Risk of gastrointestinal infections after initiating vedolizumab and anti-TNFα agents for ulcerative colitis

Retrospective cohort study

N= 805

To characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-TNFα agents for ulcerative colitis (UC)

Vedolizumab (n= 195)

Anti-TNFα agents (n= 610)

Adult, biologic-naïve patients with UC initiating vedolizumab, infliximab, or adalimumab at Brigham and Women’s Hospital, Massachusetts General Hospital, and affiliated hospitals

Patients with Crohn's disease, indeterminate colitis, prior colectomy or biologic exposure, and initiation of biologics for non-UC indications

Retrospective review of electronic health records and outside hospital records. CDI defined by positive stool C. difficile toxin or PCR assay with associated treatment. CMVC defined by characteristic CMV viral inclusions or positive immunohistochemical staining on colon histopathology followed by antiviral therapy. IPTW Cox regression used to assess hazard of CDI by biologic group.

Between June 1, 2014, and December 31, 2020

Primary: First CDI or CMVC after biologic initiation

Secondary: Severe CDI (>10,000 WBC or serum creatinine >1.5 mg/dL), CDI hospitalization, colectomy, or death within 30 days after CDI diagnosis

Vedolizumab (n= 195)

48 (31-64)

108 (55.4%)

Race

White, non-Hispanic

Hispanic

Black, non-Hispanic

Asian

Native American or Hawaiian

177 (90.8%)

5 (2.6%)

5 (2.6%)

4 (2.1%)

1 (0.5%)

529 (86.7%)

16 (2.6%)

21 (3.4%)

21 (3.4%)

1 (0.2%)

7 (2-18)

587 (254-956)

Current immunomodulator

Thiopurine

Methotrexate

18 (9.2%)

5 (2.6%) 

95 (15.6%)

8 (1.3%)

Curent corticosteroids

Systemic (prednisone or methylprednisolone)

Oral budesonide

Corticosteroid enemas only

84 (43.1%) 

26 (13.3%)

8 (4.1%) 

430 (70.5%)

62 (10.2%)

14 (2.3%)

Mayo endoscopic subscore* 

0 (normal mucosa)

1 (mild inflammation) 

2 (moderate inflammation)

3 (severe inflammation)

12 (6.2%)

47 (24.4%) 

95 (49.2%)

39 (20.2%)

20 (3.3%)

94 (15.7%)

289 (48.2%)

197 (32.8%)

13.8%

31.3%

0 (0.0%)

Abbreviations: IQR= interquartile range

*Data available only for 193 patients in the vedolizumab group and 600 patients in the anti-TNFα group

Endpoint

5.6

2.8

0

0

No significant differences in CDI-associated colectomies or deaths. CMVC was not observed after initiating vedolizumab. All CMVC cases occurred in the anti-TNFα group, often in the setting of hospitalization and corticosteroid use.

There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when considering the risk of gastrointestinal infections.

In the CMV analysis, the investigators were unable to obtain baseline CMV serologic data, preventing them from distinguishing between CMV reactivation and primary infection in the five identified cases. The small sample size also limited statistical comparisons and subgroup analyses. Additionally, the study did not adjust for corticosteroid and antibiotic exposures as time-varying covariates, which could affect the results. 

Resolution of CMV Infection in the Bowel on Vedolizumab Therapy

Design

Case presentation

An 18-year-old girl with a 3-year history of steroid-dependent extensive ulcerative colitis (UC) and thiopurine S-methyltransferase (TMPT) deficiency developed a severe exacerbation following the cessation of budesonide MMX. She responded to systemic steroids, and during prednisone therapy (reduced to 15 mg per day), blood CMV PCR and biopsies from ulcers in both the sigmoid and rectum were taken, with the ulcers being covered by endoscopy. The blood CMV test was negative, and there were no contraindications to vedolizumab, so treatment was initiated. Histopathology results, available only after the second scheduled dose, revealed dense CMV infection. Despite this, since there was no worsening of the patient’s condition, vedolizumab was continued without antiviral treatment. Following induction therapy, the patient achieved clinical, biochemical, and endoscopic remission, with no evidence of CMV in the rectum.

Study Author Conclusions

We believe this is the first report on the course of CMV infection in the bowel on vedolizumab therapy. The efficacy of antiviral treatment in addition to anti-inflammatory treatment in active UC is unproven. On the other hand, infliximab or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC. In our study, an intense CMV infection in IHC was related to a higher colectomy rate, in contrast to no infection or mild infection, suggesting that CMV might be another feature of more severe colitis. Resolution of infection with vedolizumab treatment would represent a case acting in support of this hypothesis.

Cytomegalovirus Colitis in a Patient With Ulcerative Colitis on Vedolizumab Monotherapy

Design

Case presentation

A 44-year-old woman with a six-year history of ulcerative colitis (UC) presented with a one-week history of bloody diarrhea, abdominal pain, and a painful red skin rash over her lower extremities. She had been on vedolizumab 300 mg intravenous infusions every eight weeks. Examination revealed erythematous nodules on her lower extremities, and a biopsy confirmed chronic active colitis. Laboratory results showed anemia and elevated inflammatory markers. A colonoscopy revealed severe left-sided colitis, and cytomegalovirus (CMV) polymerase chain reaction (PCR) from a tissue biopsy was positive with a viral load of 66,750 IU/ml. She was treated with IV methylprednisolone and ganciclovir for CMV colitis, leading to resolution of her skin rash and improvement in bloody diarrhea. After three weeks, her symptoms completely resolved, and she was discharged on a maintenance dose of valganciclovir, with complete resolution of her bloody diarrhea upon follow-up. 

Study Author Conclusions

CMV infection should be considered in all complicated UC patients or patients with persistent colitis not responding to immunosuppressive medication. Though vedolizumab is considered a safe biologic, its potential for systemic effect should be further explored and should be considered as a possible risk factor for CMV colitis in UC.

Comment on: ‘Resolution of CMV Infection in the Bowel on Vedolizumab Therapy’ 

Design

Case presentation

A 21-year-old male with refractory ulcerative colitis (UC) experienced cytomegalovirus (CMV) reactivation during immunosuppressive treatment. The patient had a history of steroid dependency and an inadequate response to azathioprine and golimumab before failing infliximab despite dose optimization. At baseline, endoscopic evaluation revealed severe pancolitis (MAYO III), with histology confirming CMV colitis through immunohistochemistry (IHC) and quantitative PCR (qPCR). After discontinuing infliximab, ganciclovir (5 mg/kg) was initiated to manage CMV colitis. Within one week, IHC for CMV became negative, prompting the initiation of vedolizumab (VZ) alongside continued corticosteroids and ganciclovir. By the third week, clinical and endoscopic improvement permitted steroid tapering. Following four doses of VZ, the patient achieved clinical remission, although qPCR continued to detect low levels of CMV DNA in colonic tissue for up to four months post-therapy. It was concluded that concurrent induction therapy with VZ and antivirals appeared safe in this setting, as no adverse effects or worsening of CMV infection were observed. Persistent low-level CMV DNA replication in the inflamed mucosa was noted but did not correlate with clinical deterioration. However, at day 175, symptoms recurred despite VZ optimization to every four weeks, necessitating a three-stage restorative proctocolectomy. Histopathological examination of the resected tissue confirmed active inflammation but no evidence of CMV.

Study Author Conclusions