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For medical professionals only
When conventional treatment of UC is ineffective, prompt application of vedelizumab can show efficacy
.
Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disorder of the colorectal mucosa that is divided into primary (first episode without past medical history) and chronic relapsing (recurrent symptoms during clinical remission) of unknown etiology, with mucus, bloody stools being the most common symptom, and can cause structural bowel injury, stenosis, and/or loss of function [1-2].
Mild UC can use aminosalicylic acid preparations as the main drug; Hospitalization is required in 20% of patients with moderate or severe disease, and treatment options include aminosalicylate, hormones, immunosuppressants, and/or biologic agents
.
Even if initial treatment is successful, patients with UC often require long-term maintenance therapy, and biological therapy is an important step [3].
Vedelizumab, an anti-α4β7 integrin, which selectively blocks lymphocyte transport to the intestine, is a first-line agent for the treatment of moderately to severely active UC and is indicated in patients who do not respond adequately or tolerate conventional therapy, significantly reduces the recurrence rate of UC, and has good safety and tolerability [4-6].
In this issue, we invite Tian Li, deputy chief physician of the Third Xiangya Hospital of Central South University, to share two classic cases of UC and explore the therapeutic effect
of vedelizumab on severe treatment-naïve UC and moderate chronic relapsing UC.
About the author
Tian Li Deputy Chief Physician
Deputy Director of the Department of Gastroenterology, Third Xiangya Hospital, Central South University
Doctor of Medicine, Deputy Chief Physician, Master Supervisor
Youth Committee Member of Digestive Endoscopy of Endoscopist Branch of Chinese Medical Doctor Association
Member of Digestive Endoscopy Committee of China Medical Education Association
Member of the Youth Club of the IBD Group of the Chinese Medical Association
Member of IBD Expert Committee of Beijing Medical Award Foundation
Vice Chairman of the Youth Committee of Digestive Endoscopy of Hunan Medical Association
Deputy Head and Secretary of the Ultrasound Endoscopy Group of Hunan Medical Association
Member and Secretary of Gastroenterologist Branch of Hunan Medical Association
Contributing reviewer for Gastrointestinal endoscopy
Classic case one
The patient, female, 40 years old, complained of "diarrhea and blood in the stool for more than 1 month"
.
History of present illness:
In April 2021, the patient began to have diarrhea without obvious triggers, about 3-8 times/day, mixed with dark red blood, with persistent swelling pain in the lower abdomen, which was tolerable
.
Colonoscopy at the local hospital on May 11, 2021: Sigmoid and rectal mucosal changes: infectious enteritis? (CMV infection to be expelled); IBD?; Disease examination: mucosa has erosion, interstitial mass lymphocytes, plasma cells infiltrate
.
After anti-infection, mesalazine 4g/d, regulation of intestinal flora and other treatments, the symptoms did not improve significantly, and he was transferred to our hospital for treatment
on May 20.
Admission Assessment:
Blood routine: WBC 6.
13×10 9/L, Hb 90g/L↓, Plt 187×109/L;C-reactive protein (CRP): 20.
04mg/L↑;ESR: 61mm/hr↑;
Fecal occult blood (OB): positive;
Calprotectin: 1800 ug/g↑;
Liver function: Alb 22.
6g/L↓;Connective tissue: positive for P-ANCA (+), positive for anti-SS-A antibody (++), positive for anti-U1-RNP/Sm antibody (+);
Cytomegalovirus (CMV) DNA: 1.
009×102cps/mL; Serum EBV-DNA: normal; Clostridium difficile test: negative
.
Colonoscopy: 30 cm from the anus, the colorectal mucosa is hyperemic and swollen, multiple deep chiseled ulcers of the sigmoid colon, diffuse superficial ulcers and erosions of the rectum, and purulent discharge (Figure 1).
Figure 1 Colonoscopy results of hospitalization
Pathology: (rectal) moderately active chronic inflammation, cryptitis and crypt abscess can be seen, interstitial plethocyte, plasma cell and eosinophil infiltration, (sigmoid colon) ulcer formation, focal macrokaryocytes, combined with immunohistochemistry consistent with cytomegalovirus infection
.
Admission diagnosis:
UC (E2, first-onset, severely active, Mayo score 11, CMV infection)
The treatment undergoes:
After admission, on June 1, 2021, vedelizumab 300mg intravenous drip, ganciclovir antiviral, anti-infection, regulation of intestinal flora, anticoagulation, nutritional support and other symptomatic supportive treatment were given, and the symptoms improved significantly on the third day after treatment, and the retest results on June 4, 2021 were as follows (Table 1):
Table 1 Comparison of indicators before and after initial treatment
The patient received vedelizumab 300mg intravenously on June 21, 2021, July 16, 2021, and September 7, 2021, and the results of the review after treatment were as follows (Table 2):
Table 2 Comparison of various indicators after four treatments
Colonoscopy was repeated on September 8, 2021: the scope was inserted to the end of the ileum, the mucosa at the end of the ileum was smooth, the ileocecal valve could be opened and closed, the mucosa around the appendix foramen was smooth, and the entire large intestine was scattered with pseudopolyps and white ulcer scars (Fig.
2).
Figure 2 Results of colonoscopy after treatment
Classic case two
The patient, a 31-year-old male, complained of "intermittent diarrhea and mucus and bloody stools for more than 4 years"
.
History of present illness:
The patient had diarrhea in November 2017 without obvious triggers, 7-8 times/day, watery stool and mushy stool alternately, and then mucus and bloody stool, accompanied by tenesmus and persistent tingling pain in the left lower abdomen, after being admitted to our hospital to complete the relevant examinations, it was diagnosed as UC (E3, primary type, moderate), and his symptoms improved after treatment with mesalazine 4g/d, and he was treated regularly with mesalazine after discharge, and still intermittently had diarrhea, mucus and bloody stools, and was admitted to our hospital on May 11, 2021 for treatment
。
Admission Assessment:
Blood routine: Hb 98g/L;
C-reactive protein (CRP): 20.
04mg/L;ESR: 56mm/hr;
The rest of the laboratory indicators are basically normal
.
Colonoscopy: scattered patchy erosions at the end of the ileum, shallow ulcers with a diameter of about 0.
3 cm, scattered patchy erosions and superficial ulcers in the sigmoid colon and rectum (Fig.
3).
Figure 3 Colonoscopy results
of hospitalization
Admission diagnosis:
UC (E3, chronic relapse, moderately active, Mayo score: 10)
Diagnosis and treatment:
From November 2017 to May 2021, mesalazine 4g/d + mesalazine suppository + five-flavor bitter ginseng capsules were used, during which symptoms recurred;
On May 11, May 25, 2021, and June 25, 2021, he received vedelizumab 300mg continuous intravenous drip, and the results after treatment were as follows (Table 3):
Table 3 Comparison of indicators before and after treatment
Repeat colonoscopy on 16 August 2021 (Figure 4):
Figure 4 Results of colonoscopy after treatment
The patient in case 1 was a treatment-naïve patient with severe UC complicated with CMV infection, the course of the disease was only more than 1 month, the conventional anti-infection, intestinal protection, and regulation of intestinal flora treatment were ineffective, and the symptoms were quickly controlled after treatment with vedelizumab, and then regular drug maintenance therapy achieved the effect of complete healing of the mucosa, and the CMV retest result was negative
.
The patient in case 2 is a chronic relapsed patient with moderate UC, the course of the disease is more than 4 years, the traditional regimen treatment can be temporarily effective, but the efficacy is not good, the symptoms are repeated, and the mucosal healing has not been obtained, and the treatment of vedelizumab has been upgraded, and clinical remission and complete mucosal healing
have been achieved after 3 courses of treatment.
Expert reviews
UC is a chronic, progressive disease of the colorectum that can occur at all ages and is increasing globally [7].
At present, the medical treatment methods of UC include the use of aminosalicylic acid, glucocorticoids, biological agents, etc.
, but the effect of aminosalicylic acid is limited, the safety of glucocorticoids is lacking, and TNF antagonists in biological agents are prone to serious infections in patients, and these treatment regimens cannot meet the needs of more attention to mucosal healing and disease prognosis in the management goals of UC in terms of efficacy and safety [8].
Therefore, both doctors and patients need safer and more effective treatment options
.
Biologics are one of the options for the treatment of ulcerative colitis, and vedelizumab has been approved in recent years for the treatment of moderate to severe UC.
Vedelizumab is a monoclonal antibody against integrin α4β7, which can selectively prevent white blood cells from penetrating into the submucosa of the gastrointestinal tract, thereby weakening the inflammatory response of the intestine, alleviating clinical symptoms such as diarrhea and abdominal pain, and promoting mucosal healing after long-term maintenance therapy, and does not significantly increase the risk of severe systemic opportunistic infections or other common complications, with a good safety profile [9-10], and is a " ACG Clinical Guidelines: Preferred and Maintenance Treatment in Adults with Ulcerative Colitis [11].
CMV is an opportunistic pathogenic virus whose infection can lead to a variety of symptomatic diseases
.
Patients with UC have a high susceptibility to CMV due to frequent hormonal or immunosuppressive therapy, malnutrition, and immune damage to the intestinal mucosal barrier [12].
Case 1: Patient was diagnosed with severe UC complicated with CMV infection
.
Therefore, choosing a virtalizumab that has both efficacy and safety is a more secure choice
.
After 4 courses of anti-infective treatment and 4 courses of vedolizumab treatment, CMV and colonoscopy results
were reviewed.
CMV turns negative
.
Colonoscopy showed good mucosal healing, and Mayo's endoscopic score was reduced from 3 to 1
.
This paper verifies that vedelizumab can bring clinical relief and mucosal healing to patients without affecting the systemic immune system
.
Historically, UC treatment has generally used the traditional "ladder" strategy, with escalation to biologic therapy
after repeated interventions that were poorly or intolerable by conventional medications.
This "pyramid" sequence of drug therapy may lead to irreversible intestinal damage due to the inability to achieve mucosal healing in patients with clear risk factors or progressive disease, resulting in adverse outcomes such as dysplasia and carcinogenesis [13].
The guidelines for the management of adult UC issued by AGA in 2020 have gradually weakened the concept of "ladder up", recommending that patients with moderate to severe UC with risk factors for disease progression should use biologics as early as possible to improve clinical outcomes, and do not recommend gradual escalation after 5-ASA failure [14].
Case 2 patient was a patient with chronic recurrent moderate UC, who had regularly used aminosalicylic acid and Chinese proprietary medicine but the efficacy was not good, and UC symptoms were recurrent and the lesions were extensive
.
Therefore, early escalation to biologics is a clinical decision
that leads to better prognosis.
After receiving 3 sessions of vederolizumab treatment, the Mayo score of the colonoscopy was reduced from 2 to 0, achieving clinical remission and complete mucosal healing
.
In summary, the efficacy, safety and maintenance of vedelizumab in the treatment of adult UC should not be underestimated
, whether for first-onset-naïve patients or recurrent chronic relapsing patients.
After the diagnosis of UC, the possibility of using biologics as soon as possible should be considered individually, so as to alleviate clinical symptoms, reduce patient pain, improve the quality of life of patients, and improve prognostic outcomes
.
Professor Wang Xiaoyan
Director of the Department of Gastroenterology, first-level chief physician, professor and doctoral supervisor of the Third Xiangya Hospital
Member of Ultrasound Endoscopy Group of Digestive Endoscopy Branch of Chinese Medical Association
Deputy leader of the Big Data Collaboration Group of the Digestive Endoscopy Branch of the Chinese Medical Association
Member of the Pancreatology Group of the Gastroenterology Branch of the Chinese Medical Association
Member of IBD Group of Gastroenterology Branch of Chinese Medical Association
Member of the Gastroenterologist Committee of the Chinese Medical Doctor Association
Member of the Standing Committee of the Digestive Endoscopy Committee of the Chinese Medical Doctor Association
Member of Pancreatic Cancer Group of Pancreatic Cancer Committee of Chinese Medical Doctor Association
Director of Digestive Endoscopy Training Base of Chinese Medical Doctor Association
Director of the Endoscopic Ultrasound Training Center of the Chinese Medical Doctor Association
President of Gastroenterologist Branch of Hunan Medical Association
Leader of the ultrasound endoscopy group of Hunan Medical Association
Director of Hunan Provincial Clinical Research Center for Minimally Invasive Diagnosis and Treatment of Digestive Endoscopy
Mainly engaged in endoscopic diagnosis and treatment of biliary and pancreatic diseases, basic and clinical research
on digestive system inflammation and tumors.He is good at minimally invasive diagnosis and treatment techniques such as EUS-guided minimally invasive diagnosis and treatment techniques, endoscopic submucosal dissection, full-thickness excision technology, endoscopic tunneling technology and ERCP
He has presided over 6 projects of the National Natural Science Foundation of China and published more than 60 SCI papers
He has won 4 Hunan Science and Technology Progress Awards and Teaching Awards, and 7 national patents
References:
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Am J Gastroenterol.
2019 ,114(3):384-413.
[2] Inflammatory Bowel Disease Group, Gastroenterology Branch of Chinese Medical Association.
Chinese Journal of Practical Internal Medicine.
2018,38(09):796-813.
[3] Macaluso FS, et al.
Dig Liver Dis.
2022,54(4):440-451.
[4] Juliao-Baños F, et al.
Rev Gastroenterol Mex (Engl Ed).
2022 ,87(3):342-361.
[5] Sandborn WJ,et al.
Gastroenterology.
2020 Feb; 158(3):562-572.
e12.
[6] Raine T,et al.
J Crohns Colitis.
2022,28; 16(1):2-17.
[7] Fumery M, et al.
Clin Gastroenterol Hepatol 2018, 16:343–56.
[8] Feagan BG,et al.
N Engl J Med.
2013,369(8):699-710.
[9] Colombel JF, et al.
Gut.
2017,66(5):839-851.
[10] Arijs I,et al.
Gut.
2018, 67(1):43-52.
[11] Rubin DT,et al.
Am J Gastroenterol.
2019,114(3):384-413.
[12] HUANG Ying, et al.
Journal of Clinical Gastroenterology,2020,32(01):25-30.
[13] Wang Xiaolei, et al.
Chinese Journal of Inflammatory Bowel Diseases.
2020;04(01):67-70.
[14] Joseph D Feuerstein,et al.
Gastroenterology.
2020,158(5):1450-1461.
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