Patient perception of treatment efficacy, disability and health satisfaction

Abstract published in Rheumatology, Volume 55 (Suppl 1), April 2016, page i123

New biologic agents and biosimilars developed for rheumatoid arthritis

The pathogenesis of rheumatoid arthritis (RA) is characterised by interactions between several types of immune cells, which are associated with the release of multiple inflammatory cytokines. Recently, numerous biologic treatments targeting classes of immune cells, cytokines or intra-cellular pathways of pro-inflammatory signals have been developed. Some of them are currently under research as potential therapeutic options for RA patients. This chapter reviews the available evidence regarding the safety and efficacy of new biologic agents targeting B cells, proinflammatory interleukins (IL), T helper 17 (Th17) pathway and intracellular enzymes. This chapter reviews the most relevant randomised controlled trials (RCTs) which have proven the efficacy of different biologic agents and small molecule inhibitors in controlling the inflammation associated with RA. The management of RA remains a dynamic and evolving field. The development of less expensive ‘biosimilar’ drugs, analogous to existing licensed biologic therapies, is an emerging area of research that deserves particular attention

Tumour necrosis factor inhibitors used in the treatment of rheumatoid arthritis: Evidence of safety, efficacy and health implication

Rheumatoid arthritis (RA) is a systemic autoimmune condition characterised by inflammation and destruction of synovial joints. The pathogenesis of inflammation is underpinned by interaction and activation of immune cells, which release inflammatory cytokines such as tumour necrosis factor (TNF) and interleukins. These mechanisms of disease pathogenesis were targeted by specific drugs in the form of monoclonal antibodies (mAb) or soluble receptors. The advent of biological disease modifying therapies (bDMARDs) has revolutionised the management of RA. These agents dramatically reduce synovial inflammation, halt the progression of radiographic joint damage, and improve functional ability and health related quality of life outcomes. This has a positive impact on the socioeconomic burden of RA. This chapter reviews the pathogenesis of RA and evidence behind the use of TNF inhibitors licensed for RA treatment. We focus on clinical efficacy, safety profile and cost-effectiveness of infliximab, etanercept, adalimumab, certolizumab, golimumab. Additionally, we discuss national and international recommendations for the clinical use of TNF inhibitors, with further consideration of the financial implications. Examples of clinical randomised controlled trials (RCTs), which have proven the efficacy of different TNF inhibitors in RA are also included in this chapter. The use of TNF inhibitor biosimilars will be discussed in chapter 11

Biologic treatments (other than anti-TNF therapy) licensed for use in rheumatoid arthritis

Despite the huge progress made by the use of tumour necrosis factor (TNF) inhibitors in the treatment of rheumatoid arthritis (RA), there was still an unmet need for discovering and implementing new biologic therapies for RA patients who lost response or had side-effects to TNF inhibitors. The advances in molecular biology and understanding of the complex pathogenesis of RA enabled the identification of other pivotal molecules, whose blockage was associated with clinical benefits in RA. This chapter reviews the clinical efficacy, safety profile and cost-effectiveness of several biologic agents licensed for use in RA patients, which target different interleukins (IL), such as IL1 (anakinra) and IL6 (tocilizumab), or are associated with B cell depletion (rituximab), T cell co-stimulatory blockage (abatacept) and small molecule inhibition (tofacitinib). In addition, we discuss the national and international guidelines for use of these biologic agents in relation to the use of TNF inhibitors in patients with moderatesevere RA, providing examples of switching between various biologic therapies

Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.

Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review

To date, no consensus exists among stakeholders about the safety of switching between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real-world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open-label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect

The Novella Project: developing a sustainable supply chain for Allanblackia oil

The Novella Project, a collaboration between a commercial company (Unilever), an international Non-Governmental Organization (NGO) (SNV Netherlands Development Organisation), local NGOs, local businesses, collectors, transporters and processors, aims at developing a strong, effective and sustainable international supply chain for Allanblackia oil. Success of the chain will increase when more local farmers and collectors will find the additional incomes attractive enough to get involved. A strong chain, with clear business opportunities, will encourage the local communities not only to protect the Allanblackia trees, but also to offer similar protection to all trees in the forest, thereby contributing to explicit sustainable forest management and maintenance of biodiversity. Unilever has already shown commitment to developing a sustainable supply chain by offering to support local communities to plant more Allanblackia trees on their farms and closer to the communities. The project’s choice to focus on the empowerment of women is strategic as their participation can lead to improved livelihoods and stability of family incomes, which are important objectives of the project. For the commercial partners, including Unilever, a strong market chain is expected to translate into an acceptable return on investment. The chain is in its development stage and is confronted with a number of challenges. The collection of seeds from wild-growing trees in dense tropical forest and low tree density in village areas lead to high transaction costs for collection of the seeds along the chain. Also being a new market chain intense information, education and communication is required over a long period throughout the project areas to transfer knowledge, skills and project information to current and potential supplychain actors. In the complex partnership different interests risk to compete with common defined objectives. There is the challenge of increasing involvement of local businesses and investments in the key areas of the chain. SNV has a crucial responsibility in addressing these challenges by supporting different partners involved in the project

Characterization of Electronic Health Record Use Outside Scheduled Clinic Hours Among Primary Care Pediatricians: Retrospective Descriptive Task Analysis of Electronic Health Record Access Log Data

BackgroundMany of the benefits of electronic health records (EHRs) have not been achieved at expected levels because of a variety of unintended negative consequences such as documentation burden. Previous studies have characterized EHR use during and outside work hours, with many reporting that physicians spend considerable time on documentation-related tasks. These studies characterized EHR use during and outside work hours using clock time versus actual physician clinic schedules to define the outside work time. ObjectiveThis study aimed to characterize EHR work outside scheduled clinic hours among primary care pediatricians using a retrospective descriptive task analysis of EHR access log data and actual physician clinic schedules to define work time. MethodsWe conducted a retrospective, exploratory, descriptive task analysis of EHR access log data from primary care pediatricians in September 2019 at a large Midwestern pediatric health center to quantify and identify actions completed outside scheduled clinic hours. Mixed-effects statistical modeling was used to investigate the effects of age, sex, clinical full-time equivalent status, and EHR work during scheduled clinic hours on the use of EHRs outside scheduled clinic hours. ResultsPrimary care pediatricians (n=56) in this study generated 1,523,872 access log data points (across 1069 physician workdays) and spent an average of 4.4 (SD 2.0) hours and 0.8 (SD 0.8) hours per physician per workday engaged in EHRs during and outside scheduled clinic hours, respectively. Approximately three-quarters of the time working in EHR during or outside scheduled clinic hours was spent reviewing data and reports. Mixed-effects regression revealed no associations of age, sex, or clinical full-time equivalent status with EHR use during or outside scheduled clinic hours. ConclusionsFor every hour primary care pediatricians spent engaged with the EHR during scheduled clinic hours, they spent approximately 10 minutes interacting with the EHR outside scheduled clinic hours. Most of their time (during and outside scheduled clinic hours) was spent reviewing data, records, and other information in EHR