Steroids are commonly used and misused for inflammatory bowel disease. This article reviews best practices, steroid formulations/dosing, and potential complications.
For moderate to severe ulcerative colitis (in adults), the authors recommend treatment with 40 mg of prednisone daily. Patients with ASUC (acute severe ulcerative colitis) should be treated with 60 mg of IV methylprednisolone for 3 to 5 days, after which rescue therapy should be initiated
Use of budesonide is recommended as an option for many clinical situations to minimize steroid adverse effects. These situations include mild-moderate UC failing to respond to mesalamine, ileal CD and older patients
Postoperative complications: “In the postoperative period, patients treated with CS had a higher risk of both infectious complications (aOR, 3.69; 95% CI, 1.24–10.97) and major infectious complications (aOR, 5.54; 95% CI, 1.12–27.26) [Abrerra et al].135 Subramanian pooled data from 7 studies showing that preoperative CS use is associated with increased postoperative complications (OR, 1.41; 95% CI, 1.07–1.87) as well as infectious complications.
The authors note that corticosteroids “remain widely available and are an effective short-term option for induction of remission in patients with active UC or inflammatory CD. However, their well-described and significant safety profile warrants proactive strategies to limit their use through non-systemic formulations, short-term exposures, steroid-sparing maintenance options, and most recently, complete steroid avoidance strategies.”
My take: Continuing steroids when they are not effective prior to potential surgery (eg. ASUC) remains a frequent problem. Sometimes, it is difficult to know it they are helping some.
In this “DIETOMICS” study with 56 children with mild-to-severe Crohn’s disease, after a 2 week exclusive enteral nutrition (EEN) diet, 30 patients were randomized to CDED and 26 to EEN.
Diet intervention: The CDED group followed 3 diet phases over 24 weeks: phase 1 (weeks 3–8) supplemented with 50% PEN; phase 2 (weeks 9–14) with 25% PEN, as described previously16; and phase 3 (weeks 15–24) with gradual introduction of more foods, including 1 and 2 free meals per week from weeks 15 and 18, respectively.17 Patients in EEN group received 8 weeks of EEN followed by gradual introduction of free diet with 25% PEN up to week 24.
Key findings:
This study with a relatively small number of enrolled patients had a lot of variables in dietary parameters. “An additional potential confounder in this study is the use of IMM therapy. Although both groups were recommended to initiate IMM therapy from weeks 4 to 5 to maintain remission, several CDED patients opted for monotherapy with CDED and preferred to delay medication initiation. Interestingly, 90% of patients on CDED without IMM therapy were in remission at week 14 and 100% were in remission at week 2” (possibly impacting decision not to use IMM).
My take: This study adds another piece of information to the puzzle on dietary therapy for Crohn’s disease. The authors note the following: “while CDED shows promise as a standalone therapy in some cases, in more severe cases it may be more appropriately as an adjuvant to top-down treatment with early anti-TNF.4 Recent research and guidelines advocate for a top-down approach (anti-TNF ± nutrition) for more severe disease, emphasizing the integration of anti-TNF therapy with nutrition.8,29 This approach is crucial during critical growth stages, as the conventional step-up method may lead to ineffective use of IMM with prolonged steroid exposure and growth issues.12“
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
This multicenter prospective study (n=253) examined efficacy of treatment in patients with proximal ileal disease using balloon-assisted enteroscopy (BAE). The recruited patients had a mean disease duration of 4 years. 52% were naive to biologic treatment at baseline.
Key findings:
At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations
At week 26, after treatment with anti-TNF therapy (n=103), ustekinumab (n=99) or vedolizumab (n=51), endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum
The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%)
After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). In contrast, there was no significant differences in hospitalization and surgery associated with endoscopic activity vs remission in the colon or terminal ileum.
Discussion: Residual “proximal ileal ulcerations … are associated with a poorer prognosis…Additionally, we confirmed that proximal ileal inflammation is less responsive to biologic therapies compared with colonic inflammation. Although the reasons for this disparity remain unclear”
My take: Balloon-assisted enteroscopy is not frequently used in the setting of inflammatory bowel disease, particularly in pediatrics. MRE is typically used to follow proximal small bowel disease, though it has less sensitivity for luminal mucosal disease.
Yesterday and Today I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.
Selected Management Recommendations:
Table 1, #3: We suggest against requiring failure of conventional therapy before initiation of advanced therapy for the management of CD
Table 1, #13: We recommend combination therapy of intravenous infliximab with immunomodulators (thiopurines) as compared with treatment with either immunomodulators alone or intravenous infliximab alone in patients with CD who are naive to those agents
Table 1, #33: In patients with high-risk CD, we recommend anti-TNF therapy to prevent postoperative endoscopic recurrence
Key Concepts:
Table 2, #9: Symptoms of CD do not correlate well with the presence of active inflammation and therefore should not be the sole guide for therapy. Objective evaluation by endoscopic or cross-sectional imaging should be undertaken periodically to avoid errors of under- or over-treatment.
Table 2, #14: The 10-year cumulative risk of major abdominal surgery in CD is 40%–55%, although recent studies performed in the biologic era suggest that the 10-year risk may have decreased to 30%. The 10-year risk of a second resection after the first is 35%, although again more recent studies suggest that this may have dropped to closer to 30%.
Table 2, #15: In CD, the 5-year rate of symptomatic postoperative recurrence is ∼50%.
Table 2, #29: Small bowel imaging should be performed as part of the initial diagnostic workup for patients with suspected CD.
Table 2, #31: Because of the absence of radiation exposure, magnetic resonance enterography should be used preferentially in young patients (younger than 35 years) and in patients in whom it is likely that serial exams will need to be performed.
Table 2, #38: Mucosal healing as determined by endoscopy is a goal of therapy. Scoring systems are available to measure the endoscopic disease activity and may be used to monitor response to therapy.
Table 2, #41: Antibiotics are not an effective treatment for luminal inflammatory CD and should not be used as a primary therapy.
My take: Given the rapid changes in available therapies, it would be optimal to make these collaborative guidelines (AGA, ACG, NASPGHAN) available online with frequent updates (similar to HCVguidelines.org).
In this single center retrospective study from Ireland, the authors examined 122 patients (93 with Crohn’s disease [CD], 18 with ulcerative colitis [UC], 1 with IBDU) who received infliximab and had prospectively-collected data. The earlier cohort 2018-2019 received 5 mg/kg/dose and the later group 10 mg/kg/dose. Both groups had proactive therapeutic drug monitoring (pTDM).
Key findings:
The 5 mg/kg group, compared to the 10 mg/kg group, was less likely to have target pre-third TLs (6% vs 80%, P < .001) with the stated goal of >/= 15 microgm/mL
Fewer patients in the 5 mg/kg than 10 mg/kg group had pre-fourth TLs ≥5 µg/mL (6/48 [12.5%] vs 28/50 [56%], P < .001; mean [SD] TL 3.5 [6.3] vs 10.0 [9.9], P < .001)
Concurrent immunomodulator therapy was more common in the 5 mg/kg group (43% compared to 24%)
80% of patients were still receiving infliximab at 1 year including 87% of patients with CD and 54% with UC
The higher dose group had a lower CRP at 1 year followup. 26% of patients receiving the lower dose had a CRP > 5 mg/L compared with 9% in the higher dose group.
Some other measures of long term outcome (eg. IFX durability, clinical remission) were slightly better but did not reach statistical significance (see below)
Discussion Points:
“Our data show higher rates of below-target infliximab levels during and after induction in the 5 mg/kg group. Higher rates of dose escalation in this group during the first year resulted in similar dosing regimens…Thus, the similar infliximab durability and clinical outcomes at 1-year follow-up reflect early-dose optimization leading to dose equalization between the 2 groups, rather than a lack of benefit to higher dosing regimens”
“Our data affirm that proactive TDM with pre-emptive dose escalation restores below-target infliximab TLs and sustains clinical response…Indeed, in our cohort, some patients with low IFX levels pre-third dose were given their fourth dose 6 weeks later, rather than the standard 8 weeks. Without proactive TDM results, our rate of suboptimal TLs pre-fourth and during maintenance therapy would have been higher in both groups”
“Rates of immunomodulator use in the 10 mg/kg group were lower than in the earlier cohort of 5 mg/kg, reflecting changes in clinical practice over time”
My take:
This study shows that 94% of pediatric patients did NOT achieve adequate levels of infliximab at the pre-third dose with “standard” therapy. This was true even with 43% of the lower dose cohort receiving combination therapy (which often helps improve pharmacokinetics)
Proactive therapeutic drug monitoring helped mitigate the clinical outcomes, especially in the lower dosed cohort
“Children with IBD treated with the historic standard dose of 5 mg/kg induction are at increased risk of pharmacokinetic treatment failure related to high rates of suboptimal TLs”
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.
Therapeutic Drug Targets Based on Condition, Medication and Time of Therapy:
Discussion Points:
Pediatric Dosing is Different: “Pediatric studies have also determined adult infliximab targets are insufficient…In a prospective pediatric study, Clarkston et al. found that a trough level of 29 μg/mL at 2 weeks is required to achieve both clinical and biologic response. Patients with lower trough levels had 13-fold greater odds of clinical nonresponse. Additionally, a trough of 18 μg/mL at 6 weeks was associated with improved response. Patients with lower trough levels had sixfold greater odds of clinical nonresponse. They also observed that patients who did not achieve a trough >5–7 μg/mL by 14 weeks of therapy had a 21-fold increase in the odds of clinical nonresponse.62“
Undetectable/very low anti-TNF levels: “If the serum level is extremely low or undetectable, then full re-induction is warranted in addition to dose escalation.”
Timing of TDM: “As a practice point, TDM is routinely recommended at the end of induction for most patients. We recommend obtaining TDM earlier during induction in at-risk populations, including younger age children, those with hypoalbuminemia, and those with increased inflammatory burden.”
Maintenance proactive TDM: “Based on prospective randomized trial evidence, we recommend proactive TDM during maintenance every 6–12 months…yearly proactive TDM was associated with 55% reduced risk of developing antidrug antibodies.26“
Increased Antidrug Antibodies with Lower Infliximab Dosing: “In the pivotal REFINE study on immunogenicity in pediatric IBD, Coleman et al. found that antibodies to infliximab were detected in 68% of patients in the cohort, and starting dose under 7.5 mg/kg was one of the strongest predictors of developing antidrug antibodies.4“
Higher Doses Prevent Antidrug Antibodies: “The best available evidence for preventing immunogenicity supports initiating therapy with infliximab doses greater than 8 mg/kg, and in the case of hypoalbuminemia, doses greater than 10 mg/kg. For children <40 kg, doses of 200 mg/m2 are more appropriate.”
Perianal fistulas: “Overall, there is less evidence to support adalimumab use over infliximab for treatment of perianal fistulas. It is possible that adalimumab may have lower efficacy for perianal fistula.105 However, it is unclear if this is inherent to adalimumab, or if it relates to less frequent TDM or less frequent dose escalation in practice.”
Vedolizumab: “In general, as with other biologic therapies, a higher serum vedolizumab concentration is associated with higher likelihood of treatment response…Multiple studies identified that in patients with IBD (either UC or CD) early trough levels at Week 2132 with a cut off of >23.2 μg/mL or Week 6133, 134 with a cut off of above 22–28 μg/mL or at Week 14135) above 16.55 μg/mL predicted a higher likelihood of sustained response over the first year. In regard to clinical remission one study identified that corticosteroid free, clinical and biochemical remission was correlated to higher trough vedolizumab concentration.136“
Vedolizumab in younger patients: “Children under 30 kg require vedolizumab doses of 200 mg/m2 or 10 mg/kg.”
My take: “This NASPGHAN position paper should also serve to document that high-dose therapy, especially guided by TDM, is evidence-based standard of care.” This article clearly establishes three key points:
“Intensive anti-TNF⍺ dosing strategies are not experimental. The initial doses of infliximab and adalimumab approved by the United States Food and Drug Administration (FDA) routinely lead to under-treatment, poor outcomes, and treatment discontinuation.60, 117 There is a rich, corroborated, and verified evidence-base to support the safety and efficacy of high-dose therapy anti-TNF⍺ therapy when clinically indicated, especially as supported by TDM.50, 62, 65, 100, 101, 103, 118“
Therapeutic drug monitoring is essential in the pediatric population to optimize drug levels, allow many patients to do well with monotherapy, and to help avoid development of antidrug antibodies.
The best available evidence supports TDM during induction of vedolizumab as well.
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.
Yesterday’s post (“A Practical Guide to Diet and IBD” (2025)) provided a summary of data on a multitude of diets for inflammatory bowel disease. Today’s post describes a study on a new diet, called the Tasty & Healthy diet.
Background: Tasty & Healthy (T&H) is a whole food diet for Crohn’s disease (CD) that excludes processed food, gluten, red meat, and dairy, without requiring formula or mandatory ingredients.
Tasty & Healthy (T&H) is an exclusive whole food diet, first published in a charity cookbook in 2014… The T&H diet was developed to reduce proinflammatory dietary exposures by excluding gluten, animal fat (ie, red meat and dairy, except for plain yogurt), as well as all processed food (anything that comes in a package except for those with 1 unprocessed ingredient.” (see details and supportive references in Supplementary Appendix 1).
Methods: TASTI-MM was a clinician-blinded, randomized controlled trial comparing tolerability and effectiveness of T&H (n=41) vs exclusive enteral nutrition (EEN, n=42). The intention to treat analysis included 83 patients (mean age 14.5 yrs, range 7-25 yrs).
Key findings:
88% tolerated T&H vs 52% for EEN. 59% of the patients in the EEN arm did not complete the 8-week follow-up period, compared with only 15% in the T&H arm
Calprotectin, C-reactive protein, and erythrocyte sedimentation rate decreased significantly in both groups, with no between-group differences
Symptomatic remission was achieved in 56% of the T&H group vs 38% of the EEN group
Calprotectin <250 μg/g was achieved in 34% T&H vs 33% of the EEN group
Microbiome α-diversity improved in the T&H arm and declined in the EEN arm, showing superior species richness at both week 4 and week 8. Species associated with bowel inflammation, such as Ruminococcus gnavus, decreased in T&H and increased in EEN (q < .001)
Discussion Points:
“In multiple studies CDED has been found to induce symptomatic remission in 62%–77% of patients with mild to moderate uncomplicated CD, including biologic remission in a subset of patients. Although conceptually similar to CDED in the exclusion of proinflammatory food groups, the T&H diet differs in structure—requiring no formula and no mandatory components, thus offering greater dietary flexibility.”
“The T&H diet was tested across multiple international centers, while still achieving similar outcomes compared with EEN. The use of any exclusion diet requires guidance of a dietitian to ensure balanced nutrition, and this becomes even more important in diets when formula is not needed. Other exclusive whole food diets studied in the RCT setting are the Specific Carbohydrate Diet and Mediterranean diet, which were effective in inducing symptomatic remission, but demonstrated insufficient biologic remission rates.”
“In the past, dietary interventions have not been as widely adopted in adults as in children…Although EEN use has been hampered by the thought that adults will not tolerate nutritional interventions, the advent of whole food diets has changed that notion…In this study, we found that not only were the included adults adherent to the T&H diet, it was as effective as in children and treatment response was not associated with age.”
Related article: Plotkin L, Aharoni Y, Fenster D, et al. Tasty & Healthy is a dietary approach for inducing and maintaining remission in Crohn’s disease: a prospective case series. United European Gastroenterol J 2021;9:521 (PO431).
My take: This “Tasty & Healthy” Diet appears to be an effective option for induction of remission for mild to moderate Crohn’s disease. Extended studies will be needed to help determine whether it could be used for longer duration in those with a response. Also, whoever labelled this diet initially clearly understands marketing as it sounds a lot better than EEN or CDED.
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: Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks
**This study presents data from the entire cohort (n=673); a previous report from ENDURE-3 analyzed data on 502 patients (though findings were nearly identical). EV Loftus et al. N Engl J Med 2023; 388:1966-1980 (Related post: Landmark Study: Oral Biologic for Crohn’s –Upadacitinib)
Key findings:
At week 52, more upadacitinib-treated vs placebo patients achieved CDAI clinical remission (upadacitinib 15 mg, 36.2% and upadacitinib 30 mg, 51.5% vs placebo, 15.2%)
The rates of endoscopic response were 27.3% for upadacitinib 15 mg and 40.7% for upadacitinib 30 mg vs 7.2% for placebo
Herpes zoster infections occurred more frequently in the upadacitinib groups compared with placebo; all were nonserious, and most involved a single dermatome
In U-ENDURE, no dose-dependent risk for MACE, VTE, or malignancy (excluding NMSC) was observed during the 52-week maintenance period
My take: Upadacitinib is a effective in a good number of patients with with moderately to severely active Crohn’s disease who have been refractory to other advanced therapies.
This recent commentary on the all-subcutaneous induction and maintenance treatment with guselkumab, an anti-IL23 agent, reviewed the GRAVITI study. Related post: Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study
However, what captured my attention was the last sentence: “The convenience of subcutaneous induction enhances patient friendliness, positioning guselkumab as a strong market contender. Could an oral anti–IL-23 formulation be the next game changer?14“
“Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC)…
In the ANTHEM-UC study (n=252), three doses of once daily icotrokinra were tested with all meeting the primary endpoint of clinical response at Week 12. A response rate of 63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus 27% for placebo (p<0.001). Further, 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01). Remission and response rates continued to improve through Week 28.
Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.”
My take: It would be terrific for patients with inflammatory bowel disease (and other immune-mediated diseases) to have another excellent oral therapy. A prior study of plaque psoriasis indicated that an oral IL-23 medication is feasible (Related post: In Trials: An Oral IL-23 Antagonist Peptide).
Related joke (regarding “caught my eye” in the title of this post):
A man who lived in a block of apartments thought it was raining and put his head out the window to check. As he did so a glass eye fell into his hand. He looked up to see where it came from in time to see a young woman looking down. “Is this yours?” he asked.
She said, “Yes, could you bring it up?” and the man agreed. On arrival she was profuse in her thanks and offered the man a drink. Shortly afterwards she said, “I’m about to have dinner. There’s plenty; would you like to join me?” He readily accepted her offer and both enjoyed a lovely meal. As the evening was drawing to a close the lady said, “I’ve had a marvelous evening. Would you like to stay the night?” The man hesitated then said, “Do you act like this with every man you meet?”
“No,” she replied, “only those who catch my eye.”
The Manneporte by Claude Monet (at the Metropolitan Museum of Art)
I was recently listening to a radio program (On Point) about the beneficial effects of sunlight.
The program notes that the potential beneficial effects of sunlight are much greater than the risks. Increased sunlight has been associated with lower rates of death, as well as lower rates of cardiovascular disease and autoimmune conditions like multiple sclerosis, type 1 diabetes, and Crohn’s disease.
When dermatologists recommend avoiding sunlight, they may be focused on the risks but not the benefits (though this varies among individuals). In addition, despite the more than 5-fold rise of melanoma diagnosis (especially in wealthy communities), there has not been a change in the rate of deaths due to melanoma. Skin cancers associated with sun exposure are mainly basal cell tumors and squamous cell tumors. These non-melanoma skin cancers have excellent survival rates.
Here is a link: The Healing Power of Sunlight (48 minutes) The most important part of this is in the middle, starting around 20 minutes.
My take: It’s a good idea to avoid sunburns but getting sunshine is good for health.
Related article:
Environ Epidemiol 2025. 9(3):e401. doi: 10.1097/EE9.0000000000000401. The association between time spent outdoors during daylight and mortality among participants of the Adventist Health Study 2 Cohort. Conclusion: “Moderate time outdoors in daylight during warmer months could be associated with lower risks of all-cause, CVD, and noncancer non-CVD mortality”
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