Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. Objectives The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps. Methods A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies. Results The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups. Conclusions There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching

Mail [The facts about low dose methotrexate]

Comment on: Cytotoxic chemotherapy administration in the community: A case study. [Aust Nurs Midwifery J. 2015] We are writing in response to the article Cytotoxic Chemotherapy Administration in the Community: A Case Study which was published in the December 2015 edition of the ANMJ. It was disappointing to read this misleading article about a patient with rheumatoid arthritis (RA) whose treatment included intramuscular low dose methotrexate (LDM) and the need for full cytotoxic PPE

Resonance raman-spectroscopy of hemoglobin in intact-cells: A probe of oxygen-uptake by erythrocytes in rheumatoid arthritis

Resonance Raman spectra from intact viable erythrocytes can be used to study oxygen uptake in solution. In addition to changes in the oxidation state marker (v4), other bands due to the porphyrin ring (v3) and vinyl modes indicate subtle changes at oxygen pressures close to where the T/R change occurs. A comparison of whole cell and lysate spectra indicates a partial denaturation of hemoglobin on lysis. A simple smear technique is used to measure spectra from rheumatoid and normal blood. Results indicate a faster but less complete uptake of oxygen in cells from patients with rheumatoid arthritis than is the case in normal cell populations

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

Background: The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. Objectives: The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps. Methods: A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies. Results: The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups. Conclusions: There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.Administrative and medical writing support was provided by Ms Donna Bartlett (Allori Pty Ltd, Australia) and Dr. Anja Becher (Sydney, Australia), and was funded through Medicines Australia with specific support from the Australian affiliates of AbbVie, Amgen, Eli Lilly, Janssen, Novo Nordisk, Roche and Sanofi

A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic Disease Modifying Anti-Rheumatic Drugs for the Treatment of Inflammatory Arthritis in Patients with a History of Malignancy

Purpose of Review: Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. Recent Findings: Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of real world data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Summary: Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients