Does the Introduction of Biosimilars Change Our Understanding about Treatment Modalities for Inflammatory Bowel Disease?

BACKGROUND: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use. CONCLUSIONS: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics.

Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by low immunoglobulin (Ig)G and IgA, and/or IgM. In addition to bacterial infections, a large subgroup has noninfectious inflammatory and autoimmune complications. We performed 16S ribosomal RNA-based profiling of stool samples in 44 CVID patients, 45 patients with inflammatory bowel disease (disease controls), and 263 healthy controls. We measured plasma lipopolysaccharide (LPS) and markers of immune cell activation (i.e., soluble (s) CD14 and sCD25) in an expanded cohort of 104 patients with CVID and in 30 healthy controls. We found a large shift in the microbiota of CVID patients characterized by a reduced within-individual bacterial diversity (alpha diversity, P<0.001) without obvious associations to antibiotics use. Plasma levels of both LPS (P=0.001) and sCD25 (P<0.0001) were elevated in CVID, correlating negatively with alpha diversity and positively with a dysbiosis index calculated from the taxonomic profile. Low alpha diversity and high dysbiosis index, LPS, and immune markers were most pronounced in the subgroup with inflammatory and autoimmune complications. Low level of IgA was associated with decreased alpha diversity, but not independently from sCD25 and LPS. Our findings suggest a link between immunodeficiency, systemic immune activation, LPS, and altered gut microbiota.

Anaemia in inflammatory bowel disease: a population-based 10-year follow-up.

BACKGROUND: The point prevalence estimates of anaemia in patients with inflammatory bowel disease (IBD) range between 6% and 74%. The variation is probably due to differences in the definition of anaemia and the study populations. AIM: To retrospectively determine the prevalence of anaemia at diagnosis and at the 1-, 5- and 10-year follow-ups in patients with IBD from a prospectively followed, population-based inception cohort (the IBSEN Study). To compare the prevalence of anaemia after a 10-year disease course with the prevalence of anaemia in the background population, and to assess clinical factors associated with anaemia at diagnosis and during follow-up. METHODS: Newly diagnosed IBD patients were included in a population-based, prospective cohort. Follow-up was performed at 1, 5 and 10 years. All visits included clinical examinations and blood samples. Anaemia was defined according to the WHO. RESULTS: A total of 756 patients (UC, n = 519 and CD, n = 237) were included; 48.8% of CD and 20.2% of UC patients were anaemic at diagnosis (P < 0.001). The proportion of patients with anaemia decreased during the disease course in all patients, except in women with CD. After 10 years of disease, the relative risk for anaemia was increased in all groups, except for women with UC. The variables associated with anaemia were generally unchanged during the disease course, and elevated CRP was the strongest predictor of risk. CONCLUSIONS: Anaemia was more common in CD than in UC. The prevalence of anaemia decreased during the disease course. Women with CD were at high risk for anaemia. Elevated CRP was independently associated with anaemia.