Dysphagia and pharmacotherapy in older adults Wirth, Rainer; Dziewas, Rainer
Current opinion in clinical nutrition and metabolic care,
01/2019, Letnik:
22, Številka:
1
Journal Article
Sodium oligomannate (九期一
®
; GV-971) is a marine algae-derived oral oligosaccharide being developed by Shanghai Green Valley Pharmaceuticals for the treatment of Alzheimer’s disease (AD). Sodium ...oligomannate received its first approval in November 2019 in China for the treatment of mild to moderate AD to improve cognitive function. This article summarizes the milestones in the development of sodium oligomannate leading to this first approval for AD.
Intravenous (IV) and subcutaneous (SC) tocilizumab (RoActemra
®
), an IL-6 receptor antagonist, are approved (± methotrexate) in numerous countries throughout the world, for the treatment of adults ...with moderate to severe active rheumatoid arthritis (RA). Extensive clinical experience has firmly established the short- and long-term efficacy and safety of tocilizumab monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in adults with early-stage and longer-duration established RA. In the clinical trial and real-world settings, tocilizumab monotherapy or combination therapy provided rapid and sustained improvements in clinical and radiographic outcomes and health-related quality of life. The safety profile of tocilizumab is consistent over time and, in general, is consistent with that of other immunomodulatory agents. This narrative review, written from an EU perspective, summarizes the clinical use of IV and SC tocilizumab in RA. Given its low risk of immunogenicity, the flexibility of IV and SC administration and the convenience of the once-weekly, self-administered, SC regimen, tocilizumab provides an effective treatment for severe, active and progressive RA in adults not previously treated with methotrexate and an effective biologic first- or subsequent-line treatment for moderate to severe active RA in adults who have either responded inadequately to or were intolerant of previous therapy with ≥ 1 csDMARD or TNF inhibitor.
Aims
Measuring adherence to medication is complex due to the diversity of contexts in which medications are prescribed, dispensed and used. The Timelines‐Events‐Objectives‐Sources (TEOS) framework ...outlined a process to operationalize adherence. We aimed to develop practical recommendations for quantification of medication adherence using self‐report (SR), electronic monitoring (EM) and electronic healthcare databases (EHD) consistent with the TEOS framework for adherence operationalization.
Methods
An adherence methodology working group of the International Society for Medication Adherence (ESPACOMP) analysed implications of the process of medication adherence for all data sources and discussed considerations specific to SR, EM and EHD regarding the information available on the prescribing, dispensing, recommended and actual use timelines, the four events relevant for distinguishing the adherence phases, the study objectives commonly addressed with each type of data, and the potential sources of measurement error and quality criteria applicable.
Results
Four key implications for medication adherence measurement are common to all data sources: adherence is a comparison between two series of events (recommended and actual use); it refers to one or more specific medication(s); it applies to regular repeated events coinciding with known recommended dosing; and it requires separate measurement of the three adherence phases for a complete picture of patients' adherence. We propose recommendations deriving from these statements, and aspects to be considered in study design when measuring adherence with SR, EM and EHD using the TEOS framework.
Conclusion
The quality of medication adherence estimates is the result of several design choices that may optimize the data available.
Background
Moderate‐to‐severe atopic dermatitis (AD) often requires long-term management with systemic therapies.
Objective
Our objective was to report the safety and efficacy of dupilumab treatment ...up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w).
Methods
This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed.
Results
Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab’s safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was −91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was −68.74%. Efficacy was maintained in patients (
n
= 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen.
Conclusion
These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing.
Trial Registration ClinicalTrials.gov
NCT01949311.
Plain Language Summary
Atopic dermatitis is a chronic skin disease associated with inflamed skin and intense itching. People with moderate-to-severe atopic dermatitis often need long-term treatment, but many available treatments do not have demonstrated long-term safety data. In multiple clinical trials, dupilumab treatment resulted in significant improvements in signs and symptoms of atopic dermatitis. This study examined the safety and efficacy of up to 4 years of dupilumab treatment in adults with moderate-to-severe atopic dermatitis, and whether dupilumab continued to be effective in patients who switched from receiving treatment each week to treatment every other week. To address these questions, we collected data from adults who received 300 milligrams of dupilumab every week or every other week. In this study, safety findings were consistent with the known dupilumab safety profile. Patients' signs and symptoms were evaluated before and during treatment with evaluation tools including the Eczema Area and Severity Index (EASI), which indicates the extent and severity of disease, and the Pruritus Numerical Rating Scale (NRS), which indicates the intensity of itching. Reductions of 91% in EASI scores and 69% in Pruritus NRS scores showed that the improvement in signs and symptoms persisted for 204 weeks (almost 4 years) of treatment, and these effects were sustained following the switch from weekly treatment to the approved every other week treatment with dupilumab. The safety and efficacy data presented here support the use of dupilumab as a continuous, long-term treatment for up to 4 years for adults with moderate-to-severe atopic dermatitis.
Graphical abstract
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Video abstract:
What is the long-term safety and efficacy profile of dupilumab in adults with moderate-to-severeatopic dermatitis for up to 4 years? (MP4 102515 KB)
Introduction
Approximately a third of the population worldwide is chronically infected with
Toxoplasma gondii
. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis.
...Objective
The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main
Toxoplasma
manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and congenital toxoplasmosis.
Methods
PubMed, Cochrane Library, and Google Scholar databases were searched through August 1, 2016. Randomized, observational, prospective/retrospective, and cohort studies were eligible. Thirty-one studies were included with a total of 2975 patients. Of these, 13 were in congenital toxoplasmosis (
n
= 929), 11 in ocular toxoplasmosis (
n
= 1284), and seven in TE (
n
= 687). Across manifestations, adverse event (AE)-related treatment discontinuation and/or change in therapy involved ≤37% of patients and occurred in >55% of studies: 100% for ocular toxoplasmosis, 57.1% for TE, and 61.5% for congenital toxoplasmosis. The most commonly observed AEs were bone marrow suppression, dermatologic, and gastrointestinal (GI). The prevalence of bone marrow suppression-related AEs was ≤50% in congenital toxoplasmosis, ≤42.7% in TE, and ≤9.0% in ocular toxoplasmosis. The frequency of GI and dermatologic AEs were ≤100 and ≤11.1%, respectively, for ocular toxoplasmosis, ≤10.7 and ≤17.9% for TE, and ≤10.8 and ≤2.1% for congenital toxoplasmosis. Steven–Johnson syndrome was reported in two patients with ocular toxoplasmosis and one with TE.
Conclusion
The AE profile associated with pyrimethamine-based treatments differed by each manifestation of toxoplasmosis and within a given manifestation. Hematologic AEs occurred across all manifestations indicating the importance of monitoring the blood of patients administered pyrimethamine-based regimens.
Zanubrutinib: First Approval Syed, Yahiya Y.
Drugs (New York, N.Y.),
2020/1, Letnik:
80, Številka:
1
Journal Article
Recenzirano
Zanubrutinib (Brukinsa
®
), an orally-administered Bruton tyrosine kinase (BTK) inhibitor, is being developed by BeiGene for the treatment of B-cell malignancies. Zanubrutinib received accelerated ...approval in the USA on 14 November 2019 for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy, based on overall response rate (ORR) seen in phase II and I/II clinical trials. This article summarizes the milestones in the development of zanubrutinib leading to this first approval for the treatment of MCL.
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