Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Ooi, Choon Jin; Hilmi, Ida; Banerjee, Rupa; Chuah, Sai Wei; Ng, Siew C.; Shu, Wei; Makharia, Govind; Pisespongsa, Pises; Chen, Min Hu; Ran, Zhi Hua; Ye, Byong Duk; Park, Dong Il; Ling, Khoon Lin; Ong, David; Ahuja, Vineet; Goh, Khean Lee; Sollano, José D.; Lim, Wee Chian; Leung, Wai Keung; Ali, Raja Affendi Raja; Wu, Deng Chyang; Ong, Evan G.; Mustaffa, Nazri; Limsrivilai, Julajak; Hisamatsu, Tadakazu; Yang, Suk Kyun; Ouyang, Qi; Geary, Richard S.; Silva, Janaka H. De; Rerknimitr, Rungsun; Simadibrata, Marcellus; Abdullah, Murdani; Leong, Rupert W.; Colitis,

doi:10.1111/jgh.14648

Cited by 50 publications

(51 citation statements)

References 180 publications

(353 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 Lastly, since financial constraints affect drug usage in certain countries, one-fourth of the PCD patients stopped anti-TNF because of financial difficulties and only about one-third ceased therapy due to achievement of clinical remission. Utilisation of biological therapy is low in Asia due to its high cost and lack of insurance coverage [30,31] This leads to a higher chance of perianal CD relapse after discontinuation of biological agents. Larger prospective studies are required to assess the endpoints (ie deep fistula healing) required to be achieved before therapy can be definitively ceased and factors associated with future recurrence.…”

Section: Discussionmentioning

confidence: 99%

Stopping anti‐tumour necrosis factor therapy in patients with perianal Crohn’s disease

Mak¹,

Tang²,

Yip³

et al. 2019

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

Summary Background Little is known of the outcome of patients with perianal Crohn's disease after stopping anti‐tumour necrosis factor (TNF) therapy. Aim To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti‐TNF therapy. Methods Consecutive perianal CD patients treated with anti‐TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan‐Meier method. Results After a median follow‐up of 89 months (interquartile range [IQR]: 65‐173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti‐TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti‐TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01‐1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti‐TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58‐2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti‐TNF therapy after a median of 6 months. Conclusions More than half of the perianal CD patients developed relapse after stopping anti‐TNF therapy. Most regained response after resuming anti‐TNF. However, more than one‐fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti‐TNF is crucial in perianal CD.

show abstract

Section: Discussionmentioning

confidence: 99%

Stopping anti‐tumour necrosis factor therapy in patients with perianal Crohn’s disease

Mak¹,

Tang²,

Yip³

et al. 2019

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…The recent Asia Pacific guidelines have also not recommended routine TPMT testing in Asian patients. NUDT15 testing was suggested if available 34 . This is due to the fact that inspite of lower frequency of TMPT polyprophisms (3% vs 10% in Caucasians) and use of a much lower dose of thiopurines (median dose :1.3‐1.7) compared to weight‐based dosing (2‐3 mg/kg), the frequency of leucopenia is much higher (15%‐35% vs 5% in Caucasians) in studies from East Asia 11,15,16,35 .…”

Section: Discussionmentioning

confidence: 99%

NUDT15 C415T variant compared with TPMT genotyping in predicting azathioprine‐induced leucopenia: prospective analysis of 1014 inflammatory bowel disease patients in India

Banerjee

Vishnubhotla

Pal

et al. 2020

Aliment Pharmacol Ther

View full text Add to dashboard Cite

SummaryBackgroundRecent studies reported that Nudix Hydrolase 15(NUDT 15) gene variant (C415T) can better predict thiopurine induced leucopenia in Asian patients with inflammatory bowel disease (IBD) than thiopurine S‐methyl transferase (TPMT).AimTo evaluate the role of the NUDT variant compared with TPMT in predicting azathioprine induced leucopenia in Indian IBD patients.MethodsProspectively collected data of consecutive patients treated with azathioprine from a large IBD registry were analysed for side effects, discontinuation time, and initial and maximum dose tolerated. Genotyping of NUDT15 C415T (rs116855232; p.R139C) was carried out retrieving blood samples from bio‐repository employing real time polymerase chain reaction with age and sex‐matched healthy volunteers. The association of NUDT15 C415T with leucopenia (<3 × 109/L) and neutropenia (<1.5 × 109/L) was evaluated. TPMT genotyping was done in patients who developed leucopenia.ResultsAmong 1014 patients (mean age 35.84 ± 12.74 years; 61% males; 54% ulcerative colitis, 44% Crohn's disease and 2% IBD‐unclassified), 79 were excluded due to inadequate blood samples. Of the remaining 935, 81 (9%) developed leucopenia and 70 (7.5%) developed neutropenia. The variant “T” allele [heterozygous (CT) and homozygous (TT) versus wild type (CC)] was associated with a 19‐fold higher odds (OR19.35, 95% CI11.55‐32.42; P < 0.0001) of leucopenia and 21‐fold higher odds of neutropenia (OR21.41, 95% CI12.25‐37.41). There was significant difference in median dose tolerated between CC, CT and TT (1.35, 1.38 and 0.92 mg/kg body weight, respectively) (P = 0.037) and median duration of therapy (18, 15 and 10 months for CC/CT/TT) (P = 0.003). NUDT15 genotype was an independent risk factor for leucopenia (hazard ratio (HR): CT 11.31, 95% CI6.85‐18.03, P < 0.0001 and TT 31.283, 95% CI14.76‐66.30 compared to CC) and neutropenia (HR: CT 13.04, 95% CI7.65‐22.22, P < 0.0001 and TT 43.39, 95% CI20.21‐92.68 compared to CC). The sensitivities for predicting leucopenia and neutropenia by number of mutant NUDT 15 alleles based on additive predictive model were 66.67% and 70% with a receptor operator characteristic curve area under curve value of 0.791 and 0.807, respectively. Among patients with leucopenia, only 6.2% were heterozygous and none were homozygous for TPMT variants.ConclusionNUDT15 variant genotyping appears to be a better predictor for azathioprine‐induced leucopenia in an Indian population than TPMT with high accuracy and can be useful in optimizing azathioprine dosage.

show abstract

“…Crohn's disease (CD) is a chronic in ammatory bowel disease that is common among young people from their late teens to early 20s. In recent years, the number of patients with CD has increased not only in Europe and the United States, but also in Asia, including Japan [1,2]. In 2014, the estimated numbers of patients with CD in Japan is 70,700 [3].…”

Section: Read Full License Introductionmentioning

confidence: 99%

Influence of Preoperative Anti-TNF-Alpha Antibody Therapy on Postoperative Recurrence of Crohn’s Disease

Takeda¹,

Mizushima²,

Yoshihara³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Anti-TNFα antibody is effective for controlling inflammation caused by Crohn's disease. However, an increasing number of patients have recently undergone surgery after loss of response during maintenance therapy with anti-TNFα antibody. Aims: The purpose of this study was to examine how preoperative treatment using anti-TNFα antibody affects postoperative recurrence. Methods: Between January 2002 and June 2020, we retrospectively analyzed 90 patients with Crohn's disease who underwent bowel resection with anastomosis and received endoscopic evaluation within 18 months after surgery.Results: Fifty-seven patients had used anti-TNF antibodies preoperatively, and 33 had not. Of the 57 patients, 31 underwent surgery after loss of response. At the time of the first postoperative endoscopy, endoscopic recurrence occurred in 20 patients (35.1%) who used anti-TNFα antibody and 5 patients (15.2%) who did not use anti-TNFα antibody (p = 0.0419). The median symptomatic recurrence-free duration was 8 months in patients with loss of response and 44 months in patients without a loss of response (p = 0.0108). Conclusions: Patients who received anti-TNFα antibody preoperatively were prone to endoscopic recurrence. In addition, patients who experienced inefficacy before their surgeries were more likely to have recurrence, even after resuming post-operative anti-TNFα antibody treatment.

show abstract

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Cited by 50 publications

References 180 publications

Stopping anti‐tumour necrosis factor therapy in patients with perianal Crohn’s disease

Stopping anti‐tumour necrosis factor therapy in patients with perianal Crohn’s disease

NUDT15 C415T variant compared with TPMT genotyping in predicting azathioprine‐induced leucopenia: prospective analysis of 1014 inflammatory bowel disease patients in India

Influence of Preoperative Anti-TNF-Alpha Antibody Therapy on Postoperative Recurrence of Crohn’s Disease

Contact Info

Product

Resources

About