Tag Archives: Vedolizumab

PODIUM Study: Jak Inhibitors and Ustekinumab Outperformed Vedolizumab as a 2nd Line Agent for Ulcerative Colitis

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G Privitera et al. Clin Gastroenterol Hepatl 2026; 24: 2539-2550. Open Access! Ustekinumab and Janus Kinase Inhibitors Outperform Vedolizumab as Second-Line Therapy in Anti-Tumor Necrosis Factor-Experienced Patients With Ulcerative Colitis

Before reading this article, I had to research why it was called “The Podium Study.” The research directly stacks three competing second-line classes of advanced therapies against each other: vedolizumab, ustekinumab, and JAK inhibitors; this is similar to a sports podium (1st, 2nd, and 3rd place), as the ultimate clinical goal of the study was to “rank” which medication performed best in terms of efficacy and safety after a patient fails anti-TNFα therapy. Of historical interest, there was an older, unrelated PODIUM trial, which stood for Pentasa Once Daily in Ulcerative Colitis for Maintenance of Remission.

Methods: In this retrospective, multicenter European study, there were 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi) with a mean age of 43.9 ± 15.5 years.  JAKi included 114 with tofacitinib, 28 with upadacitinib, and 5 with filgotinib. Achievement of biochemical steroid-free clinical remission (SFCR) within 12 months was identified by having SFCR associated with biomarker normalization: FCP <250 μg/g or CRP <5 mg/L—if discordant, FCP was considered the reference biomarker.

Key findings:

  • Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of steroid-free clinical remission (SFCR) (aHR, 1.54 and aHR, 1.66, respectively) and biochemical SFCR (aHR, 2.26 and 3.37, respectively) at 12 months
  • The crude incidence rate of SFCR at 12 months was 65.3% for vedolizumab, 87.0% for ustekinumab, and 80.2% for JAKi.
  • From a safety standpoint, JAKi were associated with an approximately 4-fold increase in the incidence rate of treatment-related AEs—primarily infections—compared with both vedolizumab and ustekinumab.

Discussion Points:

“Optimal sequencing in UC after anti-TNF-α exposure remains an open issue, as direct comparisons are scarce. Overall, our findings are consistent with the network meta-analysis by Lasa et al, which reported superior efficacy of JAKi and ustekinumab compared with vedolizumab in inducing clinical remission and endoscopic improvement in anti-TNF-α-experienced patients.14 However, these conclusions derive from indirect comparisons across heterogeneous randomized trials.”

My take: Vedolizumab is a good choice as a 1st line agent for ulcerative colitis but has a lower success rate as a 2nd line agent. Also, this study likely underestimates the potential effectiveness of JAKi as most individuals received tofacitinib rather than upadacitinib.

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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.

Flawed Dual Therapy Study of Vedolizumab and Upadacitinib

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J Yao et al. Clinical Gastroenterology and Hepatology, 2026. Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A Multicenter, Randomized Controlled Trial

Many patients do not respond to current advanced therapies which have prompted evaluation of dual therapy regimens. In this randomized open-label trial, the authors compared upadacitinib-vedolizumab dual therapy against vedolizumab monotherapy (40 combination, 73 monotherapy) for moderate-to-severe ulcerative colitis. Upadacitinib was dosed at 45 mg per day.

Key findings:

  • Endoscopic remission at week 8 was achieved by 37.5% in the dual therapy group compared to 15.1% with vedolizumab monotherapy (adjusted odds ratio, 3.34, 1.34–8.58; P = .010)
  • Clinical remission (65.0% vs 35.6%; P = .002) was significantly higher with combination therapy.
  • Adverse event rates were comparable (7.5% vs 6.8%), with no serious adverse events.

It is great to see more dual therapy data . While I am a little reluctant to criticize this study, as I think this type or research is both important and difficult, this trial has a couple problems. First of all, vedolizumab monotherapy may take twice as long to become effective; as such, the results at week 8 in isolation provoke more questions than answers. In addition, at this time point, it is not clear if combination therapy would be more effective than upadacitinib monotherapy.

In their discussion, the authors state that “the 65.0% clinical remission rate at week 8 substantially exceeds rates reported in pivotal induction trials for either upadacitinib (up to 34%11,25) or vedolizumab (approximately 17%24) as monotherapy….. The absence of a upadacitinib monotherapy arm precludes formal assessment of synergy; however, the observed combination endoscopic remission rate (37.5%) exceeds published upadacitinib monotherapy rates for Mayo score = 0 (approximately 14%–18%),11 suggesting a benefit beyond that of upadacitinib monotherapy alone.” However, in a study (RS Dalal et al. Clin Gastroenterol Hepatol 2024; 22: 666-668) comparing monotherapy with upadacitinib versus ustekinumab, upadacitinib had a steroid-free clinical remission rate of 62.1 %, and an endoscopic remission 37.5%. These results are nearly identical to the results of the combination therapy group.

My take: This study shows that upadacitinib works quicker than vedolizumab for moderate-to severe UC. It does not prove that upadacitinib in combination with vedolizumab is more effective than upadacitinib monotherapy.

The anticipated followup data at 1 year will be helpful to determine whether the combination with vedolizumab impacts long-term effectiveness of upadacitinib monotherapy. It is unfortunate that an upadacitinib monotherapy arm was not included in this study.

Another useful study would be whether patients who respond to upadacitinib as an induction combination therapy with vedolizumab could transition to vedolizumab monotherapy. This would leverage upadacitinib’s rapid onset and if effective, allow long-term treatment with vedolizumab which is considered to have the most favorable long-term safety data.

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Safety Data Up to Seven Years with Vedolizumab

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E Louis et al. Clin Gastroenterol Hepatol 2026; 24: 1654-1665. Open Access! Long-Term Safety of Vedolizumab in Patients With Ulcerative Colitis/Crohn’s Disease: A Prospective Observational Study

Methods: This was a prospective, observational, multicenter cohort study in adult patients (n=5208) with UC or CD starting treatment with vedolizumab or other biologics. The primary safety outcome was serious infections compared between cohorts using a Cox proportional hazards model adjusted by propensity score. Clinical effectiveness was a secondary outcome. Mean follow-up duration was 37.4 months. The vedolizumab group had greater age, duration of disease, and concomitant medication use at baseline, indicating more advanced disease.

Key findings:

  • In patients with UC, the incidence rate per 100 person-years of serious infections was 5.5 (vedolizumab) and 7.0 (other biologic), with an adjusted hazard ratio of 0.89 (P = .38).
  • In patients with CD, corresponding findings were 7.9 (vedolizumab) and 6.5 (other biologic) with adjusted hazard ratio of 1.15 (P = .16).
  • Rates of clinical response and clinical remission were similar in patients treated with vedolizumab compared with other biologics for both UC and CD.
Time to treatment failure in (A) biologic-naïve. Treatment failure included discontinuation of biologic treatment, IBD nonsurgical hospitalization, primary IBD surgery, and corticosteroid initiation.
Time to treatment failure in (B) biologic-experienced CD patients. 

My take: This large prospective study showed no new safety signals with mean followup of more than 3 years. There were no new trends or changes of clinical importance for infections (serious and opportunistic infections, gastrointestinal infections, respiratory tract infections, other infections), malignancies, infusion-related reactions, hepatotoxicity, and pregnancies. No cases of PML were reported. Efficacy was similar between vedolizumab and other biologics.

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Comparative Safety of Advanced Therapies for Ulcerative Colitis

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D Ahuja et al. Am J Gastroenterol 2026;121:1192–1201. Comparative Safety of Advanced Therapies in Patients With Ulcerative Colitis: An Administrative Claims-Based Study

Methods: Using an administrative claims database (OptumLabs Data Warehouse) with a ‘real-world’ cohort, the authors identified 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months.

Key findings:

Overall, the risk of serious infections was higher with infliximab than with the other therapies. The incidence of VTE in patients with UC was very low and comparable across all advanced therapies, including JAK inhibitors. Also, the incidence of MACE in patients with UC was
very low and comparable across all advanced therapies, including anti-ILs and JAK inhibitors.

From the discussion: “In a recent network meta-analysis and corresponding clinical guidelines on the management of moderate-to-severe UC, upadacitinib was ranked as having the highest efficacy for induction ofremission compared with all other agents (2,14). However, safety concerns with JAK inhibitors were raised in the pivotal ORAL Surveillance trial (15). In this noninferiority trial, tofacitinib, particularly at higher doses, was associated with a higher risk of serious and opportunistic infections, VTE, and MACE, compared with TNF antagonistsi n patients with rheumatoid arthritis. Following this, the US Food and Drug Administration changed JAK inhibitors’ labeling across all indications, restricting its use in patients with previous failure or intolerance to TNF antagonists…the ORAL Surveillance trial focused on older patients aged 50 years or older with rheumatoid arthritis and at least one cardiovascular risk factor…

[In this study, the] lack of an apparent increase in the risk of JAK inhibitors compared with other medications may be related to superior disease control achieved with JAK inhibitors or reverse causality where patients at high risk of MACE and/or VTE events are not prescribed JAK inhibitors.”

My take: This study provides additional reassurance that newer advanced therapies have similar or better safety than infliximab.

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Comparing Vedolizumab in “Early” and “Late” Crohn’s Disease

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Lancet Gastroenterol Hepatol 2026; 11: 12-21. Vedolizumab in early and late Crohn’s disease (LOVE-CD): a phase 4 open-label cohort study

Methods: Eligible patients were adults aged 18–80 years with moderate to severe Crohn’s disease (Crohn’s Disease Activity Index [CDAI] 220–450, with ulcers at endoscopy). Patients were divided into two groups: those with early Crohn’s disease, n=86 (defined as a diagnosis less than 2 years ago and naive to advanced treatment [naive or only treated with corticosteroids or immunomodulators, or both]); and those with late Crohn’s disease, n=174 (defined as a diagnosis more than 2 years ago and previously treated with corticosteroids, immunomodulators, and anti-TNF agents). The primary endpoint was the proportion of patients with clinical and endoscopic remission (defined as CDAI ≤150 and SES-CD <4) at both week 26 and 52.

Key findings:

  • Clinical and endoscopic remission at both week 26 and 52 was achieved in 27 (31·4%) of 86 patients with early Crohn’s disease versus 15 (8·6%) of 174 patients with late Crohn’s disease (difference 22·8%, 95% CI 12·6–33·7)
  • Serious adverse events occurred in three (3·5%) of 86 patients with early Crohn’s disease versus 46 (26·4%) of 174 patients with late Crohn’s disease and included infections (one [1·2%] vs 13 [7·5%]), surgery (none vs eight [4·6%]), intestinal obstruction (none vs four [2·3%]), exacerbation of Crohn’s disease (one [1·2%] vs six [3·4%]), and malignancy (none vs three [1·7%])
Corticosteroidfree clinical remission at all timepoints

Discussion:

  • “After 52 weeks of open-label treatment, almost 60% of patients with early disease achieved clinical remission and more than 50% were in endoscopic remission. By contrast, deep remission rates at both weeks 26 and 52 were observed in less than 10% of patients with late Crohn’s disease (ie, those with longstanding disease and previous exposure to anti-TNF
    agents).”
  • “Despite the earlier stage at which vedolizumab was initiated, disease severity was comparable betweenthe early and late Crohn’s disease groups, from a clinical (median CDAI 255 vs 259), endoscopic (median SES-CD 9 vs 12), and biochemical perspective (median serum C-reactive protein 9 mg/L vs 8 mg/L).”
  • “A pivotal observation in LOVE-CD was that dose intensification after week 26 (ie, doubling the dose) in patients without an endoscopic response did not lead to higher endoscopic remission rates, despite significantly higher serum vedolizumab concentrations. This
    finding suggests that the dosing schedule that was originally designed and approved is optimal for most patients and saturates the target. Patients who do not respond most likely have other dominant immune pathways that are activated and remain unaffected by
    vedolizumab.”
  • “All three classes of biologics approved for the treatment of Crohn’s disease perform better when initiated early in the disease course.”

My take: For Crohn’s disease (CD), vedolizumab should be mainly used in those without prior biologic therapy. In addition, changes in vedolizumab dosing based on concentrations is much less helpful than it is with anti-TNF agents.

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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.

VedoKids Study: Vedolizumab for Extraintestinal Manifestations of Inflammatory Bowel Disease

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G D’Arcangelo et al. J Pediatr Gastroenterol Nutr. 2026;82:495–502. Open Access! Vedolizumab for extraintestinal manifestations in pediatric inflammatory bowel disease: Results from the VedoKids study

Background: “Since vedolizumab is a gut-selective anti-α4β7 integrin, its effect on EIMs has been a matter of debate, with relevant data lacking in pediatric IBD. A systematic review, which included three interventional studies, five non-interventional studies, and three case series, concluded that there is insufficient evidence supporting the efficacy of vedolizumab for treating pre-existing EIMs in adults.3“

Methods: This was a subgroup analysis of the pediatric VedoKids cohort, a multicenter, prospective “real-life” study of children (aged 0–18 years) with IBD treated with vedolizumab and followed through 54 weeks.

Key findings:

  • EIMs were identified in 18/142 (12.6%) children at baseline
  • Children with EIMs had an average age of diagnosis of 9 yrs compared to 12 yrs in those without EIMs
  • Children with EIMs had higher rate of pancolitis in UC and ileocolonic distribution in CD
  • Prior anti-TNF medication was noted in 16 (89%) of EIM cohort compared to 74 (60%) of non-EIM cohort
  • Concomitant medications were administered in 72% of EIM cases and to a similar number of non-EIM patients. For EIM patients, ASA were given in 7, steroids in 10, thiopurines in 4 and methotrexate in 2
  • Children with EIMs had more active disease (see below)
  • EIM resolution rate of 89%, mainly occurring within the early weeks of vedolizumab treatment

My take: While this study has several limitations, including the high rate of concomitant medications, it shows that most patients receiving vedolizumab had resolution of their EIMs. In addition, it shows that patients with EIMs had a more severe IBD phenotype.

Related blog posts:

NASPGHAN Pediatric Position Paper for Therapeutic Drug Monitoring

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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 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:

  1. “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“
  2. 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.
  3. The best available evidence supports TDM during induction of vedolizumab as well.

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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.

Comparing Infliximab, Adalimumab, and Vedolizumab in Adults and Children with Ulcerative Colitis

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O Atia et al. Infammatory Bowel Diseases, 2025, 31, 617–624. Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN

This was a nationwide Israeli study with 15,111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years. The dataset includes ~98% of the Israeli population; “the accuracy of medication data is high, as the Israeli health care system provides medications almost free of charge through the HMOs, and the electronic dispensing of drugs contributes to reliable and precise data.”

Key findings:

  • After 5 years of treatment, 43% of the patients with UC sustained their first biologic
  • The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively)
  • Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively) or combotherapy (78%/56% vs 91%/58%, respectively)
  • Durability of infliximab at 1 yr and 5 yrs was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; , P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%)
  • The durability rate was similar for vedolizumab monotherapy at 1 yr and 5 yrs (77%/56%) compared with adalimumab monotherapy (69%/52%), and infliximab monotherapy (73%/55% vs 62%/44%). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%), respectively;

My take: When looking at the durability plots, the three main biologics in this study, infliximab, adalimumab and vedolizumab, performed similarly. Whether therapeutic drug monitoring would influence theses results is not clear. It is interesting that a recent study in the pediatric population found that combination therapy was important for adalimumab and not infliximab (see: Why Do Children Taking Adalimumab Benefit from Methotrexate Dual Therapy?)

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Also, from AGA Today (3/20/25): FDA Approves Guselkumab To Treat Patients With Crohn’s Disease

HCPlive (3/20, Campbell) reports the FDA on Thursday announced the approval of “guselkumab (Tremfya) for the treatment of adults with moderately to severely active Crohn disease.” The announcement from Johnson and Johnson claims the “approval is based on data from multiple phase 3 trials, including the GALAXI trials, which found guselkumab outperformed ustekinumab (Stelara) for multiple endoscopic endpoints. The agent now boasts indications for moderately to severely active Crohn disease and moderately to severely active ulcerative colitis (UC).” This is the fourth indication for guselkumab in the US

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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.

Vedolizumab’s Impact on Postoperative Crohn’s Disease Recurrence

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G D’Haens et al. Lancet Gastroenterol Hepatol 2025; 10: 26-33. Vedolizumab to prevent postoperative recurrence of Crohn’s disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial

In the REPREVIO study,  a double-blind, randomized, placebo-controlled trial, 80 adults received either vedolizumab (300 mg IV) (n=43) or placebo (n=37) at weeks 0, 8, 16 and 24 following ileocolonic resection and had one or more risk factors for recurrence.

Key findings:

  • At week 26, the probability of a lower modified Rutgeerts score with vedolizumab versus placebo was 77·8% (95% CI 66·4 to 86·3; p<0·0001).
  • Severe endoscopic recurrence was observed in ten (23·3%) of 43 patients in the vedolizumab group versus 23 (62·2%) of 37 patients in the placebo group (difference –38·9% [95% CI –56·0 to –17·3]; p=0·0004). 
  • Adverse effects were noted in three patients who received vedolizumab (bilateral tubo-ovarian abscesses, thrombosed hemorrhoids, and pancreatic adenocarcinoma) and two patients who received placebo (intestinal perforation related to Crohn’s disease and severe abdominal pain)

My take: This study shows that vedolizumab is another biologic capable of reducing postoperative recurrence following ileocolonic resection in Crohn’s disease. Infliximab has been shown to reduce recurrence as well (shown in the PREVENT study).

Related blog posts:

Effects of Thiopurine Withdrawal in Randomized Trial of Vedolizumab-Treated Patients with Ulcerative Colitis

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A Pudipeddi et al. Clin Gastroenterol Hepatol 2024; 22: 2299-2308. Open Access! Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial

Methods: This was a multicenter randomized controlled trial recruited UC patients (n=62) on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine.

Key findings:

  •  At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 μg/mL versus 15.9 μg/mL, respectively, P = 0.36).
  • The continue group had significantly higher fecal calprotectin remission (calprotectin <150) (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Clinical and endoscopic remission favored the continue group though this did not reach statistical significance.
  • Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6–146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3–33.8; P = .03) predicted clinical relapse after thiopurine withdrawal.

Discussion: “In Australia, requirements are for UC patients to have failed at least 3 months of an immunomodulator before vedolizumab initiation. Consequently, UC patients are typically on combination therapy initially, and hence this study was designed as a withdrawal trial.” The authors note that previous studies have not shown superior outcomes with combination therapy (See blog post: No Benefit of Combination Therapy with Ustekinumab or Vedolizumab). “However, methodological flaws, heterogenous outcomes, and shorter durations of treatment limit these findings.”

My take (borrowed from authors): “Thiopurines might provide an incremental benefit to patients with UC using vedolizumab, … independent of vedolizumab pharmacokinetics.”

Related study: C Yzet et al. Clin Gastroenerol Hepatol 2021; 19: 668-679. Full Text: No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases: A Meta-analysis

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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.