Takeo Yoshihara1, Shinichiro Shinzaki1, Takahiro Amano1, Hideki Iijima1, Tetsuo Takehara1, Nagamu Inoue2, Motoi Uchino3, Motohiro Esaki4, Taku Kobayashi5, Masayuki Saruta6, Ken Sugimoto7, Shiro Nakamura8, Keisuke Hata9, Fumihito Hirai10, Sakiko Hiraoka11, Toshimitsu Fujii12, Minoru Matsuura13, Katsuyoshi Matsuoka14, Kenji Watanabe15, Hiroshi Nakase16, Mamoru Watanabe12,17. 1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan. 2. Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan. 3. Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan. 4. Division of Gastroenterology, Department of Internal Medicine, Saga University, Saga, Japan. 5. Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. 7. First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan. 8. Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan. 9. Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan. 10. Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 11. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 12. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan. 13. Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan. 14. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan. 15. Division of Internal Medicine, Center for Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan. 16. Department of Gastroenterology and Hepatology, School of Medicine, Sapporo Medical University, Hokkaido, Japan. 17. Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND AND AIM: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. METHODS: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6-12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios. RESULTS: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06-1.71], P = 0.015). The heterogeneity among studies was low (I2 = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. CONCLUSION: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.
BACKGROUND AND AIM: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. METHODS: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6-12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios. RESULTS: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06-1.71], P = 0.015). The heterogeneity among studies was low (I2 = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. CONCLUSION: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.