Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

Chen-Wang Chang; Shu-Chen Wei; Jen-Wei Chou; Tzu-Chi Hsu; Chiao-Hsiung Chuang; Ching-Pin Lin; Wen-Hung Hsu; Hsu-Heng Yen; Jen-Kou Lin; Yi-Jen Fang; Horng-Yuan Wang; Hung-Hsin Lin; Deng Cheng Wu; Yen Hsuan Ni; Cheng-Yi Wang; Jau-Min Wong

doi:10.5217/ir.2014.12.4.287

Articles

Page Path: HOME > Intest Res > Volume 12(4); 2014 > Article

Original Article Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study: Chen-Wang Chang¹, Shu-Chen Wei², Jen-Wei Chou³, Tzu-Chi Hsu⁴, Chiao-Hsiung Chuang⁵, Ching-Pin Lin⁶, Wen-Hung Hsu⁷, Hsu-Heng Yen⁸, Jen-Kou Lin⁹, Yi-Jen Fang¹⁰, Horng-Yuan Wang¹, Hung-Hsin Lin⁹, Deng Cheng Wu⁷, Yen Hsuan Ni¹¹, Cheng-Yi Wang², Jau-Min Wong²; Intestinal Research 2014;12(4):287-292.
DOI: https://doi.org/10.5217/ir.2014.12.4.287
Published online: October 27, 2014

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; Mackay Junior College of Medicine, Nursing and Management, Taipei; Mackay Medical College, New Taipei, Taiwan.

²Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

³Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

⁴Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.

⁵Department of Internal Medicine, Medical College and Hospital, National Cheng-Kung University, Tainan, Taiwan.

⁶Division of Gastroenterology, Chung Shan Medical University, Taichung, Taiwan.

⁷Department of Gastroenterology, Kaohsiung Medical University, Kaohsiung, Taiwan.

⁸Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan.

⁹Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei; Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

¹⁰Division of Gastroenterology, Department of Medicine, Show Chwan Memorial Hospital, Changhuan, Taiwan.

¹¹Department of Pediatrics, National Taiwan University, Taipei, Taiwan.

Correspondence to Jau-Min Wong, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No.7 Chung-Shan South Road, Taipei 101, Taiwan. Tel: +886-2-23123456 ext. 65768, Fax: +886-2-23947927, jmwong@ntu.edu.tw

• Received: September 26, 2014 • Revised: October 10, 2014 • Accepted: October 11, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next

5,217 Views
58 Download
20 Web of Science
20 Crossref

Full Article

Download PDF

Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
REFERENCES

Abstract

Background/Aims
Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria.
Methods
A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline.
Results
A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to 12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy.
Conclusions
Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.
Keywords: Crohn disease; Adalimumab; Efficacy; Safety

INTRODUCTION

The incidence and prevalence of IBD, which includes CD and UC, are lower in Asian countries than in Western countries. However, this has been recently changing.1 CD causes intestinal transmural inflammation, presenting with ulceration and can involve the entire gastrointestinal tract. Prolonged ulceration with inflammation and fibrosis without healing can lead to stricture or other complications.2,3 Therefore, mucosal healing is one of the important goals in treating CD. Treating the inflamed mucosa is associated with a decreased hospitalization risk and surgical resection. Current medications such as 5-aminosalicylic acid and other immunomodulators can relieve the symptoms, but usually do not achieve deep mucosal remission. On the other hand, tumor necrosis factor-alpha antibodies (Anti-TNF-α) have been found to be effective in treating both the symptoms and mucosal inflammations of CD.4

Adalimumab (ADA), one of the available anti-TNF-α antibodies, is an effective therapy for inducing and maintaining remission of moderate to severe CD.5 In one retrospective analysis of 149 patients treated with ADA at a mean duration of 20 months, the results showed 45% anti-TNF-naïve patients and 32% anti-TNF-exposed patients achieved clinical remission. Fistulas healed in 19% and an improvement was seen in the additional 19% of the patients. Adverse events were also seen in 38% of patients, infection being the most common (20%). Mortality in CD patient due to ADA is rare (<1%).6

In Taiwan, dating back to 2008 and till 2014, ADA is the only one available biologics that could be used for CD patients. The criteria of ADA usage is more stringent than most of the other countries, such as Japan and Korea. So far, there was no published data about using ADA in moderate to severe CD patients in Asia. This study aims to evaluate the efficacy and adverse effects of using ADA for CD patients in Taiwan.

METHODS

1. Patients

Collaborating with the Taiwan Society of Inflammatory Bowel Disease (TSIBD), we conducted a retrospective analysis of 9 medical centers in Taiwan from Sep 2009 to Mar 2014. Moderate to severe CD patients who were treated with ADA were included and analyzed. Diagnosis of CD was based on clinical, radiological, and histological features. The clinical response and remission was measured by the standardized CDAI and clinical characteristics were collected and analyzed.

2. Inclusion Criteria

According to the guidelines from the National Health Insurance of Taiwan, reimbursement for ADA therapy depends on the following criteria: First of all, the diagnosis of CD has to be validated and the patient must be registered as having a catastrophic illness. Secondly, patients have received conventional therapies including 5-aminosalicylic acid, immunomodulators or steroids without having satisfactory results. Thirdly, the following medical criteria must be fulfilled: (1) Moderate to severe degree of CD (CDAI >250) despite conventional treatments; (2) Persistent abdominal fistula or anal fistula with symptoms despite medical or surgical treatments with CDAI >100.

3. Definitions of the Efficacy and Safety

The response of ADA was recorded using the following definitions: (1) Steroid-free: taper and then discontinue of steroid use after introducing the ADA. (2) Mucosal healing: Crohn's disease endoscopic index of severity (CDEIS) <6, or no ulceration in the endoscopic finding. (3) CR-70: a decrease in CDAI of at least 70 points. CR-100: a decrease in CDAI of at least 100 points. CR-150: a decrease in CDAI of at least 150 points. Clinical remission was defined as CDAI <150 or healing of fistula. (4) Primary non-response 70 (PNR-70) was defined as not attaining a CDAI decrease of 70 points compared with baseline, primary non-response 100 (PNR-100) was defined as not attaining a CDAI decrease of 100 points compared with baseline, and primary non-response 150 (PNR-150) was defined as not attaining a CDAI decrease of 150 points compared with baseline at week 12 respectively. (5) Adverse events: an undesired harmful effect during ADA treatment.

Extracted and analyzed data included demographics, remission and response rates with ADA, and the safety and efficacy of ADA.

4. Statistical Analysis

Continuous data was expressed as mean±SD and categorical data as percentages. Student's t-test was used for continuous variables and chi-square test for categorical variables. A value of P <0.05 was considered statistically significant. Regressions with a generalized linear model were also performed to assess the relationship between the level of CDAI-decrease and other parameters. The β-value and 95% CI were used to examine the potential relationships of the CDAI-decreased level and other parameters. All statistical analyses were conducted using SAS software, version 9.2 (SAS institute Inc., Cary, North Carolina, USA).

RESULTS

A total of 103 patients were enrolled from 9 medical centers. As shown in Table 1, about two thirds of the patients were male (66.9%). Their ages ranged from 16 to 86 years-old, with a mean±SD of 37.9±15.7 years-old. The duration of treatment ranged from 1 to 253 weeks, with the mean±SD of 74.6±59.1 weeks. Sixty percent of the patients received a combo therapy with ADA combined with azathioprine or methotrexate. The survival rate was 99% after the ADA treatment. For the Montreal classification, most patients were between 17 and 40 years-old (A2) (71.8%) with bowel stricturing (B2) (38.8%) located in the ileocolonic area (L3) (44.7%) (Table 1).

As shown in Fig. 1, the clinical response and remission after ADA treatment, was a CDAI (mean±SD) of 342.2±113.5, 201.3±77.2, 175.3±80.9 and 170.4±89.0 at weeks 0, 4, 8 and 12, respectively. The rates of CR-70 were 68.7%, 74.5% and 88.4% at weeks 4, 8 and 12, respectively. The rates of CR-100 were 61.2%, 68.6% and 79.7% at weeks 4, 8 and 12, respectively. In addition, the rates of CR-150 were 35.8%, 35.3% and 56.5% at weeks 4, 8 and 12, respectively (Fig. 2). After 12 weeks of treatment, 56.5% patients achieved clinical remission with the definition of CDAI <150 (Table 2).

47.6% of the patients receiving ADA became steroid-free as far as treatment. Sixty eight patients underwent endoscopic evaluation for mucosal healing from 6 to 12 months after ADA treatment. Of these patients, 25% (17/68) patients had CDEIS <6 or no mucosal ulceration and 27.9% (19/68) patients had improved endoscopic findings but still had ulcers (partial healing). When we used the CR-70 at 12 weeks after treatment as a cut-off point for primary response, the PNR-70 was only 11.6%. However, if we used the CR-100 at 12 weeks after treatment, the PNR-100 increased to 20.3%. When we used the CR-150 at 12 weeks after treatment, the PNR-150 was as high as 43.5%. There were still 16.5% patients who underwent ADA treatment that needed surgical intervention, mostly due to the stenosis or perforation complications (Table 3).

About 60% of the patients received the ADA and an immunomodulator as combo therapy. By using generalized linear regression models, we found that there was a significant difference in the CDAI-decreased level at week 8 when comparing the combo and monotherapy (using ADA alone) with the CDAI decreasing for the combo group by 158.5±114.2 and 101.0±75.6 for the monotherapy group (P =0.02) (Table 4).

Adverse events were observed in 9.7% of the patients receiving ADA treatment. Six patients (6/103, 5.8%) had infections and one patient died of sepsis. Other associated adverse events such as intracranial hemorrhage (1/103), myofascial pain (1/103), palpitation (1/103) and a new onset right parotid pleomorphic adenoma (1/103) were also noted. No malignancies were found, so far, in these patients (Table 5). There was also no statistical difference between monotherapy and combo therapy (P =0.18, chi-square test) in adverse events.

DISCUSSION

The safety and efficacy of ADA for CD have been extensively tested in Western countries, but much less so in Asian countries.3,6,7,8,9,10,11 In Japan, ADA was approved for CD treatment since 2010. Anti-TNF-α agents, such as infliximab (IFX) or ADA, are suggested for refractory cases, remission maintenance, prevention of postoperative relapse and anal lesions. Refractory cases are defined as steroid-resistant, steroid-dependent and cases that surgical treatment is a consideration.12 In Taiwan, as of September 2014, ADA is the only available anti-TNF-α antibody for CD patients. According to the guidelines from the National Health Insurance of Taiwan, the criteria for using ADA in CD are more stringent and limited to the moderate to severe CD with CDAI more than 250 and not responded to conventional therapy. Historically, IBD has been rare in the Far East, however, the incidence and prevalence of IBD are increasing now.13 This phenomenon was also found to be true in Taiwan.14 In Asia, Japan and Korea, so far, have the highest incidence and prevalence for IBD and they approved the use of anti-TNF antibodies similar to its use in western countries. The governments of these countries also support the treatment when IBD patients register and are in need of the antibody treatment. However, most other Asian countries do not provide such governmental support for IBD patients or only providing limited support. Therefore, balancing the cost and benefit of such a treatment is an important issue. Therefore, we set out to examine whether there is an added benefit of antibody treatment using the very stringent criteria used in Taiwan, compared with those countries using the anti-TNF antibody treatment without such stringent criteria.

CDAI is a validated score for CD monitoring with a range from 0 to approximately 600. CDAI below 150 points is considered a reasonable non-active disease status. A CDAI score of 150-219 is defined as a mildly active disease and scores of 220-450 as moderately active disease. Finally, a severe degree is defined as a cut-off value of more than 450 points.15 In our study, the criteria of "moderate to severe degree" is even more stringent, which the CDAI was more than 250 points in order to get the reimbursement of ADA usage. In the Clinical Assessment of ADA Safety and Efficacy Studied as Induction Therapy in Crohn's Disease I (CLASS I) and the Crohn's Trial of the Fully Human Antibody ADA for Remission Maintenance (CHARM) studies, the CR-70 was 54-59% and 64.1% at week 4, respectively.16,17 Our result showed similar findings with 68.7% of the patients attaining CR-70 at week 4, and a better CR-70 at week 12 (88.4%) compared with the Extend the Safety and Efficacy of ADA Through Endoscopic Healing (EXTEND) trial (65-66%).4 As for the clinical remission rate, previous studies also had different results. In the EXTEND trial, the rates of remission were 52% and 28% at week 12 and week 52, respectively. In the CHARM study, the remission rates were 40% in the every other week ADA treatment group, and 47% in the group of weekly ADA treatment, respectively, at week 26.17 Our results showed that 56.5% patients had clinical remission at week 12. For comparing the combo or monotherapy, we found that ADA with concomitant azathioprine was significantly more effective for decreasing the CDAI level after treatment, which was consistent to the previous report.18 In considering the side effects, there's no statistically difference between the combo and monotherapy group (12.9%, 4.9%, respectively; P =0.18).

Becoming steroid-free is another aim in treating CD patients. According to our results, 47.6% patients achieved steroid-free disease management. A previous study showed similar findings with a 44.4% steroid-free rate during anti-TNF-α (IFX) treatment.19 Mucosal healing is the current goal of treating CD patients to reduce the need for hospitalizations and surgery.7 In our study, the mucosal healing rate was 25% after 6-12 months treatment, which is similar to the EXTEND trial of 27% at week 12.4 In a previous report, when using anti-TNF treatment (ADA 74, IFX 109) in CD patients with the median treatment duration as 23 months, 43% patient case had achieved deep mucosal healing.20 Our results showed that most of our patients did not achieve deep mucosal healing after 6-12 months treatment, it implies that longer treatment is needed to help improve the mucosal healing rate, especially when treating the moderate to severe CD patients.

Adverse events of ADA are another important issue for treating CD patients. From the EXTEND trial, adverse events and serious adverse events were noted in 42.2% and 6.3% of the patients.7 Serious infections developed during IFX treatment for CD was noted in 4.9% of the patients.19 Our study also showed that the adverse events rate is 9.7%, which were mostly infections (5.8%). In CHARM trial, there were 3 cases (0.2%) with active tuberculosis (TB) during treatment.21 Two cases of TB (1.9%) were also noted during treatment in our study. One was de novo TB and the other as latent TB, both received anti-TB treatment consequently.

There were limitations of our study. First, this is a retrospective study with missing data. Therefore, how was the proportion of patients with perianal lesions, how many patients were under steroid before they used the ADA were not able to be known from this study. Second, since there was no universal protocol of endoscopic evaluation for mucosal healing, we could only have the endoscopic results as a range of 6 to 12 months for evaluating the mucosa healing rate.

In summary, our results have demonstrated that even using more stringent criteria for choosing CD patients to treat with anti-TNF-α, the efficacy is comparable to those not under such stringent criteria. We also observed similar rates of adverse effects. However, more than one year of anti-TNF treatment might be needed to increase the deep mucosal healing rate for CD patients.

NOTES

Financial support: None.

Conflict of interest: None.

REFERENCES

1. Sung JJ, Kamm MA, Marteau P. Asian perspectives in the management of inflammatory bowel disease: findings from a recent survey. J Gastroenterol Hepatol 2010;25:183–193.PMID: 19929931.Article PubMed
2. Rieder F, Fiocchi C. Intestinal fibrosis in inflammatory bowel disease - current knowledge and future perspectives. J Crohns Colitis 2008;2:279–290.PMID: 21172225.Article PubMed PDF
3. Tursi A, Elisei W, Picchio M, et al. Effectiveness and safety of infliximab and adalimumab for ambulatory Crohn's disease patients in primary gastroenterology centres. Eur J Intern Med 2014;25:485–490.PMID: 24631020.Article PubMed
4. Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology 2012;142:1102–1111.PMID: 22326435.Article PubMed
5. Peters CP, Eshuis EJ, Toxopeus FM, et al. Adalimumab for Crohn's disease: long-term sustained benefit in a population-based cohort of 438 patients. J Crohns Colitis 2014;8:866–875.PMID: 24491515.Article PubMed PDF
6. Teriaky A, Gregor J, Yan B, Ponich T, Chande N, Mosli M. The safety and efficacy of adalimumab in patients with Crohn's disease: the experience of a single Canadian tertiary care centre. Scand J Gastroenterol 2014;49:280–286.PMID: 24329040.Article PubMed
7. Asgharpour A, Cheng J, Bickston SJ. Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial. Clin Exp Gastroenterol 2013;6:153–160.PMID: 24039442.PubMed PMC
8. Zorzi F, Zuzzi S, Onali S, et al. Efficacy and safety of infliximab and adalimumab in Crohn's disease: a single centre study. Aliment Pharmacol Ther 2012;35:1397–1407.PMID: 22519466.Article PubMed
9. Lichtenstein GR, Panaccione R, Mallarkey G. Efficacy and safety of adalimumab in Crohn's disease. Therap Adv Gastroenterol 2008;1:43–50.Article PubMed PMC
10. Seiderer J, Brand S, Dambacher J, et al. Adalimumab in patients with Crohn's disease--safety and efficacy in an open-label single centre study. Aliment Pharmacol Ther 2007;25:787–796.PMID: 17373917.Article PubMed
11. Hinojosa J, Gomollon F, Garcia S, et al. Efficacy and safety of short-term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open-label, multicentre trial. Aliment Pharmacol Ther 2007;25:409–418.PMID: 17269996.Article PubMed
12. Ueno F, Matsui T, Matsumoto T, Matsuoka K, Watanabe M, Hibi T. Evidence-based clinical practice guidelines for Crohn's disease, integrated with formal consensus of experts in Japan. J Gastroenterol 2013;48:31–72.PMID: 23090001.Article PubMed
13. Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 2008;103:3167–3182.PMID: 19086963.Article PubMed
14. Wei SC, Lin MH, Tung CC, et al. A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan. BMC Gastroenterol 2013;13:166PMID: 24314308.Article PubMed PMC PDF
15. Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Review article: Crohn's disease: monitoring disease activity. Aliment Pharmacol Ther 2003;17(Suppl 2): 11–17.PMID: 12786607.Article PubMed
16. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology 2006;130:323–333.PMID: 16472588.Article PubMed
17. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 2007;132:52–65.PMID: 17241859.Article PubMed
18. Ishida K, Inoue T, Fujiwara K, et al. Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn's disease patients. World J Gastroenterol 2013;19:2676–2682.PMID: 23674875.Article PubMed PMC
19. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010;362:1383–1395.PMID: 20393175.Article PubMed
20. Molander P, Sipponen T, Kemppainen H, et al. Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD. J Crohns Colitis 2013;7:730–735.PMID: 23182163.Article PubMed PDF
21. Panaccione R, Colombel JF, Sandborn WJ, et al. Adalimumab maintains remission of Crohn's disease after up to 4 years of treatment: data from CHARM and ADHERE. Aliment Pharmacol Ther 2013;38:1236–1247.PMID: 24134498.Article PubMed PMC

Fig. 1

Levels of CDAI at week 0, week 4, week 8 and week 12 of CD patients receiving adalimumab treatment.

Fig. 2

The percentages of CR-70, CR-100 and CR-150 at week 4, week 8 and week 12. CR-70, decrease in CDAI of at least 70 points; CR-100, decrease in CDAI of at least 100 points; CR-150, decrease in CDAI of at least 150 points.

Table 1

Demographics of the Study Patients

Values are presented as mean±SD or n (%).

^*Combination with azathioprine or methotrexate.

Table 2

The Decrease of CDAI Compared With Baseline at Week 4, 8 and 12

Valuses are presented as mean±SD or % (n).

^*There were 6 patients who received adalimumab due to persistent abdominal fistula and the baseline CDAI <150.

CR-70, decrease in CDAI of at least 70 points; CR-100, decrease in CDAI of at least 100 points; CR-150, decrease in CDAI of at least 150 points.

Table 3

Efficacy of Adalimumab (n=103)

^*The definition of clinical remission is CDAI <150 points.

^†PNR-70 (primary non-response): did not attain a CDAI decrease of 70 points compared with baseline.

CDEIS, Crohn's disease endoscopic index of severity.

Table 4

The Relationship Between CDAI-Decrease Levels (Week 4, 8 and 12) and Parameters^*

^*Data was analyzed with generalized linear regression models.

^†Combination of azathioprine/methotrexate and adalimumab.

Table 5

Adverse Events During Adalimumab Treatment (n=103)

^*Two bacterial infections, 2 tuberculosis and 2 herpes zoster infections. In addition, one patient died due to sepsis.

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

Saudi consensus guidance for the diagnosis and management of inflammatory bowel disease in children and adolescents
Omar I. Saadah, Turki AlAmeel, Ahmed Al Sarkhy, Mohammed Hasosah, Abdulrahman Al-Hussaini, Majid A. Almadi, Badr Al-Bawardy, Talal A. Altuwaijri, Mohammed AlEdreesi, Shakir A. Bakkari, Othman R. Alharbi, Nahla A. Azzam, Abdulelah Almutairdi, Khalidah A. A
Saudi Journal of Gastroenterology.2024;[Epub] CrossRef
Real‐world experience of adalimumab therapy for patients with ulcerative colitis: A single tertiary medical center experience in Central Taiwan
Hsu‐Heng Yen, Yu‐Chun Hsu, Chu‐Hsuan Kuo, Tsui‐Chun Hsu, Yang‐Yuan Chen
Advances in Digestive Medicine.2023; 10(1): 28. CrossRef
Seronegative spondyloarthropathy-associated inflammatory bowel disease
Chrong-Reen Wang, Hung-Wen Tsai
World Journal of Gastroenterology.2023; 29(3): 450. CrossRef
Is the frequency of dietitian support associated with greater clinical improvements in adults with Crohn's disease undertaking exclusive enteral nutrition?
Liz Purcell, Rumbidzai Mutsekwa, Rebecca Angus, Dheeraj Shukla, Michelle Palmer
Journal of Human Nutrition and Dietetics.2022; 35(3): 435. CrossRef
The Antinociceptive Effect of Adalimumab, a TNF-Alpha Inhibitor, in a Mice Model of Inflammatory Pain
Mehmet ÖZ, Hasan ŞİMŞEK
Türk Doğa ve Fen Dergisi.2022; 11(3): 89. CrossRef
Clinical features and treatment of inflammatory bowel disease in a low-incidence area
Hsu-Heng Yen, Tsui-Chun Hsu, Mei-Wen Chen, Pei-Yuan Su, Yang-Yuan Chen
Medicine.2021; 100(10): e25090. CrossRef
Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study
Hsu-Heng Yen, Meng-Tzu Weng, Chien-Chih Tung, Yu-Ting Wang, Yuan Ting Chang, Chin-Hao Chang, Ming-Jium Shieh, Jau-Min Wong, Shu-Chen Wei
Intestinal Research.2019; 17(1): 54. CrossRef
Administration Timing Is the Best Clinical Outcome Predictor for Adalimumab Administration in Crohn's Disease
Mauro Mastronardi, Margherita Curlo, Elisabetta Cavalcanti, Osvaldo Burattini, Renato Cuppone, Romina Tauro, Stefania De Santis, Grazia Serino, Pasqua Letizia Pesole, Elisa Stasi, Maria Lucia Caruso, Rossella Donghia, Vito Guerra, Pietro Giorgio, Marcello
Frontiers in Medicine.2019;[Epub] CrossRef
Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment
Dong Il Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin-Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasu
Intestinal Research.2018; 16(1): 4. CrossRef
Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti‐tumor necrosis factor treatment. Part 1: Risk assessment
Dong II Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin‐Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasu
Journal of Gastroenterology and Hepatology.2018; 33(1): 20. CrossRef
High risk of tuberculosis during infliximab therapy despite tuberculosis screening in inflammatory bowel disease patients in India
Ashish Agarwal, Saurabh Kedia, Saransh Jain, Vipin Gupta, Sawan Bopanna, Dawesh P Yadav, Sandeep Goyal, Venigalla Pratap Mouli, Rajan Dhingra, Govind Makharia, Vineet Ahuja
Intestinal Research.2018; 16(4): 588. CrossRef
Balloon-Assisted Enteroscopy and Capsule Endoscopy in Suspected Small Bowel Crohn’s Disease
Hsu-Heng Yen, Chen-Wang Chang, Jen-Wei Chou, Shu-Chen Wei
Clinical Endoscopy.2017; 50(5): 417. CrossRef
Long-Term Outcomes of Adalimumab Treatment in 254 Patients with Crohn’s Disease: A Hospital-Based Cohort Study from Korea
Hyungil Seo, Byong Duk Ye, Eun Mi Song, Sun-Ho Lee, Kiju Chang, Ho-Su Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Kyung-Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang
Digestive Diseases and Sciences.2017; 62(10): 2882. CrossRef
Rare occurrence of inflammatory bowel disease in a cohort of Han Chinese ankylosing spondylitis patients- a single institute study
Chrong-Reen Wang, Chia-Tse Weng, Chung-Ta Lee, Kuo-Yuan Huang, Sheng-Min Hsu, Ming-Fei Liu
Scientific Reports.2017;[Epub] CrossRef
Understanding the complications of anti‐tumor necrosis factor therapy in East Asian patients with inflammatory bowel disease
Jae Hee Cheon
Journal of Gastroenterology and Hepatology.2017; 32(4): 769. CrossRef
Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials
Zong Mei Zhang, Wei Li, Xue Liang Jiang
Gut and Liver.2016; 10(2): 262. CrossRef
Crohn's Disease: Specific Concerns in the Elderly
Wei-Chen Lin, Ming-Jen Chen, Cheng-Hsin Chu, Tsang-En Wang, Horng-Yuan Wang, Shou-Chuan Shih, Chen-Wang Chang
International Journal of Gerontology.2016; 10(3): 126. CrossRef
Efficacy of Adalimumab in Korean Patients with Crohn's Disease
Il Woong Sohn, Sung Tae Kim, Bun Kim, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Tae Il Kim, Won Ho Kim, Jae Hee Cheon
Gut and Liver.2016; 10(2): 255. CrossRef
Factors Contributing to the Preference of Korean Patients with Crohn's Disease When Selecting an Anti-Tumor Necrosis Factor Agent (CHOICE Study)
Eun Soo Kim, Kyeong Ok Kim, Byung Ik Jang, Chang Kyun Lee, Hyo Jong Kim, Kang-Moon Lee, You Sun Kim, Chang Soo Eun, Sung-Ae Jung, Suk-Kyun Yang, Jun Lee, Tae-Oh Kim, Yunho Jung, Geom Seog Seo, Soon Man Yoon
Gut and Liver.2016;[Epub] CrossRef
Laparoscopic bowel resection for pediatric inflammatory bowel disease
Justin B. Mahida, Lindsey Asti, Katherine J. Deans, Peter C. Minneci, Benedict C. Nwomeh
Journal of Surgical Research.2015; 199(1): 130. CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

Intest Res. 2014;12(4):287-292. Published online October 27, 2014

DOI: https://doi.org/10.5217/ir.2014.12.4.287

XML Download

Figure

Related articles

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

Fig. 1 Levels of CDAI at week 0, week 4, week 8 and week 12 of CD patients receiving adalimumab treatment.

Fig. 2 The percentages of CR-70, CR-100 and CR-150 at week 4, week 8 and week 12. CR-70, decrease in CDAI of at least 70 points; CR-100, decrease in CDAI of at least 100 points; CR-150, decrease in CDAI of at least 150 points.

Fig. 1

Fig. 2

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

Table 1

Demographics of the Study Patients

Values are presented as mean±SD or n (%).

^*Combination with azathioprine or methotrexate.

Table 2

The Decrease of CDAI Compared With Baseline at Week 4, 8 and 12

Valuses are presented as mean±SD or % (n).

^*There were 6 patients who received adalimumab due to persistent abdominal fistula and the baseline CDAI <150.

CR-70, decrease in CDAI of at least 70 points; CR-100, decrease in CDAI of at least 100 points; CR-150, decrease in CDAI of at least 150 points.

Table 3

Efficacy of Adalimumab (n=103)

^*The definition of clinical remission is CDAI <150 points.

^†PNR-70 (primary non-response): did not attain a CDAI decrease of 70 points compared with baseline.

CDEIS, Crohn's disease endoscopic index of severity.

Table 4

The Relationship Between CDAI-Decrease Levels (Week 4, 8 and 12) and Parameters^*

^*Data was analyzed with generalized linear regression models.

^†Combination of azathioprine/methotrexate and adalimumab.

Table 5

Adverse Events During Adalimumab Treatment (n=103)

^*Two bacterial infections, 2 tuberculosis and 2 herpes zoster infections. In addition, one patient died due to sepsis.

Table 1 Demographics of the Study Patients

Values are presented as mean±SD or n (%).

^*Combination with azathioprine or methotrexate.

Table 2 The Decrease of CDAI Compared With Baseline at Week 4, 8 and 12

Valuses are presented as mean±SD or % (n).

^*There were 6 patients who received adalimumab due to persistent abdominal fistula and the baseline CDAI <150.

CR-70, decrease in CDAI of at least 70 points; CR-100, decrease in CDAI of at least 100 points; CR-150, decrease in CDAI of at least 150 points.

Table 3 Efficacy of Adalimumab (n=103)

^*The definition of clinical remission is CDAI <150 points.

^†PNR-70 (primary non-response): did not attain a CDAI decrease of 70 points compared with baseline.

CDEIS, Crohn's disease endoscopic index of severity.

Table 4 The Relationship Between CDAI-Decrease Levels (Week 4, 8 and 12) and Parameters*

^*Data was analyzed with generalized linear regression models.

^†Combination of azathioprine/methotrexate and adalimumab.

Table 5 Adverse Events During Adalimumab Treatment (n=103)

^*Two bacterial infections, 2 tuberculosis and 2 herpes zoster infections. In addition, one patient died due to sepsis.