Gastroenterology

While real-world data, such as those derived from the NOR-SWITCH study, have been reassuring about the feasibility of switching patients with inflammatory diseases from reference infliximab (Remicade) to biosimilar CT-P13 (sold as Inflectra and Remsima), some ambiguous data in patients with inflammatory bowel disease (IBD) have raised questions among clinicians about switching in the indications of Crohn disease and ulcerative colitis.

Fraser Cummings, MBChB, DPhil, led one of the first clinical teams to switch patients receiving the reference infliximab (Remicade) to CT-P13 (Remsima) in UK clinical practice. During the SMi 9th annual conference on Biosimilars and Biobetters, held September 26-27 in London, United Kingdom, Cummings explained his experience with this switch in his gastroenterology clinic, and looked ahead to the arrival of adalimumab biosimilars in the National Health Service (NHS).

Up to 60% of Crohn disease patients taking an anti—tumor necrosis factor (TNF) monoclonal antibody medication eventually stop responding to treatment, but the optimal management of these patients has not been clearly defined.

“The common initiation in North America of infliximab as monotherapy is concerning, given the now substantial body of evidence…documenting the importance of concomitant [immunomodulators] in reducing the likelihood of secondary loss of responsiveness related to anti-infliximab antibodies," write the researchers.

Catch up on the week’s top rheumatology, gastroenterology, clinical practice, regulatory, policy, and business news from the world of biosimilars.

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated, progressive biliary disease that is closely associated with inflammatory bowel disease (IBD). PSC has no cure, and up to 40% of cases eventually require patients to receive liver transplants. Given the efficacy of biologics in treating IBD, the potential to treat PSC with these same drugs is a matter of interest for healthcare providers.

Intestinal Behçet disease (BD), which is an immune-mediated, chronic, inflammatory intestinal disease, can be difficult to treat, in part because the pathogenesis of intestinal BD is unclear. However, as data for using anti–tumor necrosis factor (anti-TNF) drugs have been accumulating in the treatment of inflammatory bowel disease (IBD), which has a similar clinical presentation, the potential to treat BD with these agents is under investigation.

A new study, published in Alimentary Pharmacology and Therapeutics, sought to test antigenic comparability between the reference infliximab and the biosimilar.

Researchers from Spain, where biosimilar use is encouraged as a way to save on costs and expand access to biologic therapies, recently reported on a multicenter prospective observational study in patients with inflammatory bowel disease (IBD) who switched from reference infliximab to a biosimilar, CT-P13 (Inflectra, Remsima).

“I see no reason as a healthcare provider to intentionally go back and forth needlessly, but I see no concerns that, if I do that, bad things would happen,” said Jason Schairer, MD.

Crohn disease (CD) can involve physical, psychological, and social impairments that negatively impact patients’ quality of life, and high levels of anxiety and depression have been observed in patients with CD.

The question of whether to switch patients from a reference biologic to an available biosimilar has been the subject of extensive debate, especially in patients with inflammatory bowel disease (IBD), an indication in which evidence on relevant clinical outcomes after switching is limited.

Celltrion presented new research that demonstrates that a formulation of its infliximab biosimilar intended for subcutaneous administration is comparable to the intravenously administered option. The phase 1 study compared the subcutaneous formulation—which can be self-administered—with the FDA-approved intravenous formulation in patients with active Crohn disease (CD).

This week, the FDA approved an expanded indication of the Janus kinase (JAK) inhibitor tofacitinib (Xeljanz) to include adults with moderate to severe ulcerative colitis. Tofacitinib is the first oral medicine approved for long-term use in UC, and provides an alternative to anti–tumor necrosis factor (anti-TNF) drugs that must be injected or infused.

While it is already known that obesity may contribute to an increased risk developing some immune-mediated inflammatory diseases, as well as more severe disease activity and a higher burden of hospitalization, a new review found that obesity is also a predictor of inferior response to anti–tumor necrosis factor (anti-TNF) agents.

The authors of a recent study report that the addition of a disease-modifying anti-rheumatic drug (DMARD) or a switch to ustekinumab showed greater efficacy than changing anti–tumor necrosis factor (anti-TNF) treatments in patients with inflammatory bowel disease (IBD) who develop paradoxical arthritis.

One of the main concerns attributed to anti–tumor necrosis factor (anti-TNF) treatment during pregnancy is the ability for the therapy to be transferred to the fetus. Complete immunoglobulin G (IgG) antibodies, both maternal and therapeutic, are delivered to the placenta during pregnancy naturally. This fact is important for patients who are treated with adalimumab, golimumab, and infliximab, which are complete IgG1 anti-TNF antibodies, and therefore transferred easily to the placenta.

Although the benefits of originator infliximab have been deemed to outweigh the potential harm during pregnancy, in a recent observational study, researchers looked to evaluate whether biosimilar infliximab therapy was associated with any new safety risks.

While systemic inflammation is a potential biological mechanism underlying both Parkinson disease (PD) and inflammatory bowel disease (IBD), clinical data on comorbid PD and IBD are few. In a new study published in JAMA Neurology, researchers report on a retrospective cohort study that assessed the incidence of PD among patients with IBD and sought to identify whether anti–tumor necrosis factor (anti-TNF) therapy for IBD alters the risk of PD.

The European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), an umbrella organization that represents 34 patient associations around the world, recently released a report on healthcare inequities among nations and regions. In the report, the EFCCA identified disparities in access to biologics and biosimilars.

“A [3]-year time lag for the next biosimilar medicine, from market authorization to the patient switching process, should not occur," say the authors of a recent review.

In patients with IBD, it was found that gut microbial levels lack in diversity. After receiving infliximab treatment, CD patients restored their microbial diversity and increased their Clostridiales levels. Clostridiales reduced proinflammatory bacteria, produced short-chain fatty acids, and induced an immune response.

This week, the Spanish Society of Digestive Pathology (SEPD) became the most recent organization to announce an updated position statement on the use of biosimilars.

This week, Israel-based Protalix BioTherapeutics, Inc, announced positive results from a phase 2 clinical trial for its orally administered anti–tumor necrosis factor (anti-TNF) drug, OPRX-106, a plant cell–expressed recombinant human TNF receptor II fused to an IgG1 Fc domain.

Randomized controlled trials have established the clinical efficacy and safety of infliximab in treating fistulizing Crohn disease (CD), and while evidence for adalimumab and vedolizumab in this indication is weaker, these drugs are also used in clinical practice, sometimes in treatment sequences of biologics, to treat fistulizing CD. In Europe, where access to biologic drugs is largely driven by budgetary considerations, biosimilars have the potential to improve access to treatment.

In an effort to evaluate whether switching from a reference biologic to a biosimilar could lead to altered clinical outcomes—such as enhanced immunogenicity, compromised safety, or reduced efficacy—a research team, led by Hillel Cohen, PhD, conducted a systematic literature review of all available switching studies.

February 2018 saw a number of developments for biosimilars that treat inflammatory bowel disease, with new studies from around the globe adding to the body of data on these therapies.

A study published in Alimentary Pharmacology Therapeutics in December 2017 compared the outcomes, pharmacokinetics, and immunogenicity of treatment intensification strategies in patients with Crohn disease (CD) who have lost clinical response to the anti–tumor necrosis factor (anti-TNF) therapy infliximab.

Last week, at the European Crohn's and Colitis Organisation's 13th annual congress in Vienna, Austria, researchers presented data from the NOR-SWITCH EXTENSION trial—a 26-week open label extension of the NOR-SWITCH trial—concerning the inflammatory bowel disease (IBD) subgroup.

At the recent European Crohn's and Colitis Organisation’s 13th Congress in Vienna, Austria, several studies investigated the efficacy of infliximab biosimilars in treating Crohn disease (CD), ulcerative colitis (UC), and rheumatoid arthritis (RA).