ENTERPRISE Study: Vedolizumab for Perianal Fistulizing Crohn’s Disease

DA Schwartz et al. Clin Gastroenterol Hepatol 2022; 20: 1059-1067. Open Access: Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease: ENTERPRISE Study

Methods: “Patients with moderately to severely active CD and 1–3 active perianal fistulae (identified on magnetic resonance imaging [MRI]) received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ + wk10)… Enrollment was stopped prematurely because of recruitment challenges”

Key findings:

  • “Rapid and sustained fistula closure was observed; 53.6% (VDZ, 64.3%; VDZ + wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ + wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30”
  • “MRI healing, defined as the disappearance of T2 hyperintensity signal and absence of gadolinium contrast enhancement,3 was not reached in this study…gadolinium contrast enhancement showed improvement at week 30…MRI studies have shown that internal fistulae healing lags behind clinical remission by a median of 12 months”
Figure 1
Figure 2 B

The study findings are limited by relatively small size and lack of control group (eg. placebo or seton/antibiotic group). However, the rate of response in this study is significantly higher than placebo studies which have shown “~1 in 6” who experienced fistula closure.

My take: Vedolizumab is another option for treating Crohn’s disease with perianal fistula. Both regimens in this study were associated with response, though the additional 10-week dose (in one group) did not improve outcomes.

Related blog posts:

Vedolizumab for Refractory Microscopic Colitis, Plus, Vedolizumab and Serious Infections

LC Shipley et al. Clin Gastroenterol Hepatol 2022; 20: 455-457. Vedolizumab Therapy in Refractory Microscopic Colitis: A Single Center Case Series

In this report, the authors describe nine patients with refractory microscopic colitis (median age 55 years) who were treated with vedolizumab.

Key findings:

  • Clinical response with induction in 9 (100%); time to >50% response ranged from 1 to 7 weeks with 5 patients responding within 2 weeks.
  • Sustained response with maintenance therapy in 6 (67%); duration of follow-up ranged from 1 month to 15 months. The three patients without response had symptom duration of 10 yrs, 12 yrs, and 25 yrs prior to institution of vedolizumab.
  • Only two patients had histologic follow-up. While both had clinical response, the patient with lymphocytic colitis had histologic resolution whereas a patient with collagenous colitis had histologic persistent.

My take: Given vedolizumab’s favorable safety profile, further studies (with endoscopic endpoints) of vedolizumab are needed to define its efficacy for microscopic colitis.

Another study with vedolizumab: J Kirchgesner et al. Clin Gastroenterol Hepatol 2022; 20: 314-324. Risk of Serious Infections With Vedolizumab Versus Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease

Key finding: The risk of serious infections was not different between vedolizumab and anti-TNF in the overall IBD cohort (HR, 0.95; 95% CI, 0·79-1.13), while the risk was decreased for vedolizumab users in patients with UC (HR, 0.68; 95% CI, 0.50-0.93), but not CD (HR, 1.10; 95% CI, 0.87-1.38)

Related blog post/related article:

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.

IBD Shorts: Fecal Calprotectin in UC & Medication Withdrawal, Outcome of Biosimilar Reverse Switches, Vedolizumab after Anti-TNF Therapy

TW Stevens et al. Inflamm Bowel Dis 2021; 19: 2333-2342. Open Access. Diagnostic Accuracy of Fecal Calprotectin Concentration in Evaluating Therapeutic Outcomes of Patients With Ulcerative Colitis

Key finding: A post hoc analysis of data from a phase 4 trial (the MOMENTUM trial) found that, even in patients (n=593 at week 8, n=305 at week 52) with complete endoscopic healing of UC, FC concentration can be used to discriminate patients with ongoing microscopic inflammation from patients with histologic remission.  The optimal FC cut-off concentrations for identification of patients with histologic remission were 75 μg/g at week 8 and 99 μg/g at week 52.

A Cassinotti et al. Clin Gastroenterol Hepatol 2021; 19: 2293-2301. Noninvasive Monitoring After Azathioprine Withdrawal in Patients With Inflammatory Bowel Disease in Deep Remission

Key finding: In this prospective study, 57 patients in deep remission stopped azathioprine after a median of 7 years. 26 (46%) relapsed within a median of 15 months. Fecal calprotectin (FC) levels were >50 mcg/g in all patients with relapse (FC specificity 100%) but the sensitivity was only 50%. Thus, having a normal FC does not preclude relapse but elevated FC is associated with relapse.

S Mahmmod et al. Inflamm Bowel Dis 2021; 27: 1954-1962. Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease

In this retrospective study, 75 patients, 9.9% of all patients, who had been changed from originator infliximab to a biosimilar had clinical worsening. Key finding: Improvement of reported symptoms was seen in 73.3% of patients after reverse switching back to originator infliximab; alsor 7 out of 9 patients (77.8%) with loss of response regained response

J Kim et al. Inflamm Bowel Dis 2021; 27: 1931-1941. Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study

Key finding: Clinical remission rates with vedolizumab among patients with CD (n=80) and patients with UC (n=78) were 44.1% and 44.0%. Among patients with UC, the endoscopic remission rate was 32.4%

Vedolizumab vs Adalimumab: Histology Outcomes from Varsity Trial

L Peyrin-Biroulet et al. Gastroenterol 2021; Open Access DOI:https://doi.org/10.1053/j.gastro.2021.06.015. Histologic Outcomes With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From An Efficacy and Safety Study of Vedolizumab Intravenous Compared to Adalimumab Subcutaneous in Participants With Ulcerative Colitis (VARSITY)

In total, 769 patients received vedolizumab (n = 383) or adalimumab (n = 386). Geboes Index and Robarts Histopathology Index (RHI) scores were used to assess prespecified histologic exploratory end points of histologic remission (Geboes <2 or RHI ≤2) and minimal histologic disease activity (Geboes ≤3.1 or RHI ≤4) at weeks 14 and 52.

Key findings:

Vedolizumab induced greater histologic remission than adalimumab:

  • week 14: Geboes: 16.7% vs 7.3%, RHI: 25.6% vs 16.1%
  • week 52: Geboes: 29.2% vs 8.3%, RHI: 37.6% vs 19.9%
  • Histologic outcomes were generally better in anti–TNF-naïve vs -failure patients

My take: This study shows that histologic outcomes with vedolizumab, similar to clinical outcomes, were better than with adalimumab. Some of this difference could be due to the trail design which did not allow optimization of adalimumab dosing.

Related posts:

Vedolizumab Exposure in Newborns

M Juulsgard et al. AP&T 2021: https://doi.org/10.1111/apt.16593. Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population-based cohort study

Key findings:

  • In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes
  • The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4)
  • No infant had detectable levels of vedolizumab at 6 months of age
  • Developmental milestones at 12 months were normal or above average
  • Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring

My take: Given the good safety profile of vedolizumab, this small study provides additional reassurance regarding use of vedolizumab during pregnancy.

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.

IBD Shorts: Tofacitinib Safety, Vit D post-op, EIM with Vedolizumab

P Deepak et al. Clin Gastroenterol Hepatol 2021; 19: 1592-1601. Full Text: Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis

This study described a ‘real-world’ experience with tofacitinib for Ulcerative Colitis in 260 adults; five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day).

Related blog posts -Tofacitinib:

JR de Bruyn et al. Clin Gastroenterol Hepatol 2021; 19: 1573-1582. Full Text: High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn’s Disease in a Randomized Placebo-Controlled Trial

Methods: Patients with CD after ileocolonic resection with ileocolonic anastomosis were assigned randomly to groups given weekly 25,000 IU oral vitamin D (n = 72) or placebo (n = 71) for 26 weeks, at 17 hospitals in The Netherlands and Belgium, from February 2014 through June 2017

Key finding: The cumulative rate of clinical recurrence did not differ significantly between the groups (18.1% in the vitamin D group vs 18.3% in the placebo group; P = .91). Though, the Vit D group achieved higher levels at week 26 (81 vs 43 of 25-OH Vit D)


GP Ramos et al. Inflamm Bowel Dis 2021; 27: 1270-1276. The Impact of Vedolizumab on Pre-Existing Extraintestinal Manifestations of Inflammatory Bowel Disease: A Multicenter Study

Key findings (n=201, retrospective study):

  • Worsening of EIMs after VDZ occurred in 34.8% of patients
  • Peripheral arthritis (PA) (68.2%) was most common EIM
  • Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients

Related blog post: Vedolizumab and Extraintestinal Manifestations of IBD

2021 AGA Guidelines For Crohn’s Disease

A series of articles details the 2021 AGA Guidelines for Crohn’s disease (CD) including a clinical practice guideline (pg 2496-2508), a clinical decision support tool (2509-2510), a spotlight summary (pg 2511), a technical review (2512-2557), and a review of the recommendations (pg 2557-2262). I will highlight the first article.

JD Feuerstein et al. Gastroenterol 2021; 160: 2496-2508. Full text: AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease

Full text: Spotlight

For me the most important of their recommendations was #7:

  • In adult outpatients with moderate to severe CD, the AGA suggests early introduction with a biologic with or without an immunomodulator rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.

Other points:

From Spotlight:

No Benefit of Combination Therapy with Ustekinumab or Vedolizumab

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

In a systematic review, key findings:

  • Combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68–1.05; I2=13.9%; Q test P = .17); n= 933 and n=2378 with combination therapy and monotherapy, respectively
  • Combination therapy was not associated with better clinical outcomes in patients receiving ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87–1.38; I2 = 11%; Q test P = .28); n=856 and n=1926 patients with combination therapy and monotherapy, respectively

Why don’t immunomodulators seem to help? “Unlike anti-TNF, prospective studies as well as post hoc analysis of randomized controlled trial consistently reported a low immunogenicity [with ustekinumab and vedolizumab]…all the prospective studies available to date have shown no impact of immunomodulator on the trough serum level of vedolizumab or ustekinumab.”

Limitation: patients treated with combination therapy in the included studies could be more severe

My take: “This meta-analysis found that overall the use of combination therapy in patients treated with vedolizumab or ustekinumab was not associated with a clinical benefit in comparison with the use of monotherapy.”

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Vedolizumab -Not Likely to Help Primary Sclerosing Cholangitis

A recent retrospective study (TJ Laborda et al. JPGN 2020; 71: 459-464 Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium) indicates that vedolizumab (VDZ) is unlikely to be helpful for primary sclerosing cholangits (PSC).

VDZ was initiated at median age of 16 years [IQR 15–18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis.

Key findings:

  • Overall, there was a mild increase in median GGT after initiation of VDZ. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response (defined as GGT <50 or at least a 75% decline) after 9 to 12 months
  • For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response

In the discussion, the authors note that their findings are in agreement with three retrospective studies in adults which have shown that VDZ is not effective for PSC in patients with IBD.

My take: This study indicates that VDZ is not likely to help with PSC, though 62% of IBD patients had improvement in their GI disease.

From The Onion

IBD Briefs -October 2020

EV Loftus et al.  AP&T  2020; 52: 1343-1365. Full text: Long‐term safety of vedolizumab for inflammatory bowel disease

GEMINI long‐term safety (LTS) study results –initiated 2009:

  • Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks. Total of 7999 patient years of vedolizumab exposure.
  • Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients.
  • There were no new trends for infections, malignancies, infusion‐related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy
  • Conclusion from authors: “The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns.”

Related blog posts:

AS Faye et al. Inflamm Bowel Dis 2020; 26: 1368-1376. Fertility Impact of Initial Operation Type for Female Ulcerative Colitis Patients (link includes video abstract)

Surgical options include Ileal pouch–anal anastomosis (IPAA), rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). Conclusions based on “a patient-level state transition microsimulation in TreeAge Pro:”… “Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20–30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar.”   In older age group, RCEI’s increase rate of childbirth (28%), decrease time to childbirth (14 months) and 77% reduction in IVF are important factors.

Related blog posts:

R Tariq et al. Inflamm Bowel Dis 2020; 26: 1415-1422. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease

In this retrospective study with 145 patients,  the overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. The authors concluded that “fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.”

Related blog posts:

Isle of Palms (July 2020)