Prior Exposure to TNF Antagonists May Increase Response to JAK Inhibitors in Patients with Ulcerative Colitis

Posted on October 30, 2025 by gutsandgrowth

HH Lee et al. Clinical Gastroenterology and Hepatology 2025; 23, 2102 – 2114. Open Access! Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Methods: Meta-analysis of 17 randomized controlled trials in 8871 adults with moderate-severe UC. The authors calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist–naïve vs TNF antagonist–exposed patients.

Key findings:

JAK inhibitors: Less efficacious in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 0.47)
IL-23 antagonists: No significant difference was observed in efficacy of selective interleukin-23 antagonists vs placebo in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 1.07)
Lymphocyte trafficking inhibitors: More efficacious in TNF antagonist–naïve vs exposed patients (5 trials; odds ratio [OR], 1.88)

Discussion:

This study “confirmed prior observations that exposure to TNF antagonists significantly reduces the efficacy of lymphocyte trafficking inhibitors in inducing remission, including both vedolizumab and S1P receptor modulators, by approximately 50%.In contrast, prior exposure to TNF antagonists was associated with a significant increase in the efficacy of JAK inhibitors in inducing remission, with 2-fold higher efficacy in TNF antagonist–exposed vs TNF antagonist–naïve patients”
In the SELECT-COMPARE trial in patients with rheumatoid arthritis, there was also an improved response to upadacitinib in patients with prior adalimumab.
“The current findings raise the intriguing possibility that exposure to TNF antagonists could result in lasting effects on the immune system that differentially alter responsiveness to therapies with distinct mechanisms of action”

My take: This study suggests that JAK inhibitors are a good choice for secondary therapy after anti-TNF agents. Other factors, besides efficacy, including safety, extraintestinal manifestations, and cost, have to be considered as well.

Related blog posts:

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.

Comprehensive ACG Clinical Guidelines for Ulcerative Coliits (2025)

Posted on October 28, 2025 by gutsandgrowth

D Rubin et al. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. Open Access! ACG Clinical Guideline Update: Ulcerative Colitis in Adults

Today and tomorrow 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.

Table 2 in the UC guideline makes 54 recommendations and Table 3 provides 57 key concepts.

Selected Management Recommendations:

Table 2, #4: We recommend treating patients with UC to achieve endoscopic improvement (Mayo score 0 or 1) to increase the likelihood of sustained steroid-free remission and to prevent hospitalization and surgery
Table 2, #5: We recommend the use of FC (fecal calprotectin) in UC to assess response to therapy, to evaluate suspected relapse, and during maintenance
Table 2, #33: When infliximab is used as induction therapy for patients with moderately to severely active UC, we recommend combination therapy with a thiopurine
Table 2, #43: Recommend continuing tofacitinib or upadacitinib as compared with no treatment for maintenance of remission in patients with prior moderately to severely active UC now in remission after induction with tofacitinib or upadacitinib. **The authors recommend continuing each biologic that achieved remission with induction therapy (#38-#43)
Table 2, #51: In patients with ASUC failing to adequately respond to intravenous corticosteroids (IVCS) by 3 days, we recommend medical rescue therapy with infliximab or cyclosporine (Strong recommendation, moderate quality of evidence).

Key concepts:

Table 3, #29: Patients who are primary nonresponders to an anti-TNF (defined as lack of therapeutic benefit after induction and despite sufficient serum drug concentrations) should be evaluated and considered for alternative mechanisms of disease control (e.g., in a different class of therapy) rather than cycling to another drug within the anti-TNF class.
Table 3, #31: Subcutaneous infliximab and vedolizumab are considered equivalent to the standard intravenous maintenance dosing of these agents. The equivalence of the subcutaneous formulations for induction or as substitution for escalated doses of these therapies has not been robustly established.
Table 3, #41: Patients with UC should have available all medical options as recommended by their doctor and healthcare team. Third-party payers and requirements for step therapy should not come between the patient and their healthcare team in making decisions about treatment for UC.
Table 3, #48: All patients with ASUC should undergo a flexible sigmoidoscopy within 72 hours and preferably within 24 hours of admission. This should be used to assess endoscopic severity of inflammation and to obtain biopsies to evaluate for cytomegalovirus (CMV) colitis.
Table 3, #51: Nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, and medications with anticholinergic side effects should be avoided in ASUC.
Table 3, #57: In patients with ASUC initiating infliximab, dose intensification should be considered for those patients with low serum albumin (<2.5 g/dL).

My take: This article does an excellent job of summarizing current available evidence and good practice. Many of the recommendations may be helpful in garnering approval from third party payers.

Related blog posts:

NASPGHAN Pediatric Position Paper for Therapeutic Drug Monitoring

Posted on October 14, 2025 by gutsandgrowth

LM Felipez et al. J Pediatr Gastroenterol Nutr. 2025;81:1100–1117. Open Access! North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition position paper on the therapeutic drug monitoring in pediatric inflammatory bowel disease

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 6^133, 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.

Related blog posts:

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.

“Tasty & Healthy” Whole Food Diet For Crohn’s Disease

Posted on October 9, 2025 by gutsandgrowth

Y Frutkoff et al. Gastroenterology 2025 (Article in Press). Open Access! Whole Food Diet Induces Remission in Children and Young Adults With Mild to Moderate Crohn’s Disease and Is More Tolerable Than Exclusive Enteral Nutrition: A Randomized Controlled Trial

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.

Related blog posts:

JAKne: JAK inhibitor–induced acne

Posted on August 5, 2025 by gutsandgrowth

S Honap et al. Clinical Gastroenterology and Hepatology 2025 (EPUB). Open Access! Janus Kinase (JAK) Inhibitor-Induced Acne in Inflammatory Bowel Disease: An International, Multicenter, Retrospective Cohort Study

Mehtods: This international, multicenter, retrospective cohort study consecutively enrolled JAK-inhibitor-treated patients with IBD who subsequently developed acne (aka JAKne).

Key findings:

Among 2183 JAK inhibitor–treated patients with IBD, 272 developed acne
70% of acne cases occurred within the first 3 months of treatment initiation
The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib
Most cases were mild-moderate in severity. Mild (<10% of body surface area) was noted in 68%, Moderate (10-30% of BSA) was noted in 24%, and Severe (>30% of BSA) was note in 8%
Among those who developed acne, areas that were affected included the face in 89%, the back in 33%, the chest in 27% and the scalp in 1%
40% received pharmacologic intervention
18% of patients who developed acne had JAK inhibitor dose reduction or discontinuation

My take: JAKne is a common adverse effect. Early identification, proactive counseling, and timely interventions, such as dose reduction, acne therapies or referral to dermatology, are crucial in managing this side effect.

Related blog posts:

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.

Chronic Nonbacterial Osteomyelitis (CNO): What a GI Doctor Should Know

Posted on August 4, 2025 by gutsandgrowth

L Lim et al. The Journal of Pediatrics, Volume 283, 114636. Open Access! Chronic Nonbacterial Osteomyelitis: A Noninfectious Autoinflammatory Disorder of Bone

Prior to this review, I was familiar with the term chronic recurrent multifocal osteomyelitis (CRMO) but not CNO. CRMO is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions (DY Zhao et al. J Transl Autoimmun 2021; 4:100095. Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO)).

In this useful review, it is noted that IBD was associated with ~9% of cases of chronic nonbacterial osteomyelitis (CNO).

Key points:

“IBD identified before, during, or after CNO diagnosis, has been well-reported as an associated condition.^34-37 A review of cases of CNO with IBD showed that the diagnosis of CNO preceded the diagnosis of IBD in over half of the reported cases.³⁸“
“Children with CNO frequently experience a high burden of pain and impaired physical function. CNO can cause permanent deformities in any bone, but especially if there is spinal involvement and diagnosis and treatment are delayed”
“Bone biopsies should be performed if there is clinical suspicion of infection or malignancy, although tissue usually is not needed for diagnosis unless the clinical presentation is atypical”
“MRI is now the standard imaging test that usually starts with targeted examination of the affected area…A whole-body MRI (WB-MRI) should be considered for all patients with CNO at diagnosis when possible, as it may help support a diagnosis of CNO by detecting additional sites of bone inflammation that may be clinically inapparent, particularly vertebral lesions”
“Non-steroidal anti-inflammatory drugs (NSAIDs) are usually first-line treatment for children with CNO, except for those with vertebral lesions, who require systemic treatment… over half of children treated with NSAIDs experience a disease flare within the first 2 years,¹⁴ requiring either retreatment with NSAIDs or another systemic medication”
“In the presence of vertebral CNO lesions, or after failing NSAID monotherapy, three categories of systemic treatments are recommended by the Childhood Arthritis and Rheumatology Research Alliance (CARRA)⁵⁶: 1) synthetic DMARDs, 2) bisphosphonates, or 3) tumor necrosis factor-inhibitor (TNFi) biologic agents with or without methotrexate (to prevent the development of antibodies to the drug)”
“In practice, TNFi tends to be used more if children also have comorbid conditions for which TNFi already is indicated such as inflammatory arthritis and sacroiliitis,⁷ IBD,⁴^,⁷² and psoriasis.⁴^,¹⁴^,²⁴ “

My take: Being familiar with CNO is important for GI physicians as it can occur (rarely) in our patients with IBD. Another important caveat, which is not discussed in this review, is that CNO can occur paradoxically due to the use of TNFi treatment.

Related blog posts:

The London Eye. This view makes it look a lot like a bicycle wheel.

Sulfasalazine vs 5-ASA: Treatment Outcomes in Pediatric UC

Posted on July 9, 2025 by gutsandgrowth

I Mansuri et al. J Pediatr Gastroenterol Nutr. 2025;80:988–997. Clinical outcomes of maintenance therapy with sulfasalazine compared to 5-aminosalicylates in children with ulcerative colitis

Methods: This was a retrospective review of children diagnosed with UC between June 1999 and December 2019 at Boston Children’s Hospital. 124 started on sulfasalazine (SZ) and 309 on 5-aminosalicylates (5-ASA). Most patients had mild to moderate disease based on PUCAI score; ~12% had severe disease.

Key findings:

At 1 year, 54%, 44.3%, and 36.6% of patients on SZ, 5-ASA, and those who switched, respectively, were in steroid-free remission (p = 0.13)
All medication switches due to adverse reactions (24) were from SZ to 5-ASA. No patient was switched from 5-ASA to SZ because of adverse reactions. The non-severe adverse reactions noted were nausea, vomiting, abdominal pain, non-severe skin rash, headache, mild leucopenia, and lymphadenitis. Three patients had serious skin reactions, and one had pancreatitis.
SZ tended to have more minor adverse reactions. Except for countering adverse reactions, switching between SZ and 5-ASA did not offer therapeutic benefits. Disease severity at diagnosis predicted early treatment escalation

Discussion Points:

SZ offers advantages such as lower cost and availability in suspension form; the suspension form is particularly beneficial for young children and those unable to swallow the solid form of medication.
5-ASA formulations can be almost 10–50 times more expensive than SZ. For example, the wholesale acquisition cost of monthly generic SZ is $30 compared to $274 for generic Lialda, $1131 for generic Pentasa, and $1890 for generic Asacol HD

My take: About 20% of patients had to switch from Sz to 5-ASA due to adverse reactions; though, Sz had a mildly higher response rate (not statistically-significant). Switching between SZ and 5-ASA or vice versa is unlikely to provide much therapeutic benefit; patients who switched agents for medical reasons (rather than reactions) were more likely to require escalation to either a biologic or immune modulator.

Related blog posts:

The VEO-IBD Foundation -Developing Resource for Families

Posted on June 30, 2025 by gutsandgrowth

Link: Family reflections: research gives back childhood: a family’s experience with very early onset inflammatory bowel disease Pediatric Research; https://doi.org/10.1038/s41390-024-03506-8

An excerpt:

Very Early Onset Inflammatory Bowel Disease is so rare and individualized that no standard of care yet exists, and almost none of the interventions are approved for infants. After eliminating all dairy, prematurely ending breastfeeding, and moving exclusively to a prescription formula, we tried and failed multiple classes of medications, hoping each time that this medication would be the one that would ease our son’s suffering. Doctors are only now building a history of successful interventions to draw from, so treatment options come from very small studies from Very Early Onset Inflammatory Bowel Disease researchers and educated guesses. Treatment options generally ramp up in aggressiveness, which is hard enough for parents of a miserably sick infant to process and decide. Once these interventions fail, drug costs and insurance approval become major hurdles. This process of trial-and-error in treating Very Early Onset Inflammatory Bowel Disease patients is a nightmare. On a weekly or monthly basis, parents must make life-altering decisions with very little data for a patient too young to advocate for themselves.

Link: The VEO-IBD Foundation This foundation is still in its early stages, but anticipate it will be a resource for families with VEO-IBD.

Related blog posts:

Constipation Preceding a New Diagnosis of Inflammatory Bowel Disease

Posted on June 16, 2025 by gutsandgrowth

S Cenni et al. J Pediatr Gastroenterol Nutr. 2025;80:799–806. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease: A retrospective study

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.

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Set of Shucked! at The Fox Theater. Really enjoyed this ‘corny’ musical.

MMR Vaccination Safety in Immunocompromised Kids with IBD and Liver Transplant

Posted on June 13, 2025 by gutsandgrowth

A Keutler et al. Vaccine 2025; 59: 127288. Open Access! Safety and immunogenicity of the measles-mumps-rubella vaccine in immunocompromised children with inflammatory bowel disease, or after liver transplantation: An observational study

Background: “Measles is a highly contagious disease and, despite the availability of a safe and effective vaccine, remains still an important cause of childhood death worldwide [1,2]. The risk of severe illness in measles-naive individuals is particularly high in immunocompromised patients with inflammatory bowel disease (IBD) or after liver transplantation (LT) [3]…Ideally, vaccination with live attenuated vaccines (LAVVs) should be completed four weeks before organ transplantation or the initiation of immunosuppressive therapy (IST) to allow for the live vaccine’s incubation period and minimize the risk of vaccine-associated disease…LAVVs are considered contraindicated during IST due to safety concerns and limited experience.”

Methods: “In this prospective multicenter observational study (DRKS00014569) 22 children and adolescents with incomplete MMR vaccination status were identified… with stable immunosuppressive therapy in the last three months with no evidence of underlying disease activity…Sixteen patients were vaccinated against MMR, eleven after liver transplantation and five with inflammatory bowel disease. At the time of vaccination, four patients were receiving moderate (e.g., tacrolimus drug level below 5 ng/ml), eleven were receiving high-intensity immunosuppression (e.g. anti-tumor-necrosis factor agents, mycophenolate mofetil) and one child had previously discontinued immunosuppressive treatment.”

Immediately prior to the references, the authors provide a downloadable document detailing how they chose to categorize the degree of immunosuppression and their precise protocol, including immunologic pretesting and drug contraindications as noted below.

Key findings:

There were no serious adverse events or complications related to the vaccination
In children receiving immunosuppressive medications, the seroconversion rate for measles after the first MMR vaccination was 73.3 % (11/15) and after the second vaccination 80 % (12/15)

My take: In carefully-selected immunocompromised pediatric patients, the MMR vaccine may be safe. However, given the small numbers receiving vaccination in this study, the absolute safety is unclear. Even infrequent adverse effects would be problematic. This study’s protocol could be helpful for those considering vaccination in immunocompromised populations with a measles epidemic. For now, the most important approach is improving vaccination rates in those (especially family members) without contraindications.

Related blog posts: