Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a review

Israa Al-Shakarchi, Nicola J Gullick, David L ScottDepartment of Rheumatology, Kings College Hospital, London, UKAbstract: Rheumatoid arthritis (RA) remains a major clinical problem with many patients having continuing systemic inflammatory disease resulting in progressive erosive damage and high levels of disability. A range of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 are involved in RA pathogenesis; these cytokines can be specifically inhibited by biological agents. Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor monoclonal antibody, administered monthly by intravenous infusion that prevents IL-6 signal transduction. There is strong evidence that it is both clinically efficacious and cost-effective. There have been several key clinical trials evaluating the safety and efficacy of TCZ in RA patients. We review five Phase II trials and seven Phase III trials enrolling a total of 626 and 5268 RA patients respectively. The American College of Rheumatology (ACR) response criteria were used as the primary or secondary outcome measure in all trials. Overall these trials demonstrated that TCZ was effective in the treatment of RA in a number of patient groups, including those with an inadequate response to methotrexate (MTX) or TNF inhibition. TCZ use, both as monotherapy and in combination with MTX, improved the signs and symptoms of RA within several weeks of commencing treatment. Additionally, TCZ was shown to reduce radiological disease progression and improve physical function, both as monotherapy and in combination with MTX. A 5-year extension study demonstrated that TCZ sustained good long-term efficacy and safety profiles. TCZ was generally well tolerated. Although its use increased the risk of an adverse event, these were usually mild to moderate in severity and treatment did not increase the risk of a serious adverse event in comparison to controls. Due to moderate increases in serum levels of total cholesterol, triglycerides, high-density lipoproteins and serum transaminases seen in those patients treated with TCZ, as well as severe neutropenia in some, regular blood monitoring of full blood count, liver function and lipids is recommended. Given its clinical efficacy in the treatment of RA, TCZ may be beneficial in the treatment of other autoimmune diseases where IL-6 plays a role in the inflammatory cascade.Keywords: tocilizumab, rheumatoid arthritis, review, IL-

Cardiovascular disease in homeless versus housed individuals: a systematic review of observational and interventional studies

Objectives: To identify: (i) risk of cardiovascular disease (CVD) in homeless versus housed individuals and (ii) interventions for CVD in homeless populations. Methods: We conducted a systematic literature review in EMBASE until December 2018 using a search strategy for observational and interventional studies without restriction regarding languages or countries. Meta-analyses were conducted, where appropriate and possible. Outcome measures were all-cause and CVD mortality, and morbidity. Results: Our search identified 17 articles (6 case-control, 11 cohort) concerning risk of CVD and none regarding specific interventions. Nine were included to perform a meta-analysis. The majority (13/17, 76.4%) were high quality and all were based in Europe or North America, including 765 459 individuals, of whom 32 721 were homeless. 12/17 studies were pre-2011. Homeless individuals were more likely to have CVD than nonhomeless individuals (pooled OR 2.96; 95% CI 2.80 to 3.13; p<0.0001; heterogeneity p<0.0001; I 2 =99.1%) and had increased CVD mortality (age-standardised mortality ratio range: 2.6–6.4). Compared with nonhomeless individuals, hypertension was more likely in homeless people (pooled OR 1.38–1.75, p=0.0070; heterogeneity p=0.935; I 2 =0.0%). Conclusions: Homeless people have an approximately three times greater risk of CVD and an increased CVD mortality. However, there are no studies of specific pathways/interventions for CVD in this population. Future research should consider design and evaluation of tailored interventions or integrating CVD into existing intervention

European Hernia Society guidelines on prevention and treatment of parastomal hernias.

International guidelines on the prevention and treatment of parastomal hernias are lacking. The European Hernia Society therefore implemented a Clinical Practice Guideline development project