A recent large retrospective pediatric study provides further evidence that therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) results in better clinical outcomes. One of my partners, Chelly Dykes, is a coauthor and leads our ImproveCareNow team.
This single center implemented a practice wide TDM approach in 2014. This study compared a historical pre-TDM group (n=108) to the TDM group (n=206). The primary outcome was sustained clinical remission (SCR22-52), defined as physician global assessment (PGA) of inactive from 22 to 52 weeks and off corticosteroids at 52 weeks. Key findings:
The SCR22-52 was achieved in 42% of pre-TDM and 59% of TDM patients (risk difference, 17.6%; 95% CI, 5.4–29%; P = 0.004)
The TDM group had an increased adjusted odds of achieving SCR22-52 (odds ratio, 2.03; 95% CI, 1.27–3.26; P = 0.003)
The adjusted risk of developing high titer antidrug antibodies (ADAs) was lower in the post-TDM group (hazard ratio, 0.18; 95% CI, 0.09–0.35; P < 0.001)
The SCBR22-52 (which was defined by normal CRP along with SCR22-52) was 24.7% in pre-TDM and 42.7% in the TDM group
The authors did not identify a significantly higher rate of anti-TNF cessation in either group
Only 12% of patients in their practice were receiving combination therapy
In the discussion, the authors review three pivotal studies which also support proactive TDM: TAXIT, TAILORIX, and PAILOT.
My take: While this was an observational study with historical controls, the findings are convincing that proactive TDM is helpful, particularly in patients who are not receiving combination therapy.
AGA 2017 Guidelines on Therapeutic Monitoriing Proactive drug monitoring: “careful and selective use of proactive TDM could be beneficial, but current evidence for its routine use is limited and its overall benefits remain uncertain”
The authors retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown.
Key finding: Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34–5.41; P = .005).
This retrospective study had 235 patients (median age 38 years). 90% had endoscopy at a median of 2 days from admission. Key findings:
155 of the 235 patients (66.0%) responded to steroids
78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician’s global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%).
Comparison with Truelove and Witts Score: 56 of 119 (47.1%) of those classed TWS severe did not respond to steroids. Previously TWS score of acute severe ulcerative colitis (ASUC), defined by at least 6 bloody stools per day plus at least 1 marker of systemic disturbance has been associated with a 19% risk of colectomy during admission.
My take: In patients with ulcerative colitis who present with low albumin and high CRP values, early escalation of medical therapy is highly likely; don’t forget to check a PPD or quantiferon Gold assay early on.
Dr. Joseph D. Feuerstein, gastroenterologist at Beth Israel Deaconess Medical Center in Boston… “It’s rising in incidence and prevalence throughout the world,” he said, and gastroenterologists are still trying to figure out why it shows up when it does in different people.
Crohn’s disease was first described in 1932 by Dr. Burrill B. Crohn…
Prompt diagnosis and appropriate therapy to suppress inflammation in the digestive tract are extremely important because a delay can result in scar tissue and strictures that are not reversed by medication…
Crohn’s is not curable and most patients have to stay on medication indefinitely. That can create yet another stumbling block. The biologics are very costly…
This study prospectively assessed for mucosal healing by endoscopy 3 to 5 months after clinical remission, PUCAI <10, was documented. Key findings:
28 children in continuous clinical remission at time of sigmoidoscopy were included. Mayo 0 was present in 12/28 (43%), Mayo 1 in 2/28 (7%) and Mayo 2 to 3 in 14/28 (50%) endoscopies.
Among 23 patients with follow-up through 18 months, remission was sustained in 6/12 (50%) with Mayo score 0 to 1 versus 2/11 (18%) of patients with Mayo 2 and 3
16 (57%) of the patients were receiving 5-ASA treatment
It would have been helpful to have calprotectin values as well. In their discussion, the authors note that “a normal calprotectin is quite convincing with regard to endoscopic remission” and ECCO ESPGHAN guidelines “provide guidance that a colonoscopy should only be performed if fecal calprotectin” is >250 mcg/g.
My take: Clinical remission in ulcerative colitis should be verified. It is reasonable to start with a fecal calprotectin and if elevated to proceed with endoscopic evaluation (colonoscopy or sigmoidoscopy).
Also: new therapy for Crohn’s disease with favorable phase III study. From Pharmacy Times: Risankizumab (Skyrizi) Demonstrates Significant Improvements In Patients with Crohn Disease Two studies, ADVANCE and MOTIVATE showed similar results for Crohn’s disease. In the ADVANCE study: “40% of patients receiving 600 mg, and 32% of patients receiving 1200 mg achieved endoscopic response at week 12, compared to 12% in the placebo group.” In the MOTIVATE study, “29% and 34% of patients receiving 600 mg and 1200 mg achieved endoscopic response, respectively, compared to 11% in the placebo group.”
In this PIANO study (2007-2019), pregnant women with IBD were enrolled in a prospective, observational, multicenter study across the United States. PIANO is an acronym for Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes.
In this study, which analyzed Medicaid Analytic eXtract data from 4 states (California, Georgia, North Carolina, and Texas) between 2006 and 2011, the authors identified 14,735 patients with IBD (4672 black [32%]). Key finding: “In patients with Medicaid insurance, where access to IBD-specific therapy should be similar for all individuals, there was no significant disparity by race in the utilization of IBD-specific therapies.”
This was a retrospective cohort study which included 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking.
Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04–2.9; P = 0.034)
Smoking has long been identified as one of the strongest environmental risk factors for both the development of Crohn disease (CD) and the worsening of the disease course.
Studies in smokers with CD have reported that the risk of flares and complications matches that of nonsmokers with CD after 1 year of abstinence.
It would be reasonable to expect that a similar risk reduction exists for patients who can become passive-smoke-free. In addition, their likelihood of remaining smoke-free themselves is increased if they live in a smoke-free household.
My take (from editorial): “Clinicians should consider widening the scope of smoking cessation counseling to include not just patients but also their cohabitants.”
This is a very useful article. Table 3 lists many of the features of some monogenic inflammatory bowel disease (IBD). Table 4 details potential immune workup tests. Table 5 lists 75 genes that should be included when testing for monogenic IBD.
Box 2 (see below) provides a list of conditions that should prompt consideration of genetic testing. Figure 1 provides an algorithm for testing.
Table 6 provides a summary of statements
#3:”Genetic screening for monogenic IBD is recommended in all patients with infantile-onset IBD (<2 years) and should be considered in patients with very early-onset IBD (<6 years), in particular, in those patients with relevant comorbidity, extraintestinal manifestations, and/or family history”
#5: “Routine genetic screening for all IBD patients is not recommended since a monogenic cause of IBD in patients with IBD onset over 6 year of age, especially those with adolescent or adult age onset of IBD is exceptional in the absence of relevant comorbidity”
There is also some advice on variants of unknown significance: “Databases, such as Clinvar, ClinGen, or The Human Gene Mutation Database can help to assess variant phenotype relations”
In patients receiving anti-TNF agents which are usually effective for CRMO, CRMO may develop paradoxically and may be associated with a psoriaform reaction.
At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti–anti-TNFα antibodies.
All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1).
My take: This study describes a rare adverse effect of anti-TNFα agents. If CRMO develops while on one of these agents, an alternative treatment is needed.
Background: 10% of healthy subjects are genetically at high risk for thromboembolic disease (TED). For adults with inflammatory bowel disease, TED is “largest cause of mortality in patients”
In total, this retrospective study had 792 IBD patients who had both whole-exome sequencing and genotyping data to identify thrombophilia pathogenic variants. 122 of 792 IBD patients (15.4%) as genetically high risk for TED.
Genetic TED risk was significantly associated with increased TED event (odds ratio,2.5; P ¼ .0036).
Patients with high TED genetic risk more frequently had thrombosis at multiple sites (78% vs 42%, odds ratio, 3.96; P ¼ .048)
“Our analyses demonstrate that approximately 1 in 7 patients with IBD have odds 2.5 times higher than nongenetically high-risk patients with IBD for experiencing TED.” The risk of TED in IBD is generally 3- to 4-fold higher than the general population
My take: In children, the risk of clots is much lower than in adults. Thus, the potential to identify those at highest risk would be useful in order to target interventions. Also, patients at higher risk for TED may affect choice of treatment (eg. avoiding JAK inhibitors).