Huiyu Lin

Following the expiration of the adalimumab originator patent, there has been a rapid increase in the availability and uptake of adalimumab biosimilars. While chemically and clinically similar in effects, there are substantial non-pharmacological differences in these products. This global review compares the originator versus currently available adalimumab biosimilars, focusing on variations in formulations and patient support systems across different countries. The goal is to provide prescribers with guidance on selecting the most appropriate products. Data on adalimumab biosimilars were collected from global medication registries and Product Information documents, supplemented by direct inquiries to pharmaceutical companies, with data collection completed in September 2024. Experts from nine countries assessed the local patient support system and collaborated to illustrate the diversity of adalimumab. Including the originator, there are 29 adalimumab products available globally. We highlighted products with favorable characteristics, including delivery device, concentration, citrate content, the range of dosages, latex content, and shelf life. Patient support services helped to differentiate these products further, to capture market share. Among the reviewed countries, Australia, the United States, and Canada offered the most comprehensive patient support systems, including injection training, reminders, as well as nursing and other patient support services. This review highlights the global diversity of adalimumab products, emphasizing key usability factors, such as formulation, dosing flexibility, shelf life, and patient support. A comparative table is provided to aid clinicians in selecting the most appropriate option based on individual patient needs.

Background/Aims: Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. Methods: We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. Results: One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Conclusions: Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Biosimilar adalimumabs have improved treatment access, but without any clinical advantage, distributors rely on delivery device design-enhancements, support services, and removal of painful excipients to capture market share. Prescribers, however, are often unaware of these differences. This article compares and contrasts originator versus biosimilar adalimumab agents to identify key differences that might influence adalimumab selection. We reviewed listed adalimumab biosimilars in Australia and compared them to the originator adalimumab. Similarities and differences identified were confirmed with the manufacturers via two rounds of interviews: the first to collate a list of features and benefits of their product, and the second to consolidate and confirm the data. The originator adalimumab Humira [by AbbVie, U.S.A] and four adalimumab biosimilars (Amgevita [by Amgen, U.S.A], Hadlima [by Organon, U.S.A], Hyrimoz [by Sandoz, Switzerland], and Idacio [by Fresenius Kabi, Germany]) are included in this review. Key differences identified include product formulation, dosages available, delivery devices, physician support, patient support, and the supply of other biosimilar products by the company. Adalimumab biosimilars are different from each other with unique advantages and disadvantages likely to influence prescriber and patients. Therefore, the choice of agent should be individualized to the needs of the patient and the healthcare service.

Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.

Background: Chronic liver diseases including non-alcoholic fatty liver disease (NAFLD) are associated with COVID-19 progression. With no signs of the pandemic abating, thousands worldwide are at risk of a severe disease course. Objective: We aimed to describe the epidemiological features, clinical course, treatment and outcomes of our patients with COVID-19 and chronic liver disease.Methods: A retrospective descriptive study of COVID-19 patients with chronic liver disease admitted to the National Centre for Infectious Diseases in Singapore between 29^th February and 2^nd May 2020 was performed. Results: 16 patients had chronic liver disease – 9 had NAFLD. In the NAFLD group, peak ALT was higher (median: 84 U/L vs 38 U/L; P = 0.042) and more patients had hyperlipidaemia (88.9% vs 28.6%; p=0.035), but median Body Mass Index (BMI) was not significantly higher (24.3 kg/m² vs 24.2 kg/m²). NAFLD patients had a poorer clinical course: more required anti-viral medications (66.7% vs 0%; p=0.011), and time to negative swab was longer (24 days vs 13 days; p=0.008). 3 patients had liver cirrhosis (all non-NAFLD). 1 decompensated but none required intensive care unit admission or died.Conclusion: Our results show that in COVID-19 patients with chronic liver disease, those with NAFLD experience a more severe clinical course. In Asians, NAFLD can have poorer prognostic implications, despite them having only mildly raised BMI. We advocate that patients with NAFLD and liver cirrhosis should be closely monitored for COVID-19 disease progression.