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

Data quality predicts care quality: findings from a national clinical audit

Background: Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance. Methods: The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment. Results: Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001). Conclusions: We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator

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

The evidence for biologic immunotherapy in Sarcoidosis: A systematic review

BackgroundSarcoidosis is a chronic inflammatory disease with a myriad of clinical manifestations. Treatment involves immunosuppression with corticosteroids or steroid-sparing agents. A proportion of patients does not respond to or are intolerant to therapy. Targeted immunotherapy with biologic agents has emerged as a novel approach with plausible mechanistic reasons to warrant study. AimsThe aim of this review was to evaluate the evidence for the efficacy of biological therapy in sarcoidosis.Methods We conducted a systematic literature review and meta-analysis of all published randomised-controlled trials (RCT) evaluating biological therapy in sarcoidosis, using MEDLINE and Embase databases, through to September 2017. The search terms included sarcoidosis, infliximab, adalimumab, etanercept, golimumab, certolizumab, rituximab, abatacept, tocilizumab, anakinra, ustekinumab, secukinumab. Only articles reporting RCTs were selected. Improvements in respiratory disease were assessed by changes in forced vital capacity (FVC) by weighted mean difference (WMD). There were insufficient data on outcome measures in other organ systems to comparatively assess efficacy.Results The search identified 2,324 studies of which only 5 provided relevant and original data. This comprised a total of 364 patients, evaluating pulmonary, cutaneous and ocular sarcoidosis. One study in pulmonary disease and one study in cutaneous disease demonstrated improvements in the primary outcome. In pulmonary disease, meta-analysis of the treatment effect of anti-TNF therapy versus placebo on FVC revealed a WMD of 1.69 per cent (95 per cent confidence interval, 1.44–1.94). ConclusionThere are insufficient data to suggest the long-term efficacy of anti-TNFα inhibitors in the treatment of sarcoidosis. This may be due to heterogeneity, small sample sizes and the lack of consistent reporting of outcome measures

Generation of human parallel chimeric antigen receptor (pCAR) T cells to achieve synergistic T cell co-stimulation

Dual co-stimulation may be harnessed using parallel chimeric antigen receptors (pCARs) in which two distinct co-stimulatory units are adjacently localized on the plasma membrane. This protocol summarizes construct design, human T cell isolation, retroviral transduction, tissue culture expansion, and preclinical testing of pCAR T cells, exemplified by receptors that co-target avb6 integrin and ErbB dimers. For complete details on the use and execution of this protocol, please refer to Muliaditan et al. (2021)

Electronic screening for mental illness in patients with psoriasis

In this cross sectional study from a large UK centre, screening for mental illness in individuals with psoriasis has demonstrated a high burden of depression and anxiety. 85% of the cohort report that their psoriasis had affected their quality of life. Quality of life scores correlate with depression scores, emphasing the importance of managing individual's mental health alongside their psoriasis to improve overall quality of life

Non-linear operations in quantum information theory

Quantum information theory is used to analize various non-linear operations on quantum states. The universal disentanglement machine is shown to be impossible, and partial (negative) results are obtained in the state-dependent case. The efficiency of the transformation of non-orthogonal states into orthogonal ones is discussed.Comment: 11 pages, LaTeX, 3 figures on separate page

Occupational impacts of early inflammatory arthritis : results from the National Early Inflammatory Arthritis Audit

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