Biologic therapies for Crohn’s disease: optimising the old and maximising the new

Abstract

The era of biologic agents for the treatment of Crohn’s disease has brought about significant benefits for patients, and since the introduction of infliximab at the turn of the century, the entire field has moved on rapidly. Clinicians now have multiple agents at their disposal and a choice between several different anti-inflammatory mechanisms of action. This has allowed unprecedented improvements not only in symptoms and quality of life for patients previously refractory to conventional treatments but also for demonstrated healing of the intestinal mucosa and resolution of perianal fistulation. However, despite the undisputed efficacy of these agents, there remains a significant proportion of patients who fail to gain a meaningful benefit. Through years of studying infliximab and its counterpart anti-tumour necrosis factor (anti-TNF) agent, adalimumab, we now understand that strategies such as combining use with a conventional immunomodulator or measuring serum levels can help to optimise outcomes and reduce the proportion of patients for whom treatment fails. Work is ongoing to understand whether these principles apply to newer biologics such as vedolizumab and ustekinumab. In addition, novel approaches are being investigated in an attempt to maximise the benefit that these agents could offer. In this article, we summarise these new understandings and consider ways in which they could be integrated into clinical practice for the benefit of patients.

Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

“…However, this is likely of less importance given that there is currently limited consensus for optimal UST trough levels. 20 Further studies are needed to determine whether measuring UST blood levels circumvents variation in drug clearance between patients and allows for easier dose-escalation decisions.…”

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

“…Ustekinumab maintenance dosing regimen differs from other biologicals as two different dosing intervals are suggested depending on the achieved induction response. Dosing q12w is appropriate after successful induction whereas q8w is suggested in the case of inadequate response [20]. In the current study, most patients began their maintenance ustekinumab treatment with q8w dosing.…”

Histological Hallmarks of Mucosal Healing in Inflammatory Bowel Diseases in the Era of Monoclonal Antibodies Therapy: New Insights and Perspectives

“…Therefore, it is correct to state that the assessment of the degree of disease activity cannot disregard the recognition, topographical description, and possible presence in the glandular (crypt abscess) of neutrophilic granulocytes, and that expressions such as “IBD in the quiescent phase” of mild/moderate disease activity may actually increase the diagnostic confusion that revolves around the concept of mucosal healing [ 21 , 23 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”