Inhomogeneous Diastereomeric Composition of Mongersen Antisense Phosphorothioate Oligonucleotide Preparations and Related Pharmacological Activity Impairment.

Mongersen is a 21-mer antisense oligonucleotide designed to downregulate Mothers against decapentaplegic homolog 7 (SMAD7) expression to treat Crohn's disease. Mongersen was manufactured in numerous batches at different scales during several years of clinical development, which all appeared identical, using common physicochemical analytical techniques, while only phosphorous-31 nuclear magnetic resonance (P-NMR) in solution showed marked differences. Close-up analysis of 27 mongersen batches revealed marked differences in SMAD7 downregulation in a cell-based assay.

Explaining biosimilars and how reverse engineering plays a critical role in their development.

Introduction: Biologicals are protein-based therapeutics consisting of larger and more complex structures than small molecule medicines. As the patents for originator biological therapeutics expire, biosimilar products are licensed for the same indications as their marketed reference biologics across different specialities. Owing to the complex nature of the manufacturing process for a biological therapy compared to conventional chemically synthetized medicines, the development of biosimilars is more complicated and costly than the manufacture of generic small molecules.

The unleashing of the immune system in COVID-19 and sepsis: the calm before the storm?

The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19.

Can we wean patients with inflammatory arthritis from biological therapies?

Biological therapies have represented a cornerstone in the treatment of immune-mediated inflammatory diseases. Their advent combined with implementation of a treat-to-target approach has meant that remission or low disease activity are now realistic targets for treatment achieved by a significant number of patients. However, biologicals are not risk free and their elevated costs continue to present an important economic burden to national healthcare services.

Adalimumab Biosimilars in Europe: An Overview of the Clinical Evidence.

Adalimumab, the first fully humanised monoclonal antibody against tumour necrosis factor alpha (TNF-α), has played a leading role in the revolution brought about by the introduction of biologics, and has received the widest range of indications among TNF-α inhibitors. Post-registration, observational and registry studies of real-life use have largely supported the outcomes seen in registrational clinical trials. With the recent loss of exclusivity for the originator medicinal product in Europe, a number of biosimilar adalimumab molecules have been licensed for use in the same indications as the originator molecule across rheumatology, dermatology, gastroenterology and ophthalmology.

A review article on biosimilar infliximab SB2 in the treatment of rheumatoid arthritis.

TNF inhibition has had a major impact as an approach for treating rheumatoid arthritis and a series of biologic agents directed against TNF have been developed for clinical use. Infliximab, a chimeric monoclonal antibody against soluble and membrane-bound TNF-α, was the biopharmaceutical to lead this 'biologics revolution'. However, with expiration of patent protection of the originator medicinal product, biosimilar versions of infliximab have been developed through biosimilarity studies and randomized controlled trials aiming to assess pharmacokinetic, pharmacodynamic and clinical equivalence to their originator (reference product) in patients with moderate-to-severe disease activity.

Necrotizing Panniculitis as an Uncommon Manifestation of Acute Pancreatitis.

Unlabelled: Pancreatic panniculitis is a rare disorder affecting 2-3% of patients with pancreatic disease. The findings are characterized by tender, erythematous, subcutaneous nodules which may undergo spontaneous ulceration with discharge of brownish and viscous material derived from colliquative necrosis of adipocytes. The lesions are usually localized in the lower limbs, although they may also extend to the buttocks and also involve the trunk, upper limbs and scalp.

Weekly low-dose methotrexate for reduction of Global Initiative for Asthma Step 5 treatment in severe refractory asthma: study protocol for a randomized controlled trial.

Background: Patients with chronic severe asthma (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these patients due to major methodologic drawbacks, findings with low-dose methotrexate (MTX) are encouraging.

5-aminosalicylic acid enhances anchorage-independent colorectal cancer cell death.

Resistance to anoikis, the cell death triggered by the loss of anchorage to the substratum, is an essential prerequisite in the proliferation and diffusion of colorectal cancer (CRC) cells. We examined whether 5-aminosalicylic acid (5-ASA), a drug that seems to reduce the risk of colitis-associated CRC, enhances CRC cell anoikis. To this end, Colo205 cells were treated with 5-ASA in the presence or absence of inhibitors of caspases (zVAD-fmk) and reactive oxygen species (ROS).