You can have both fish and bear paws!

Only for medical professionals to read for reference.
Two cases of hormone-dependent moderate UC patients were finally treated with vedelizumab to achieve clinical remission and laboratory indicators returned to normal
.

Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease that mainly affects the colorectal.
Its chronic recurrent clinical features not only bring physical pain to the patient, but also seriously affect the quality of life and work ability of the patient.
Has produced a huge social and economic burden
.

There is currently no effective cure for UC, but most patients can be effectively controlled through drug therapy [1]
.

Glucocorticoid is one of the traditional treatment drugs for UC, and it has been used in the treatment of UC for more than 50 years
.

However, some patients initially use hormones to be effective.
Once the hormone is reduced or the hormone is stopped, the patient's clinical symptoms will relapse.
This is called hormone-dependent UC (SD-UC)
.

In view of the unsatisfactory effect of traditional treatment on patients with SD-UC, which seriously affects the quality of life and health of patients, it is urgent to find new and more specific methods to treat [2]
.

Verdrizumab is a new type of intestinal-selective humanized monoclonal antibody that can be used to moderate to inadequate response, failure or intolerance to traditional treatments or tumor necrosis factor alpha (TNFα) inhibitors Severely active adults with Crohn's disease (CD) and UC patients [3]
.

In this issue, we invited Dr.
Xueli Ding from the Affiliated Hospital of Qingdao University to share two classic cases of SD-UC to see how well velizumab treatment performed
.

About the author Ding XueliDepartment of Gastroenterology, Affiliated Hospital of Qingdao University, Vice Chairman, Qingdao Medical Association Parenteral and Enteral Nutrition Branch, Member of Qingdao Medical Association Gastroenterology Branch Team Leader Shandong Provincial Medical Association Gastroenterology Branch Deputy Leader of Hepatobiliary Diseases Group of the Seventh Committee of Shandong Provincial Medical Association Digestive Endoscopy Society Colorectal Group Member and Secretary Ai Zai Yanchang Inflammatory Bowel Disease Foundation (CCCF) Doctor is good at A classic case of inflammatory bowel disease and endoscopy, male, 57 years old, with main complaint: diarrhea, mucus, pus and blood in the stool for 2 years, aggravated by half a year
.

Past history: diabetes, pulmonary heart disease, severe pulmonary hypertension
.

History of present illness: In 2019, the patient developed diarrhea, 2-3 times a day, unformed, and had a small amount of pus, blood and mucus.
The patient received symptomatic treatment
.

On September 10, 2020, the patient developed diarrhea, mucus, pus, and blood in the stool, 7-8 times a day, after more than 20 times, tenesmus, and repeated oral ulcers
.

Laboratory examination results showed that stool occult blood test (OB) (+), stool culture (-), albumin was 25g/L, hemoglobin (Hb) was 115g/L, C-reactive protein (CRP) was 107mg/L, cancer Embryonic antigen (CEA) is 7.
52ng/mL, B-type natriuretic peptide (BNP) is 4355ng/mL
.

Colonoscopy showed that the entire colonic mucosa was congested, edema, and ulcers were formed, which was considered UC
.

Sufficient hormone combined with mesalazine treatment was relieved
.

Figure 1.
Colonoscopy results.
In March 2021, symptoms recurred when prednisone was reduced to 2.
5 mg, mucus pus and blood in the stool 3-6 times a day, accompanied by abdominal pain, and the condition recurred
.

Laboratory examination results showed that stool OB (+), stool culture (-), albumin was 39g/L, CRP was 6.
9mg/L, EBV DNA was 2.
0×102copy/mL, EBV-IgA and IgG were positive, and IgM was normal , Hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) are positive
.

Intestinal ultrasound showed that the colon wall was diffusely thickened and surrounded by omentum tissue, and the blood flow signal increased.
Considering the UC (active phase), the range of involvement was from the lower part of the descending colon to the sigmoid colon, and lymph nodes were enlarged
.

Figure 2.
Results of bowel ultrasound.
Colonoscopy showed that the left colon mucosa was congested and edema, which was considered UC
.

Figure 3.
Colonoscopy results Clinical diagnosis: UC (chronic recurrence type extensive colonic active stage, moderate) Type 2 diabetic pulmonary heart disease Severe pulmonary hypertension Treatment process: The patient started to receive methylprednisolone + velizumab treatment, A Prednisolone (40mg qd) was slowly reduced, and velizumab was maintained at every 8 weeks after induction therapy at 0, 2 and 6 weeks (intravenous injection of 300 mg)
.

In July 2021, the colonoscopy was rechecked after 14 weeks of treatment with vedelizumab.
The results showed that the transverse colon mucosa showed scar-like changes, with scattered hyperplastic polypoid changes, and the mucosa below the cecum, ascending colon, and descending colon were normal
.

Figure 4.
Colonoscopy results.
Hormone reduction stopped at this time.
The patient had no abdominal pain, diarrhea, mucus, pus and blood in the stool.
Blood routine, CRP, erythrocyte sedimentation rate (ESR), liver and kidney function were all normal, and blood glucose was 7.
97mmol/L, achieving no hormones.
Clinical relief and mucosal healing
.

Classic case two patient, female, 41 years old, was admitted to the hospital on June 10, 2020 due to "abdominal pain with diarrhea for more than 5 years"
.

Past history: 19 years of history of tuberculosis and cured
.

History of present illness: In 2016, the patient developed diarrhea, pus, blood, mucus, and abdominal pain.
Colonoscopy revealed UC (E3 Mayo 3 points)
.

After a sufficient amount of mesalazine combined therapy was given, clinical remission and mucosal healing were achieved
.
After 1 year, the drug was stopped and the condition repeated .

From 2019 to 2020, the patient's condition repeated, mesalazine treatment gradually became ineffective, hormone enema has improved, but clinical remission and mucosal healing have not yet been achieved
.

Laboratory examination results showed that Hb was 103g/L, platelets were 372×109/L, albumin was 40.
26g/L, CRP and ESR were normal, stool culture (-), stool OB (+), specific for Mycobacterium tuberculosis The test result of sex cell immune response was positive
.

Chest CT showed old tuberculosis in the upper lobe of the right lung
.

CT of the abdomen showed that the walls of the transverse colon, descending colon, sigmoid colon, and rectum were slightly thicker, and part of the colon pocket structure disappeared
.

Colonoscopy showed that the mucosa of the transverse colon and descending colon were swollen, and scattered shallow ulcers were seen.
In the rectum, scattered shallow ulcers were seen in the mucosa near the anus
.

Figure 5.
Colonoscopy results.
Patients received preventive anti-tuberculosis + oral hormones + azathioprine (AZA) treatment.
Re-examination of colonoscopy revealed that the lesions were worse than before and there was hormone dependence
.

In 2020, laboratory examination results showed that hemoglobin was 98g/L, platelets were 369×109/L, albumin was 30.
26g/L, CRP was 9.
19mg/L, stool culture (-), stool OB (+)
.

The test result of specific cellular immune response of Mycobacterium tuberculosis was still positive, and the test result of mycobacterium γ-interferon release was 8.
21IU/ml
.

Chest CT showed old tuberculosis in the upper lobe of the right lung.
CT of the abdomen and pelvis revealed a slightly thicker colorectal wall with multiple small lymph nodes around it
.

Colonoscopy showed congestion and swelling of the cecum, ascending colon, transverse colon, descending sigmoid colon and rectal mucosa, the formation of superficial erosion ulcers, purulent secretions on the surface, disappearance of vascular network, spontaneous bleeding in some mucosa, fold-like structures in the ascending colon, and others The area changes like a lead pipe
.

Figure 6.
Colonoscopy results May 7 and May 21, 2020, received two infliximab treatment (300mg), plus thalidomide (75mg) orally
.

On May 28, 2020, it was changed to thalidomide tablets (100mg qn), combined with isoniazid and rifampicin 0.
3g/day
.

On June 10, 2020, the infliximab (300mg) treatment was performed again, the symptoms were not obvious, and the therapeutic drug monitoring (TDM) indicated that the concentration of infliximab was insufficient and the TNFα was high.
The patient was given intensive injection every 4 weeks, and the patient's symptoms gradually Some relief, stool 3-4 times a day, gradually disappeared pus and blood, abdominal pain relieved, no fever, regular injection of infliximab every 4 weeks
.

Clinical diagnosis: UC (chronic recurrence, full colon, active, moderate) old tuberculosis treatment process: because the patient failed to achieve mucosal healing and endoscopic remission after receiving infliximab treatment, infliximab was discontinued , Began to use vedelizumab treatment, induced remission at 0, 2 and 6 weeks, intensive treatment at the 10th week, and evaluated the efficacy before the 14th week
.

The patient's symptoms improved compared to before, stool 2-3 times a day, no blood, no abdominal pain, no fever, CRP and ESR returned to normal, anemia corrected, the results of the colonoscopy review are shown in the figure below
.

Figure 7.
Case summary of colonoscopy results According to the 2019 U.
S.
guidelines, hormones, anti-TNFα drugs, vedelizumab and tofacitinib are selected in parallel for the treatment of moderate to severe UC.
When the anti-TNFα drug response is not good, conversion can be considered Verdrizumab or tofacitinib [4]
.

We follow the guidelines, according to the comprehensive situation of the patients, transform in time while taking into account the safety, evaluate the efficacy, and achieve the treatment goals
.

The first patient was a hormone-dependent moderate to severe UC patient with multiple diseases.
After switching to vedelizumab, mucosal healing was achieved
.

In the second patient, clinical remission and mucosal healing were not achieved on the basis of traditional step-up therapy, and combined with old tuberculosis.
From the perspectives of safety, efficacy, and treatment goals, the mucosa was converted to velizumab treatment.
For healing, the regimen adopted is an intensive treatment regimen (additional induction of remission in the first 10 weeks)
.

Expert Profile Professor Ran Zhihua Chief Physician, Professor, and Doctoral Supervisor of Renji Hospital, Shanghai Jiaotong University School of Medicine.
Currently Director of Shanghai Inflammatory Bowel Disease Research Center, International Organization for Inflammatory Bowel Disease (IOIBD) Committee Member BRICS IBD Consortium Intestinal Disease Alliance) Founder and First Chairman European Crohn’s Disease and Colitis Organization (ECCO) Scientific Committee Judge, International Health Outcome Evaluation (ICHOM) Inflammatory Bowel Disease Steering Committee Member, Chinese Medical Equipment Association Digestive Disease Branch Standing Committee Member and Inflammation The head of the Gastroenterology Group serves as the deputy editor of Inflammatory Intestinal Disease, Journal of Gastroenterology and Hepatology Open, and the deputy editor of Chinese Journal of Inflammation.
Respond, but the dose cannot be reduced to less than the equivalent of 10 mg/day of prednisone within 3 months, or the patient relapses within 3 months after stopping the hormone
.

Previous studies have shown that glucocorticoids have short-term and long-term adverse effects; and patients receiving hormone therapy are associated with a higher risk of recurrence and colectomy [5]
.

UC itself is a chronic progressive disease.
As the course of the disease is prolonged, patients will have progressive features such as increased disease activity, disease expansion, colectomy, and canceration [6]
.

Therefore, for hormone-dependent patients, it is necessary to take more active and effective treatment measures as soon as possible, such as biological treatment
.

The Affiliated Hospital of Qingdao University shared 2 excellent cases.
The first case was a middle-aged male UC patient, who was hormone dependent, complicated with type 2 diabetes, pulmonary heart disease, severe pulmonary hypertension and many other complications
.

The second case is a middle-aged female, not only has hormone dependence, but also has a primary failure to respond to TNFa blockers, and also has old tuberculosis in the upper lobe of the right lung
.

With vedelizumab treatment, both patients achieved hormone-free clinical remission and mucosal healing
.

Verdrizumab is a new type of integrin antagonist with a new mechanism of action.
It can specifically antagonize α4β7 integrin and block activated α4β7 integrin and its ligand mucosal address cell adhesion molecule 1 (MAdCAM).
-1) to prevent the migration of T lymphocytes from the blood to the intestinal mucosa and reduce the local inflammation in the intestine [7]
.

The 2020 American Gastroenterology Association (AGA) guidelines recommend veldrizumab as the first-line biologic for the treatment of moderate to severe active UC (strong recommendation, moderate quality of evidence) [8]
.

In terms of efficacy, the GEMINI 1 study showed that veldrizumab achieved substantial improvement in the key symptoms of UC (rectal bleeding and diarrhea) within the second week of treatment, which was significantly different from placebo and had not been received in the past.
The efficacy of anti-TNFα drugs is better in patients; in the maintenance treatment phase, the mucosal healing rate and hormone-free remission rate of patients in the velizumab group are also significantly higher than those in the placebo group[9,10]
.

In addition, the first head-to-head VARSITY study in the field of inflammatory bowel disease that compares the efficacy of different biologics showed that the mucosal healing rate of patients treated with vedelizumab was significantly better than that of adalimumab at week 52, which has not been used before The curative effect is better in patients with anti-TNFα drugs [11]
.

From the above studies, it can be seen that in UC patients, vedelizumab is more effective as a first-line treatment
.

In the clinic, some patients are worried about whether the first-line use of vedelizumab may affect the efficacy of subsequent anti-TNFα therapy
.

In fact, the real-world EVOLVE study shows that the second-line anti-TNFα treatment after the failure of veldrizumab in the treatment of UC has similar efficacy compared with the first-line anti-TNFα treatment [11]
.

In terms of safety, vedelizumab performed well.
In long-term treatment, compared with placebo, veldrizumab has a lower incidence of infections and serious infections, and has nothing to do with the increase in the incidence of malignant tumors.
Summary According to the evidence, veldrizumab is considered to be the drug at the top of the safety pyramid [7,13]
.

Therefore, veldrizumab takes into account both efficacy and safety, and is the preferred therapeutic drug for UC patients
.

References: [1] Tian Lingling, Liu Lina.
Modern views on the treatment of ulcerative colitis[J].
World Chinese Journal of Digestion.
2016;24(7):1054-1063.
[2]Li Xia, Qu Bo, Jiang Haiyan, Et al.
Journal of Gastroenterology and Liver Disease.
2013;22(1):95-98.
[3] Hinojosa del Val J, Barreiro-de Acosta M.
Gastroenterología y Hepatología.
2019;42(10):650-656.
[4]Rubin DT,Ananthakrishnan AN,Siegel CA,et al.
Am J Gastroenterol.
2019 Mar;114(3):384-413.
[5]Burri E,Maillard MH,et al.
Digestion.
2020;101(suppl 1): 2-15.
[6] Torres J, Billioud V, Sachar DB, et al.
Inflamm Bowel Dis.
2012 Jul; 18(7): 1356-63.
[7] Zhou Qingyang, Qian Jiaming.
Chinese Journal of Digestion ,2020,40(02):141-144.
[8]Feuerstein JD,Isaacs KL,Schneider Y,et al.
Gastroenterology.
2020 Apr;158(5):1450-1461.
[9]FeaganBG,RutgeertsP,SandsBE, et al.
N Engl J Med,2013,369(8):699-710.
[10]Feagan BG,Lasch K,Lasch T,et al.
Clin Gastroenterol Hepatol.
2019;17(1):130-138.
[11]SandsBE ,Peyrin-BirouletL,LoftusEV,et al.
N Engl J Med,2019,381(13):1215-1226.
[12]Bressler B,et al.
UEG Week 2019.
P1091.
[13]Click B,Regueiro M.