Methods: “GALAXI-2 and GALAXI-3 were identically designed, phase 3, randomised, double-blind, triple-dummy, treat-through trials with active and placebo comparators…1048 participants were randomly assigned, treated, and followed up until week 48, of whom 1021 participants were included in the primary analysis population: 508 (49·8%) in GALAXI-2 and 513 (50·2%) in GALAXI-3.” The studies enrolled adult patients with moderately to severely active Crohn’s disease.
Key findings:
Discussion points:
“Guselkumab treatment in participants with moderately to severely active Crohn’s disease was also evaluated in the GRAVITI study, which had a fully subcutaneous induction and maintenance treatment regimen. Clinical and endoscopic outcomes reported with subcutaneous guselkumab induction in the GRAVITI study were similar to those in the phase 3 GALAXI studies following intravenous guselkumab induction.”
“The incidence of adverse events with guselkumab during induction was low and similar to placebo.”
My take(borrowed from authors): In GALAXI-2 and GALAXI-3, both guselkumab dose regimens (each including intravenous induction and subcutaneous maintenance) were superior to placebo for short-term (week 12) and long-term (week 48) endpoints and both guselkumab dose regimens were also superior to ustekinumab
From editorial (which is more expansive than the study):
Kappelman et al4 report the US prevalence of pediatric-onset IBD (diagnosed before the age of 20 years by a physician) as well as rates of disease based on race and ethnic background. To ensure that a representative population was captured, they combined multiple health administrative databases…
The authors report that the US currently has a pediatric IBD prevalence of 125 per 100,000 population, increased from 110 per 100,000 in 2011. This is higher than previously reported in Canada (82 per 100,000 in 2023)6 and Sweden (75 per 100,000 in 2010).7These differences may be due to the older age cutoff used in the US data, <20 years vs <18 years in the Canadian and Swedish studies. However, misclassification bias may also play a role...
Nevertheless, understanding the approximate prevalence of pediatric IBD in the US allows for adequate human and financial resource planning for this important population of children with an impactful chronic disease. The high prevalence should raise concerns among health care practitioners and policy makers that we have under-resourced IBD care in children, especially considering the high rate of use of biologics and the growing direct health costs incurred in the treatment of this population.11
The burden of IBD in pediatrics goes beyond that of the child. Compared with adult IBD, it disproportionately affects caregivers and families (owing to missed work for appointments, hospitalizations, and home care), mental health of both the patient and the parents, and the health system...
They report that pediatric IBD is more frequent among White children and adolescents (145 per 100,000) compared with Black (91 per 100,000) and Hispanic (88 per 100,000) children, whereas children of Asian origin have markedly lower rates (52 per 100,000).“
My take: The updated prevalence data helps understand the increasing frequency of pediatric IBD. The associated commentary reminds us of the broader burden the disease has for families and for our communities.
This was a cross-sectional observational study in pediatric IBD-patients (n=238) with 104 (43.6%) with Crohn disease (CD), 130 (54.6%) with ulcerative colitis (UC) and 4 (1.6%). Only patients who filled out the Rome IV questionnaire for FC, through dedicated symptom recall at the next clinic appointment or telephone recall, were finally enrolled in the study for subsequent analysis.
Key findings:
Forty-seven out of 238 (19.7%) had a functional constipation history before the IBD diagnosis. In the CD children the prevalence of constipation before the IBD diagnosis was 19/104 (18.2%) and in the UC patients was 28/130 (21.5%).
The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively)
There was a delay in the diagnosis of patients with preceding constipation
Discussion Points:
The main limitations of the present study are certainly related to the retrospective nature and, therefore, the possibility of recall biases must be taken into account.
Rectal bleeding that persists despite stool softener therapy should be investigated
My take: While this study shows that constipation is fairly common prior to a diagnosis of IBD, many times a parent is told that their child is constipated on the basis of an xray or simply because the child complained of stomach pain. This likely increases the risk of recall bias. My guess is that a prospective study involving careful questioning at the time of the initial colonoscopy would yield a lower number of children who had constipation at the time of diagnosis.
Methods: In this prospective cohort study, consecutive adults (n=271) from 2 large IBD centers in Israel with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQs) using a predefined inflammatory bowel disease Mediterranean diet score (IBDMED score), alongside validated MED adherence screeners. Crohn’s disease activity index (CDAI), C-reactive protein, fecal calprotectin, and microbial composition (16S-ribosomal RNA sequencing) were assessed each visit. Baseline serum and fecal samples were analyzed for targeted quantitative metabolomics.
Demographic/Clinical data indicate 68% received biologics and 40% receiving immunomodulators. 32% received 5-ASA medications (despite lack of proven efficacy)
Key findings:
Adherence to MED was associated with a noncomplicated CD course, and inversely correlated with CDAI, fecal calprotectin, C-reactive protein, and microbial dysbiosis index (all P < .05)
Increasing adherence to MED over time correlated with reduced CDAI and inflammatory markers (P < .05)
Adherence to MED correlated with a beneficial microbial cluster of commensals and short-chain fatty acid producers including Faecalibacterium, and with plant metabolites, vitamin derivatives, and amino acids
Adherence to MED in the cohort group was comparable to the general non-IBD population in Israel
Limitations: This was an observational study rather than an interventional study with a control group. Thus, the results could be influenced by reverse causality
In the associated commentary by Abreu et al, it is noted that in Israel, “MED is more commonplace than in the US and other Western countries…Godny et al found that IBD patients had an average MED adherence score of 7.8, which is similar to that of the general non-IBD population in Israel; in contrast, the average MED adherence score in the US is 4–5.Godny et al’s CD patients consumed an average of 21 g of fiber per day; in a study we just completed, American CD patients consumed less than half that amount.13 Indeed, the baseline diets of American IBD patients are characterized by high amounts of saturated animal fat and almost no fresh fruits and vegetables…Another difference between the Israeli population and the typical American population is body mass index (BMI). The average BMI of patients in this study was 21.9 kg/m2 (interquartile range 20–25.3 kg/m2). This contrasts with the average BMI of the general US population of 30 kg/m2.”
My take: This study shows an association between MED diet and better outcomes/less complications in adults with Crohn’s disease. Eating a good diet is an important part of treatment.
Additional notes on dietary scores: “The IBDMED screener positively scored high consumption of MED-recommended dietary components such as fruits, vegetables, olive oil, legumes, nuts and seeds, and fish. It also positively scored low consumption of MED non-recommended dietary components such as red and processed meat, soft drinks, and sweets. To this we added several dietary features based on previous data associated with microbial composition and function. These included a positive score for plant diversity27 by scoring for different colors in the diet, consumption of fermented foods28 (specifically yogurt), and inclusion of starchy vegetables like potato in the whole grain category to promote diversity in the carbohydrate-rich food group, as well as support butyrate producers as we had previously shown.29 In addition, we aimed to positively score for relatively low UPF intake. To this end, we evaluated the average intake of sweets, snacks, sweet and savory pastries, soft drinks, and foods and drinks containing artificial sweeteners.”
Also, from Kim Beall, Cofounder and Managing Director of Nutritional Therapy for IBD:
“If you haven’t been to the website recently, we have expanded the recipe database to over 1,000 recipes with many filterable aspects and we’ve just released a new nutrition tool, the IBD Nutrition Navigator to facilitate nutrition conversations between providers and patients to find the right nutritional starting point. This is a project led by Dr. Ananthakrishnan and a dedicated team of pediatric and adult medical advisors in a two year long development process. Many have told us this is a useful tool particularly for those less familiar with nutrition in IBD. We’re excited about it’s potential to integrate nutrition in practice, with “an option for every patient”. We appreciate your support in sharing our information, tools, and resources to advance IBD nutrition care.” Here’s the link to their website:
This was a prospective, double-blind, placebo-controlled trial with 204 patients examining the clinical outcomes of anti-TNF with or without methotrexate (COMBINE).
Key findings:
Treatment failure in HLA DQA1*O5: A trend toward increasedtreatment failure amongHLA DQA1*05-positive participantswas not statistically-significant (hazard ratio 1.58; P = 0.08).
HLA DQA1*05 and Treatment Failure Rate: During the followup period, HLA DQA1*05-positive patients had a 35% failure rate compared to 26% for those who were HLA DQA1*05-negative (P=0.098). The overall failure rate was 30%
Methotrexate Combined with HLA DQA1*05Effect: Patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005).
Anti-TNF Medication Comparison: Treatment failure was similar between infliximab and adalimumab, 29% and 33% respectively
Antidrug antibodies (ADA): A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, P = 0.09). The addition of methotrexate to the treatment regimen mitigated the risk of treatment failure among individuals positive for HLA DQA1*05 and reduced the odds of developing ADA by 90%.
Rate of ADA: “After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12; P = 0.008).”
Discussion Points:
“A retrospective by Fuentes-Valenzuela et al …found that if patients underwent proactive TDM, there was no increase in the rate of treatment discontinuation among those who were HLA DQ-A105 positive compared with HLA DQ-A105 negative”
“The totality of evidence suggests that HLA DQ-A1*05 seems to confer a risk of both immunogenicity and treatment failure, particularly among infliximab-treated patients. Furthermore, this risk may be mitigated by the use of proactive TDM and/or concomitant immunomodulators.”
My take (borrowed in part from authors): “40% of patients were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate.” The use of combination therapy (methotrexate with anti-TNF) was associated with the lowest failure rates.
Methods: This post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in the following studies: phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials. It was noted that there were 1021 patients in U-EXCEL and U-EXCEED; 143 (14.0%) had any fistulas at baseline (66 draining). Most (n = 128) had perianal fistulas (56 draining).
Key findings:
Fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo
These slides from Figure 1 show the resolution of drainage in perianal draining fistulas, closure of external perianal fistula openings, and closure of external openings for any fistula at week 12 of the induction trials and week 52 of the maintenance trial.
Discussion points:
Patients with draining fistulas often experience higher disease burden
Most patients in U-EXCEL and U-EXCEED had failed at least 2 prior biologic treatments (which often included anti-TNF therapy), reflecting a more refractory and difficult-to-treat population in CD
Despite the presence of perianal disease, patients with fistulizing CD treated with upadacitinib showed concurrent improvements in CD symptoms (CDAI, SF, and APS), luminal disease (endoscopic response and SES-CD), and markers of inflammation
My take: This study shows that upadacitinib is more effective than placebo; however, the majority of patients continued with ongoing perianal disease.
This case report of four patients provides a good review of metastatic Crohn’s disease (MCD). MCD indicates that there is noncontiguous dermatological spread of CD involving the genitalia and perineum.
Key points:
“Less than 100 cases of pediatric MCD have been reported in the literature to date. These lesions are characterized by swelling, plaques, nodules, fissures, ulcerations, or crusts. In children, MCD typically presents as genital swelling with or without erythema in approximately 85% of cases.”
“Prior studies have shown that MCD co-occurs with CD in 50.8% of children, while others may develop GI symptoms after MCD diagnosis (15.3%) or even lack signs of CD (11.9%).”
“Scrotal histopathology revealed granulomatous inflammation, and genetic testing identified pathogenic variants in NOD2, COL7A1, and Chek2, as well as additional variants of uncertain significance.”
The optimal treatment is not clear. “Prior case reports and case series have shown positive responses to TNF-α inhibitors, but relapses may be common. Similarly, only partial improvement was noted in our patients treated with infliximab and adalimumab.”
Discussion: “Many patients do not demonstrate GI symptoms and may experience significant delays in diagnosis.”
My take: This article provides a good review of metastatic Crohn’s disease which is a rare problem. I have had two patients with this disorder. This problem fits the adage of “the more you see, the more you know; and, the more you know, the more you see.”
This was a cross-sectional study of newly diagnosed pediatric patients (n=869) with IBD at 22 United States sites from 2019 to 2022. 57% were diagnosed with CD, 34% with UC, and 4% with IBD-U.
Key findings:
Overall, the mean time from symptom onset to diagnosis was 265.9 days
Factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6), and longer travel time to clinic (>1 hour [OR, 1.7], >2 hours [OR, 1.8] each vs <30 minutes)
There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust
The finding that there is a longer diagnostic delay with CD than UC is consistent with prior studies. The longer travel time has not been widely recognized as a factor associated with delayed diagnosis, though it has been associated with other negative outcomes like higher mortality with chronic liver disease.
Regarding the lack of a negative impact from factors like race/ethnicity and income, my suspicion is that this is probably related to several factors:
Overall, the pediatric age group has a very high rate of being insured as most children without commercial insurance currently qualify for Medicaid. This helps improve access to needed/timely health care
B Kaj‐Carbaidwala et al. J Pediatr Gastroenterol Nutr. 2025; 80:450–454. Determining the time to cholangiocarcinoma in pediatric‐onset PSC‐IBD
Background: “Cholangiocarcinoma is a devastating disease, with up to 80% mortality and limited treatment options…A large retrospective cohort study reported that cholangiocarcinoma occurred in 1000 per 100,000 (1%) of children with PSC, with all occurring in children over 15 years of age and at a median of 6 years after the PSC diagnosis…Primary sclerosing cholangitis (PSC) is associated with a 400× increased risk of cholangiocarcinoma.”
Methods: Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric‐onset PSC‐IBD‐cholangiocarcinoma
Key findings:
The earliest diagnosis of cholangiocarcinoma was made at 14 years of age.
14% of of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 6 months of the second diagnosis
23% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first year of the second diagnosis
38% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 2 years.
50% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 7 years
50% of patients were between 14 and 25 years old when diagnosed with cholangiocarcinoma
Based on these data, the authors recommend screening for cholangiocarcinoma in this population of pediatric patients with IBD-PSC. Screening would include ultrasound or magnetic resonance cholangiopancreatography along with serum cancer antigen 19‐9 screening every 6–12 months. At the same time, the authors acknowledge limitations including a highly-selected patient population (selection bias) and relatively small number of patients. The absolute increase in risk for cholangiocarcinoma is not known. This study did not provide an estimate of the number of patients with IBD-PSC who develop cholangiocarcinoma; it only provides data on those with cholangiocarcinoma (thus no denominator to establish risk).
My take: Children, particularly adolescents, with IBD-PSC are at increased risk for both cholangiocarcinoma and colorectal cancer. The optimal surveillance strategy is still unclear. However, particularly in adolescents, I would favor yearly ultrasound and CA 19-9 for cholangiocarcinoma along with a low threshold for frequent colonoscopy (see ESPGHAN guidelines below).
In the news: AP 5/4/25: Cuts have eliminated more than a dozen US government health-tracking programs “U.S. Health Secretary Robert F. Kennedy Jr.’s motto is “ Make America Healthy Again,” but government cuts could make it harder to know if that’s happening…..Among those terminated at the Centers for Disease Control and Prevention were experts tracking abortions, pregnancies, job-related injuries, lead poisonings, sexual violence and youth smoking, the AP found.”
Anantara Resort, Mai Khao Phuket
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Methods: This was a “real-world practice” retrospective study (2017-2022) with 11,992 adult patients who were newly initiating a biologic therapy for UC/CD. 1,293 patients underwent a biologic switch, 64.2% of which were considered an overlapping switch (OS).
Key findings:
Adjusted incidence ratio IR) per 1,000 person years, for any infection, were comparable across switching groups. No significant differences in aHR of infections were found between OS and NOS [any infection aHR: 1.40, P=.17; serious infection aHR: 0.95, P=.93].
My take (borrowed from authors): “Overlapping switches were common and not associated with an increased risk of serious infection versus non-overlapping biologics.” Thus, shortened washout periods appear to pose minimal safety risks to patients while improving UC/CD therapy management.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition..
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