Clinical and Biological Predictors of Response to Standardised Paediatric Colitis Therapy

By Katie E. Golden

There is currently inadequate evidence-based research to guide the development of treatment regimens in Inflammatory Bowel Disease (IBD), which unfortunately translates to a large variation in therapeutic approaches and poorly predicted treatment response. Researchers are trying to change that with the PROTECT trial, a multicenter study investigating pediatric patients diagnosed with Ulcerative Colitis (UC), a form of IBD. In a recently published cohort study published in The Lancet, Hayams et.al. sought to identify pretreatment clinical and microbiome factors that predict disease course and response to treatment.1

In their study, investigators recruited pediatric patients (ages 4 to 17) with newly diagnosed UC across centers in the USA and Canada. Prior to initiation of treatment, they collected fecal samples, blood tests, and intestinal tissue biopsies. Patients then received either mesalazine or steroids for initial treatment, with pre-established protocols for escalation to more advanced therapies (thiopurines or anti-TNF╬▒ therapy) in the circumstance of treatment failure. Their primary outcome was steroid-free remission at 1 year, with no advancement of intervention beyond mesalazine. Their secondary outcome was escalation to the advanced drug regimens or colectomy.

The investigators were able to recruit over 400 patients, of which 386 completed the study period without any violations. They found that low baseline clinical severity, and clinical remission at week 4 of treatment were significantly associated with 1 year steroid-free remission. This finding could have important implications to guide clinical decisions for when treatment alternatives should be considered in specific patient populations. They also found that patients were more likely to need need more advanced interventions if they had low baseline Vitamin D levels, as well as low intestinal mucosa eosinophil levels on rectal biopsies. Additionally, after adjusting for clinical predictors, they found that gene expression of antimicrobial peptides, along with two specific microbial species (Ruminococcaceae and Sutterella) were independently associated with disease remission at 1 year. Their cumulative findings are an important step towards the development of more targeted, personalized therapeutic approaches to UC treatment.

  1. Hyams JS, Davis Thomas S, Gotman N, Haberman Y, Karns R, Schirmer M, Mo A, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo PA, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis MA, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Saul B, Wang J, Serrano J, Hommel K, Marigorta UM, Gibson G, Xavier RJ, Kugathasan S, Walters T, Denson LA. Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study. Lancet. 2019 Mar 29.