Safety of Rituximab biosimilar (Riximyo®) following a single switch from the reference product in patients with Non-Hodgkin's lymphoma: a retrospective study.

Unlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for "switching therapy" with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes.

Patient beliefs associated with medication hesitancy in palliative care: A systematic review using the theory of planned behavior.

CONTEXT: The demand of palliative care is increasing due to the aging population and treatment hesitancy or intentional avoidance compromises symptom management. OBJECTIVES: To identify patient beliefs associated with medication hesitancy by using the theory of planned behavior (TPB) namely, attitudes, subjective norms, behavioral intention, and perceived behavioral control associated with medication hesitancy or intentional noncompliance by avoidance. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to conduct a systematic literature search involving the CINAHL, Embase, MEDLINE, and PsycINFO databases from inception until March 2022. Hand-searched articles from reference lists and gray literature were included. Thematic analysis was conducted on qualitative data and triangulated with quantitative data. RESULTS: About 554 articles were retrieved from the literature search and 17 articles were included based on the eligibility criteria. Three subthemes that were identified under TPB constructs were attitude: negative attitude toward medications, passive attitude toward illness and inaccurate information about disease or medication; one subtheme was identified under subjective norms: perceived negative opinions from others; and one subtheme was identified under perceived behavioral control: perception of manageable symptoms. Quantitative data provided triangulation of qualitative findings related to fear of addiction and side effects, feelings of hopelessness, unclear direction and information, social stigma, endurable symptoms, and illness as determinants for medication avoidance. SIGNIFICANCE OF RESULTS: This systematic review highlighted some patient beliefs related to medication hesitancy or avoidance. Clinicians should take patient beliefs and concerns into consideration when creating treatment regimens for people receiving palliative care to optimize medication adherence and the quality of care.

Pharmacological Characterization and Investigation of N-Terminal Loop Amino Acids of Adrenomedullin 2 That Are Important for Receptor Activation.

Adrenomedullin 2 (AM2) is a peptide hormone with potent effects in the cardiovascular system. The N-terminal disulfide loop of AM2 is thought to be important for interacting with its receptors to initiate a signaling response. However, the relative contribution of each amino acid within this region is currently unknown. Thus, the region was investigated using an alanine scanning approach. Two AM2 peptides (AM2-47 and AM2-40) were directly compared at the CGRP, AM1, and AM2 receptors in transfected Cos7 cells and found to have equivalent activity. Analogues of AM2-40 were then synthesized, substituting each individual amino acid within the disulfide loop with alanine. The ability of these analogues to stimulate a cAMP response was evaluated at the CGRP, AM1, and AM2 receptors. AM2-40 L12A and T14A were less able to elicit cAMP responses through all tested receptors. In contrast, AM2-40 G13A was slightly more potent than the unmodified peptide at all tested receptors. Thus, it appears that residues within the disulfide loop region play differential roles in the ability of AM2 to stimulate cAMP production. The data provide the first structure-function investigation of AM2 agonism.