EXPERIENCE OF USING TOCILIZUMAB IN THERAPY OF TAKAYASU ARTERITIS IN CHILDREN

The prognosis of Takayasu arteritis (TA) depends on timely and adequate therapy, but in about half of patients, the disease is refractory to standard therapy or recurs against the background of a decrease in the dose of glucocorticoids (GCs). The use of biological disease-modifying antirheumatic drugs (bDMARDs) in the treatment of TA looks promising, however, the experience of their use in TA in children is presented by isolated observations. Objective of the study: to evaluate the efficacy and safety of tocilizumab (TCZ) in the treatment of refractory and recurrent forms of TA in children. Materials and methods of research: the study retrospectively included 9 children who were prescribed TCZ when standard therapy was ineffective. Before starting TCZ therapy, all patients were diagnosed with an active form of the disease. The median duration of TCZ therapy was 24 months. Results: against the background of TCZ therapy, the median ESR decreased from 22 to 5 mm/h (p value <0,01), the level of C-reactive protein from 6 to 0 mg/l (p value <0,025). All patients achieved remission. No relapses were observed. The median GCs dose decreased from 0,377 to 0,15 mg/kg/day for prednisolone, 2 patients with GCs were completely canceled. The ITAS.A activity index decreased from 3–12 (median 7) to 0 in 7 and to 1 in 2 more patients. The drug was well tolerated. Adverse reactions included one case of pityriasis versicolor and one case of postoperative phlegmon of the neck and subclavian region on the right. Conclusion: TCZ has shown efficacy and safety for the induction and maintenance of remission in children with TA. The presented results of the study indicate the prospects for further study of the use of TCZ for TA in pediatric practice.

Will the Inducing and Maintaining Remission of Non-biological Agents and Biological Agents Differ for Crohn's Disease? The Evidence From the Network Meta-Analysis

Background: Several drugs currently are available for the treatment of Crohn's disease, including non-biological agents such as anti-inflammatory agents, steroids, immunosuppressive agents, and biologic agents such as anti-tumor necrosis factor (TNF), anti-α4β7 integrin, anti-alpha-4 integrin and anti-interleukin 12/23. However, the choice of treatments for induction and maintenance is still a challenge. The relevant comparison between non-biologic agents and biologic agents is few. In our research, we aimed to help making decisions, as well as providing clinicians and patients with medication references.Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of controlled trials for relevant randomized controlled trials published through to July 2020 and systematic reviews published from January 2011 to December 2020. Search results were screened by 2 independent reviewers first by title and abstract and then by full text. Disagreements were resolved through discussion with a third reviewer.Results: 54 randomized controlled trials were included in our analysis. For induction of remission, azathioprine (OR, 3.5; 95% Crl, 1.4–8.9), infliximab (OR, 4.1; 95% Crl, 1.2–16.0), infliximab + azathioprine (OR, 7.0; 95% Crl, 1.2–41.0) and infliximab+ methotrexate (OR, 7.8; 95% Crl, 1.2–65.0) were more effective in first-line therapy than placebo. Adalimumab showed superiority to placebo in second-line therapy, but the range of SD was wide. For maintenance of remission, adalimumab (OR,2.24;95% Crl,1.17–4.76) and azathioprine (OR,2.05; 95% Crl,1.14–3.96) were more effective than placebo. Adalimumab (OR,0.56; 95%Crl,0.27–1.2), budesonide (OR,0.63; 95%Crl,0.26–1.6) and natalizumab (OR,0.65; 95%Crl,0.30–1.4) was associated with less risk of withdrawals when compared with placebo.Conclusion: For induction of remission, azathioprine, infliximab, and infliximab + azathioprine were more effective in first-line therapy. In second-line therapy, adalimumab was more effective but should be interpreted carefully. For maintenance of remission, adalimumab and azathioprine were more effective. Besides, adalimumab, budesonide, natalizumab had lower withdrawals. Therefore, biological agents were not always better than non-biological agents and they have their own advantages in different treatment methods of Crohn's disease.

Budesonide (Jorveza)

CADTH recommends that Jorveza should be reimbursed by public drug plans for the maintenance of remission in adults with eosinophilic esophagitis (EoE) if certain conditions are met. Jorveza should only be reimbursed if prescribed by a specialist with experience in the diagnosis and management of EoE, and the cost of Jorveza is reduced. Jorveza should only be covered for adult patients who have a confirmed diagnosis of EoE, in whom treatment with a proton pump inhibitor (PPI) did not work, and whose symptoms (dysphagia and pain during swallowing) have resolved after receiving induction treatment with Jorveza.

Update of Management of ANCA-Associated Vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with significant morbidity and mortality. Management of AAV is divided into induction of remission and maintenance of remission. Management of AAV has evolved with the aim of improving treatment outcomes and minimizing treatment toxicities. In this article, we will review the latest evidence on the treatment of AAV.

Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease

The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors.

Reduced Specificity and Increased Overgenerality of Autobiographical Memory Persist as Cognitive Vulnerabilities in Remitted Major Depression: A Meta-Analysis

Difficulty in accessing specific memories, referred to as reduced memory specificity or overgeneral memory, has been established as a marker of clinical depression. However, it is not clear if this deficit persists following the remission of depressive episodes. The current study involved a systematic review and meta-analysis of empirical studies with the aim of establishing whether remitted depression was associated with retrieving fewer specific and more overgeneral autobiographical memories. Seventeen studies were identified as eligible. The results indicated that people with remitted depression recalled fewer specific memories (k = 15; g = -0.314, 95% CI[-0.543; -0.085], z = -2.69, p = .007) and more categoric memories (k = 9; g = 0.254, 95% CI[0.007; 0.501], z = 2.02, p = .043) compared to people who had never been depressed. Given that these deficits have elsewhere been shown to be prognostic of future depressive symptoms, these findings provide further evidence that reduced memory specificity/overgeneral memory appears to be a risk factor for future episodes of depression in those that are in remission. The findings are discussed in terms of how this knowledge might influence clinical understanding of relapse prevention and maintenance of remission in those with a history of depression.

Safety and Effectiveness of Vedolizumab for the Treatment of Pediatric Patients with Very Early Onset Inflammatory Bowel Diseases

Background: Vedolizumab (vedo) is effective for induction and maintenance of remission in adults with inflammatory bowel disease (IBD). Pediatric data are still limited, especially for the youngest children with very early onset disease (VEO-IBD). The aim of this study was to assess the safety and efficacy of vedo in VEO-IBD. Methods: We performed a retrospective review of pediatric IBD patients with VEO-IBD (defined as aged <6 years) receiving vedo. Data on demographics, disease behavior, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the pediatric Crohn’s disease (CD) activity index (PCDAI) for CD or pediatric ulcerative colitis (UC) activity index (PUCAI) for UC. Primary outcome was clinical response after induction therapy with vedolizumab (4th dose week). It was defined as a decrease in PCDAI of at least 12.5 points between baseline and 4th dose week for CD, and a decrease in PUCAI of at least 20 points between baseline and this time for UC. Descriptive statistics were performed to analyze the data. Results: The study included 16 patients with VEO-IBD who have received vedo: 4/16 (25%) with CD, and 12/16 (75%) with UC at the median age of diagnosis 33.7 months (6.6 months–4.5 years). Median age at vedo initiation was 6.5 years (2.2–16.5 years). Among the analyzed individuals, 56.25% had failed more than one anti-tumor necrosis factor (TNF) alfa agent. Clinical response at 4th dose week was observed in 9/16 (56.3%) patients: mean baseline PCDAI score was 34.4 ± 1.9 and 10.6 ± 1.8 after induction therapy with vedo, while PUCAI score was 26 ± 6 vs. 18 ± 8, respectively. There was improvement in patients’ nutritional state: at baseline 2/16 (12.5%) children had body mass index (BMI) below 1 percentile and no child had such BMI after induction therapy with vedo. No infusion reactions or serious adverse events/infections were reported. Conclusion: Vedolizumab is safe and effective in the medical management of pediatric patients with VEO-IBD.