Assa A.: New biologics and other new therapies for the treatment of IBD

ESPGHAN presents today an encounter with Prof Amit Assa, who like so many of those who have agreed to take part in these podcasts has filled all the posts of the medical-school and medical-administrative cursus honorum, steadily leaping upward from institution to institution.  As of now he is at the Institute of Paediatric Gastroenterology, Shaare Zedek Medical Centre, in Jerusalem, Israel (affiliated with Hebrew University) ; his interests are concentrated on inflammatory bowel disease.  Today he speaks about the modulation of small-molecule therapy, both increasing and decreasing, as disease is stabilized and wanes.

Some patients, he says, respond to corticosteroids or to 5-acetylsalicylic acid alone; some with Crohn's disease must be advanced to tumour necrosis factor inhibitors such as infliximab or adalimumab, which are in efficacy much of a muchness ; some with ulcerative colitis respond better to infliximab than to adalimumab, meaning that to cover all bases in severe, undifferentiated disease, infliximab is the agent of choice.  Serum levels of drug and detection of anti-drug antibodies are important in titrating trough concentrations of small molecules, and in assessing “pharmacologic failure”, when initial measures are unsuccessful in stabilising and reducing disease.  Induction should be accompanied by therapeutic-drug monitoring, allowing modulation of treatment to reduce morbidity as early as possible.

Additional agents, such as anti-integrin or anti-interferon antibodies are not approved for use in children, but they have their place in treatment failure.  The palette of those available is broad, and the names are complex and barbarous – listen with pencil and paper at hand, to take notes of what does what, and accept that your orthography will be approximate at best.  Re-assessment on endoscopy is often in order, with adjustment of therapy as additional (and more precise) data become available :  Switching based on histological activity alone is often partnered by a clinical setback, so be cautious in choosing criteria.

Multiple-agent therapy and “extreme measures” ?  What does the gastroenterologist choose when his of her patient (and he or she) have their backs against the wall ?  Some situations, such as a stenosing and intractably inflamed bowel segment, require surgery initially.  Others call for drug combinations, watching out for excessive immunosuppression ; extraintestinal manifestations (perianal disease, cutaneous disease, cholangiopathy) must be borne in mind.  Surgery, however, can be a necessary fallback.

Literature :

Conrad MA, Kelsen JR.  The treatment of pediatric inflammatory bowel disease with biologic therapies.  Curr Gastroenterol Rep 2020 Jun 15; 22(8):36.  doi:  10.1007/s11894-020-00773-3.  PMID:  32542562.

Baumgart DC, Le Berre C.  Newer biologic and small-molecule therapies for inflammatory bowel disease.  N Engl J Med 2021 Sep 30; 385(14):1302-1315.  doi:  10.1056/NEJMra1907607.  PMID:  34587387

Grossberg LB et al. Review article:  Emerging drug therapies in inflammatory bowel disease.  Aliment Pharmacol Ther 2022 Apr; 55(7):789-804.  doi:  10.1111/apt.16785.  Epub 2022 Feb 15.  PMID:  35166398

Dr. Assa´s favourite song: מחכה - Idan Rafael Haviv https://open.spotify.com/track/3cmplhlwMZyQbuTHThyGe7?si=22085d464bb748d3

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo