Publications by authors named "Andrew Galazka"
Multiple sclerosis (MS) is a chronic, progressive, inflammatory disorder of the central nervous system. Relapsing-remitting MS (RRMS), the most common form of the disease, is characterized by transient neurological dysfunction with concurrent accumulation of disability. Over the past three decades, disease-modifying therapies (DMTs) capable of reducing the frequency of relapses and slowing disability worsening have been studied and approved for use in patients with RRMS.
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- The article summarizes findings from the CLARITY and CLARITY Extension studies on the effectiveness of cladribine tablets in treating relapsing forms of multiple sclerosis (MS).
- The studies showed that individuals taking cladribine tablets had a significantly lower risk of experiencing relapses compared to those taking a placebo, with some participants continuing to experience benefits for up to three years after initial treatment.
- Researchers suggest that the recommended two-year dosing of cladribine tablets may provide lasting relief from relapses for up to five years in MS patients.
What Is This Summary About?: This article summarizes the findings from a previously published article in . Cladribine tablets are an oral treatment for relapsing multiple sclerosis (shortened to MS), that are given for 4 periods of 4 to 5 days over 2 years (for a total of 20 days). In this analysis, researchers looked at the effects of taking either cladribine tablets or placebo (dummy pills) in a group of people with MS who had more active MS inflammation and had participated in a clinical study (called the CLARITY study).
View Article and Find Full Text PDFCladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or >50 years) on lymphopenia following CladT 3.
View Article and Find Full Text PDFCladribine is a nucleoside analog that is phosphorylated in its target cells (B and T-lymphocytes) to its active triphosphate form (2-chlorodeoxyadenosine triphosphate). Cladribine tablets 10 mg (Mavenclad), administered for up to 10 days per year in 2 consecutive years (3.5-mg/kg cumulative dose over 2 years), are used to treat patients with relapsing multiple sclerosis.
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- Cladribine is a nucleoside analog used to treat relapsing multiple sclerosis, administered as tablets (10 mg) for 10 days each year over two years, resulting in a total dose of 3.5 mg/kg.
- The drug must be activated in the body to its triphosphate form, with its distribution influenced by various transporters, including specific nucleoside transporters (ENT and CNT) and the breast cancer resistance protein.
- Evidence suggests that cladribine's transport across membranes mainly involves certain transporters, while no significant role is found for common solute carrier transporters, indicating low likelihood for cladribine to inhibit these transporters in vivo.
Article Synopsis
- The CLARITY study demonstrated that cladribine tablets (3.5 mg/kg) significantly decrease the annualised relapse rate (ARR) in patients with relapsing-remitting multiple sclerosis compared to a placebo, with lasting effects observed in the follow-up extension period without additional treatment.
- Over two years, patients on cladribine experienced fewer relapses and severe relapses, with statistically significant results showing improvements at multiple checkpoints.
- The findings confirm that cladribine tablets provide durable effectiveness in managing the frequency and severity of relapses in relapsing-remitting multiple sclerosis patients.
COVID-19 in patients with multiple sclerosis treated with cladribine tablets: An update.
Mult Scler Relat Disord
June 2021
Background: We previously summarized outcomes for 46 cladribine tablets (CladT)-treated patients with multiple sclerosis (MS) and confirmed or suspected COVID-19, as reported to the Merck KGaA Global Patient Safety Database. This report updates on these findings, to 15 January 2021, for a total of 272 reported cases of COVID-19 among CladT recipients.
Methods: Case definitions: confirmed (COVID-19 diagnostic test was positive); suspected (no confirmatory test performed/reported).
Background: In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE).
View Article and Find Full Text PDFBackground: In the Phase 3, 96-week ORACLE-MS study, cladribine 10 mg tablets (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly reduced the rate of conversion to clinically definite multiple sclerosis (CDMS) per the Poser criteria (henceforth referred to as CDMS), multiple sclerosis (MS) per the 2005 McDonald criteria, and the number of new or persisting T1 gadolinium-enhancing (Gd+), new or enlarging T2, and combined unique active (CUA) lesions versus placebo in participants with a first clinical demyelinating event (FCDE).
View Article and Find Full Text PDFBackground: Relapsing-remitting multiple sclerosis (RRMS) patients with high disease activity (HDA) experience more severe disease than those without HDA. This analysis describes the efficacy of cladribine tablets 3.5 mg/kg in HDA patient subgroups that were either treated with disease-modifying drugs (DMDs) prior to study entry or were treatment naïve.
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- * The treatment involves two oral cycles each year for two years, potentially eliminating the need for further doses in the following years, making it a convenient option for patients with relapsing forms of MS.
- * Clinical studies, including the significant phase III CLARITY trial, demonstrated the efficacy and safety of cladribine tablets, leading to global approval for the treatment of various types of relapsing MS.
Introduction: Although use of contraception was pre-specified during cladribine clinical trials for multiple sclerosis, some pregnancies did occur.
Objective: This analysis reports on pregnancy outcomes in the cladribine clinical development program.
Methods: Pregnancy outcomes in female patients (direct pregnancies) and those arising from partner pregnancies (i.
Article Synopsis
- Immune reconstitution therapies (IRT) for multiple sclerosis, like cladribine tablets, aim to reset the immune system, allowing for treatment-free periods after initial therapy.
- The study analyzed long-term lymphocyte count changes from pooled data of the CLARITY studies and the PREMIERE registry, focusing on patients who received cladribine versus those on placebo.
- Results indicated that cladribine treatment led to temporary reductions in B and T lymphocytes, but these counts returned to normal ranges within 1-2 years after treatment cessation.
Background: Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously.
Objective: Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets.
Purpose: We applied Multi-Criteria Decision Analysis (MCDA) methods in a structured benefit-risk assessment of cladribine and newer approved disease-modifying drugs (DMDs) for patients with relapsing-remitting multiple sclerosis (RRMS).
Methods: Decision conferencing with clinical neurologists as decision makers was used to create an MCDA model that incorporated available evidence on DMDs for RRMS and clinical judgments about the relevance of the evidence. Benefit-risk assessments were conducted for DMDs in both patients with RRMS and patients with RRMS with high disease activity (HDA; defined as ≥2 relapses in the previous year).