Dr. Joel Rosh gave our group an excellent update on sequencing therapy for ulcerative colitis (UC). My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.
- There are only two FDA-approved biologics in pediatric Ulcerative Colitis. It typically takes 8-10 years for a medication with approval in adults to receive FDA approval in children
- The concept of IBD as two diseases, Crohn’s disease and UC, is flawed; there are more than 200 susceptibility genes for inflammatory bowel disease
- There has been an increasing incidence and prevalence of IBD. Some of this increase is likely due to our diet and its effects on the microbiome
- Ultrasound is a nice tool to see what is going on in real time and shows that UC is really a transmural disease. UC changes in the bowel can result in fibrosis
- Consider cytokine-basis for disease as a way to conceptualize disease presentation compared to organ-based disease. Many autoimmune diseases (eg. JIA, RA, Psoriasis) are different manifestations related to cytokine-based autoimmunity
- Almost all pediatric IBD can be considered higher risk based on known risk factors including disease extent (>80% of pediatric UC is pancolitis) and disease age of onset
- Mesalamine steroid-free clinical remission rates are about 1/3rd after 1 year of treatment
- Overall, there has been an improvement in colectomy rates since 2001; there still appears to be a bump in the colectomy rate after having UC for more than 10 years
- Elevated CRP is less common in patients with UC, compared to Crohn’s disease, and is a marker for more severe disease activity
- Dr. Rosh prefers to avoid some terms including biologic-naive and steroid failure; he favors biologic-unexposed for the former. For the latter, he tries to make it clear that the patient was not a steroid failure. Steroids failed the patient rather than the patient failing the steroids
- Therapeutic drug monitoring (TDM) is mainly beneficial for anti-TNF agents at this time. Use of TDM can help monotherapy achieve similar results as combination therapy. For infliximab, Dr. Rosh’s ‘rule of thumb’ is 28-18-8 for 2 week trough, 6 week trough, and maintenance trough. Therapeutic levels will meet or exceed these trough levels.
- Combination therapy has not been shown to improve pharmacokinetics for vedolizumab or ustekinumab
- Generally, a washout period is not needed when changing biologic therapies. In fact, having some overlap in the medications may have some therapeutic benefit
- Upadacitinib (Rinvoq) appears to be the most effective JAK for IBD. It is labelled for use as a 2nd-line agent but may be superior for some sicker patients. Rinvoq could be considered as a ‘bridge’ medication in patients with acute severe ulcerative colitis with transition to another biologic like vedolizumab
- It is important for families to be informed that there is a black box warning for the use of JAK inhibitors. However, major cardiac adverse events (MACE) do not appear to be increased in patients without preexisting cardiac disease risk factors
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