varying effects on tumor dynamics, and identified factors related to hyperprogression. However, these factors were not considered clinically relevant in terms of their impact on tumor size.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Oncology
Nadia Terranova, Mendel Jansen, Martin Falk, Bart S. Hendriks
Summary: Berzosertib is a first-in-class inhibitor being developed in combination with chemotherapy for the treatment of advanced cancers. Population PK analysis showed that concentrations of berzosertib exceeded p-Chk1 IC50 at recommended phase II doses when combined with carboplatin, cisplatin, and gemcitabine, indicating its potential efficacy in these combinations without significant PK interactions.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)