Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

Platelet activation and hypercoagulability in patients with early primary biliary cholangitis compared with healthy controls

Background Patients with primary biliary cholangitis (PBC) who have advanced disease are hypercoagulable, with no thrombophilic factors compared to non-cholestatic cirrhotics. We investigated whether hypercoagulability is present in early-stage PBC. Methods PBC patients with biopsy-documented early disease and healthy controls matched by sex and age were asked to participate in the study. All were evaluated using rotational thromboelastometry (ROTEM), platelet aggregation, and flow cytometry. Four ROTEM parameters were evaluated (clotting time, clotting formation time, α-angle, and maximum clot firmness [MCF]). Platelet aggregation was determined as the maximal change in light transmission after the addition of adenosine diphosphate, collagen and epinephrine. Flow cytometry was used to evaluate the expression of glycoprotein (GP) IIb, GPIIa, and P-selectin on the platelet surface. Results We enrolled 50 individuals in the study (25 PBC patients, 25 controls). Prothrombin time and activated partial thromboplastin time did not differ significantly between PBC patients and controls (P-value not significant). In ROTEM, α-angle and MCF parameters were abnormally elevated in 9 (36%) PBC patients compared to 3 (12%) healthy controls and the difference was statistically significant (P=0.026). Platelet aggregation in PBC patients was not significantly different from controls. In flow cytometry, GPIIb and P-selectin expression was greater in PBC patients than in the control group and the difference was statistically significant (P=0.005 and P=0.006 respectively). Conclusion In this study, we used a combination of sophisticated methods to detect evidence of platelet activation and hypercoagulability in patients with early PBC. Our findings may have important clinical implications and merit further investigation. © 2021 Hellenic Society of Gastroenterology

Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis

TL1A is a novel TNF-tike cytokine, which provides co-stimulatory and Th1-polarizing signals to activated lymphocytes, via binding to death-domain receptor 3 (DR3). These functions are inhibited when TL1A associates to decoy receptor 3 (DcR3). We investigated the serum expression of TL1A and DcR3 in 81 patients with RA and 51 healthy controls. TL1A concentrations were elevated in patients by 5-fold (P<0.00001). This increase was more prominent in RFactor-positive patients and correlated with clinical activity in this subgroup. DcR3 was detected more frequently and in significantly higher values in RA-derived sera, correlated strongly with TL1A, and was present in inflammatory synovial fluid. Severe RA stage was associated with highly elevated TL1A and DcR3 serum levels. Treatment with an anti-TNF agent significantly decreased TL1A serum levels. We conclude that TL1A may serve as an inflammatory marker in RA. Interactions between TL1A and its receptors may be important in the pathogenesis of RA. (C) 2008 Elsevier Inc. All rights reserved

Atypical mycobacterial infection presenting as persistent skin lesion in a patient with ulcerative colitis

Immunosuppressive drugs are commonly used for the treatment of inflammatory bowel disease. Patients receiving immunosuppressants are susceptible to a variety of infections with opportunistic pathogens. We present a case of skin infection with Mycobacterium chelonae in a 60-year-old Caucasian woman with ulcerative colitis who had been treated with corticosteroids and azathioprine. The disease manifested with fever and rash involving the right leg. Infliximab was administered due to a presumptive diagnosis of pyoderma gangrenosum, leading to worsening of the clinical syndrome and admission to our hospital. Routine cultures from various sites were all negative. However, Ziehl-Neelsen staining of pus from the lesions revealed acid-fast bacilli, and culture yielded a rapidly growing mycobacterium further identified as M. chelonae. The patient responded to a clarithromycin-based regimen. Clinicians should be aware of skin lesions caused by atypical mycobacteria in immunocompromised patients with inflammatory bowel disease. Furthermore, they should be able to thoroughly investigate and promptly treat these conditions. © 2011 Giorgos Bamias et al

Significance of definitions of relapse after discontinuation of oral antivirals in HBeAg-negative chronic hepatitis B

Relapses are observed in most hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long-term NA therapy. In total, 130 HBeAg-negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on-therapy virological remission for ≥24 months and close follow-up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on-therapy virological remission was 43 months. During a median off-NAs follow-up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%-49%, 4%-73%, 11%-82%, and 16%-90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. Conclusion: In HBeAg-negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off-NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off-NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (Hepatology 2017). © 2017 by the American Association for the Study of Liver Diseases

High prevalence of asymptomatic peptic ulcers diagnosed during screening endoscopy in patients with cirrhosis

Background Peptic ulcer disease (PUD) is more prevalent in cirrhotics and this may aggravate prognosis. We investigated the prevalence of PUD in cirrhotics and its potential association with Helicobacter pylori (H. pylori) infection, the underlying etiology and severity of liver disease, and other manifestations of portal hypertension (PH). Methods We enrolled consecutive asymptomatic cirrhotic patients who underwent screening endoscopy in a tertiary hospital during a 12-month period. We recorded the presence of PUD and the endoscopic findings associated with PH. H. pylori infection was documented through either histology or CLO-test. The diagnosis of cirrhosis was based on elastography, liver biopsy or a combination of clinical, biochemical and imaging data. Results One hundred patients (M/F: 54/46, mean age: 61±14 years) were included in the analysis. Viral hepatitis (37%) and alcohol (22%) were the most common causes of cirrhosis. Child-Pugh stage was A/B/C: 60/35/5. PUD was found in 19 patients (14 gastric, 5 duodenal). H. pylori infection was diagnosed in 54%. Varices were detected in 59% (39% needed treatment). PH gastropathy was present in 81% (severe in 33%). The presence of PUD was unrelated to the etiology and the severity of liver disease or to other endoscopic manifestations of PH. No correlation was found between PUD and H. pylori infection. Conclusions A high prevalence of PUD was observed in our cirrhotic patients, although they were asymptomatic and had no known risk factors of ulcerogenicity. The value of screening endoscopy for the early diagnosis and treatment of PUD in cirrhotics deserves further investigation. © 2019 Hellenic Society of Gastroenterology

Correlation of Impedance Threshold Device use during cardiopulmonary resuscitation with post-cardiac arrest Acute Kidney Injury

Purpose To assess whether use of Impedance Threshold Device (ITD) during cardiopulmonary resuscitation (CPR) reduces the degree of post-cardiac arrest Acute Kidney Injury (AKI), as a result of improved hemodynamics, in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods After 8 min of untreated cardiac arrest, the animals were resuscitated either with active compression-decompression (ACD) CPR plus a sham ITD (control group, n = 8) or with ACD-CPR plus an active ITD (ITD group, n = 8). Adrenaline was administered every 4 min and electrical defibrillation was attempted every 2 min until return of spontaneous circulation (ROSC) or asystole. After ROSC the animals were monitored for 6 h under general anesthesia and then returned to their cages for a 48 h observation, before euthanasia. Two novel biomarkers, Neutrophil Gelatinase-Associated Lipocalin (NGAL) in plasma and Interleukin-18 (IL-18) in urine, were measured at 2 h, 4 h, 6 h, 24 h and 48 h post-ROSC, in order to assess the degree of AKI. Results ROSC was observed in 7 (87.5%) animals treated with the sham valve and 8 (100%) animals treated with the active valve (P = NS). However, more than twice as many animals survived at 48 h in the ITD group (n = 8, 100%) compared to the control group (n = 3, 37.5%). Urine IL-18 and plasma NGAL levels were augmented post-ROSC in both groups, but they were significantly higher in the control group compared with the ITD group, at all measured time points. Conclusion Use of ITD during ACD-CPR improved hemodynamic parameters, increased 48 h survival and decreased the degree of post-cardiac arrest AKI in the resuscitated animals. © 2017 Elsevier Inc

Monitoring and comorbidities in patients with chronic hepatitis B currently treated with nucleos(t)ide analogs

Background Long-term monotherapy with nucleos(t)ide analogs (NAs) represents the treatment option for the majority of patients with chronic hepatitis B (CHB), an aging population with a greater likelihood of comorbidities. We assessed the prevalence of concurrent non-hepatic diseases and the safety monitoring in a large cohort of CHB patients receiving NAs and their potential impact on disease outcomes. Methods We included 500 consecutive CHB patients from 5 major tertiary Greek centers, under long-term therapy with an NA. Epidemiological/clinical characteristics and data on concomitant disease, drug use and investigations ordered were collected. Results The mean age was 58 years and 66% were male. Most patients were receiving tenofovir disoproxil fumarate (TDF, 60%) or entecavir (ETV, 37%) monotherapy. Decompensated cirrhosis at baseline was present in 10%, while hepatocellular carcinoma (HCC) under therapy developed in 21 patients. The median duration of total NA therapy was 56 and of latest therapy 42 months. The most common (prevalence >10%) comorbidities were hypertension (28%), non-HCC cancer(s) (12%), and diabetes (11%). Patients with a longer duration of latest therapy (≥4 vs. <4 years) were older (mean age: 58 vs. 56 years, P=0.004), had more frequent history of prior use of NA(s) (53% vs. 35%, P<0.001), and less frequent liver decompensation (5% vs. 13%, P=0.008) and non-HCC cancers (8% vs. 15%, P=0.020). HCC developed more frequently in patients with than in those without diabetes (11% vs. 3%, P=0.022). Conclusion Greek CHB patients currently treated with NAs, almost exclusively ETV or TDF, are often older than 60 years, have several comorbidities, and thus require careful management. © 2021 Hellenic Society of Gastroenterology