Scientific Journal Of King Faisal University
Basic and Applied Sciences

ع

Scientific Journal of King Faisal University / Basic and Applied Sciences

Adalimumab Versus Ustekinumab in Egyptian Patients with Moderate to Severe Inflammatory Bowel Disease: A Cohort Study

(Amira Mohamed Elsawy Soliman, Abdel-Hameed Ibrahim Mohamed Ebid, Kamal El-Deen Abdelrahman Mohamed Al-Atrebi, Hagar Ahmed Ahmed Elessawy, Eman Magdy Elsayed Elyamany and Sara Mohamed Mohamed -Abdel- Motaleb)

Abstract

Inflammatory bowel disease (IBD) is a progressive, relapsing disorder. Biologics for patients with moderate-to-severe IBD have shown promising therapeutic outcomes. This research aims to compare the efficacy, safety and cost of adalimumab versus ustekinumab in a group of patients with IBD who failed treatment with infliximab. A prospective cohort study was performed on 108 patients, 53 of whom received adalimumab (Gp A) and 55 received ustekinumab (Gp U), followed up for 24 weeks. Clinical response, clinical remission and C-reactive protein (CRP) normalisation were assessed for efficacy; a cost-effectiveness analysis was conducted, and safety was evaluated. The clinical response was achieved by 86.8% of the patients in the Gp A and 92.7% of those in the Gp U group, respectively, without a significant statistical difference. The patients in the Gp A group experienced clinical remission and CRP normalisation in proportions of 47.1% and 37.3%, respectively. In contrast, the patients in the Gp U group experienced 69.8% and 58.5%, respectively, with significant statistical differences between the two groups. Adverse events were fewer in the Gp U than in the Gp A group, with a significant statistical difference. Ustekinumab was more costly than adalimumab, with a significant statistical difference between both groups. In conclusion, ustekinumab is considered more effective and safer than adalimumab in infliximab-experienced patients but with a higher cost in patients with moderate to severe IBD. 
PDF

References

Afify, A.F., Gado, M.A., Gohar, M.K. and Wadea, F.M. (2022). Clinical and biochemical response of treatment with anti-TNFα in Egyptian IBD patients: Zagazig University IBD Clinic experience. Zagazig University Medical Journal, 28(2), 342–54. DOI: 10.21608/zumj.2021.110464.2427
Ahmed, Z., Venkata, K., Zhang, N. and Malik, T.A. (2019). Comparative effectiveness of ustekinumab versus adalimumab in induction of clinical response and remission in Crohn’s disease: experience of a real-world cohort at a tertiary care inflammatory bowel disease referral center. Gastroenterology Research, 12(5), 245. DOI: 10.14740/gr1194
Alatab, S., Sepanlou, S.G., Ikuta, K., Vahedi, H., Bisignano, C., Safiri, S. and Naghavi, M. (2020). The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet Gastroenterology and Hepatology, 5(1), 17–30. DOI:10.1016/S2468-1253(19)30333-4
Aliyev, E.R., Hay, J.W. and Hwang, C. (2019). Cost‐effectiveness comparison of ustekinumab, infliximab, or adalimumab for the treatment of moderate‐severe crohn's disease in biologic‐naïve patients. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 39(2), 118–28. DOI:10.1002/phar.2208
Allegretti, J.R., Barnes, E.L., Stevens, B., Storm, M., Ananthakrishnan, A., Yajnik, V. and Korzenik, J. (2017). Predictors of clinical response and remission at 1 year among a multicenter cohort of patients with inflammatory bowel disease treated with vedolizumab. Digestive Diseases and Sciences, 62(6), 1590–6. DOI:10.1007/s10620-017-4549-3
Cai, Z., Wang, S. and Li, J. (2021). Treatment of inflammatory bowel disease: A comprehensive review. Front Med (Lausanne), 8(n/a), 765474. DOI:10.3389/fmed.2021.765474
Castiglione, F., Imperatore, N., Testa, A., de Sire, R., Nardone, O.M., Ricciolino, S. and Rispo, A. (2022). Exploring the concept of deep remission in Crohn’s disease: Correlation between transmural healing and biomarkers. Therapeutic Advances in Gastroenterology, 15(n/a), 1 – 13. DOI:10.1177/17562848221110643
Cerpa-Arencibia, A., Suarez-Ferrer, C., Poza-Cordón, J., Martín-Arranz, E., Ramírez, L. and Martín-Arranz, M.D. (2020). P679 What is the best strategy after failure to anti-TNF? Ustekinumab or other anti-TNF? Journal of Crohn's and Colitis, 14(1), S554. DOI:10.1093/ecco-jcc/jjz203.807
Cohen, D.J. and Reynolds, M.R. (2008). Interpreting the results of cost-effectiveness studies. Journal of the American College of Cardiology, 52(25), 2119–26. DOI:10.1016/j.jacc.2008.09.018
Dalal, R., Esckilsen, S., Barnes, E., McClure, E., Goodrick, H. and Allegretti, J. (2021). Predictors of corticosteroid-free remission after initiation of ustekinumab for ulcerative colitis: a real-world, multicenter cohort study in the United States. Journal of Crohn's and Colitis, 15(1), S348–9, DOI.org/10.1093/ecco-jcc/jjab076.448
Dos-Santos Silva, E.K., Cruz, J.A.W., da-Cunha, M.A.V.C., de-Moraes, T.P., Marques, S. and da-Silva, E.D. (2021). Cost-effectiveness in health: consolidated research and contemporary challenges. Humanities and Social Sciences Communications, 8(1), 1–10. DOI:10.1057/s41599-021-00940-5
Flynn, S. and Eisenstein, S. (2019). Inflammatory bowel disease presentation and diagnosis. Surgical Clinics, 99(6), 1051–62. DOI:10.1016/j.suc.2019.08.001
Forss, A., Clements, M., Myrelid, P., Strid, H., Söderman, C., Wagner, A. and Halfvarson, J. (2021). Prospective observational study on Stelara (ustekinumab) assessing effectiveness in Crohn’s disease (PROSE): A 16-week follow-up. Scandinavian Journal of Gastroenterology, 56(6), 680–6. DOI:10.1080/00365521.2021.1906946
Gisbert, J.P. and Chaparro, M. (2021). Primary failure to an anti-TNF agent in inflammatory bowel disease: switch (to a second anti-TNF agent) or swap (for another mechanism of action)? Journal of Clinical Medicine, 10(22), 5318. DOI:10.3390/jcm10225318
Hassan, E.A., Ramadan, H.K., Ismael, A.A., Mohamed, K.F., El-Attar, M.M. and Alhelali, I. (2017). Noninvasive biomarkers as surrogate predictors of clinical and endoscopic remission after infliximab induction in patients with refractory ulcerative colitis. Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association, 23(4), 238. DOI:10.4103/sjg.SJG_599_16
Hoekman, D.R., Diederen, K., Koot, B.G., Tabbers, M.M., Kindermann, A. and Benninga, M.A. (2016). Relationship of clinical symptoms with biomarkers of inflammation in pediatric inflammatory bowel disease. European Journal of Pediatrics, 175(10), 1335–42. DOI:10.1007/s00431-016-2762-2
Holmer, A. and Singh, S. (2019). Overall and comparative safety of biologic and immunosuppressive therapy in inflammatory bowel diseases. Expert Review of Clinical Immunology, 15(9), 969–79. DOI:10.1080/1744666X.2019.1646127
Ibing, S., Cho, J.H., Böttinger, E.P. and Ungaro, R.C. (2023). Second–Line biologic therapy following tumor necrosis factor antagonist failure: A Real–World propensity Score–Weighted analysis. Clinical Gastroenterology and Hepatology. 21(10), 2629–38. DOI: 10.1016/j.cgh.2023.01.038
Karthikeyan, A., Young, K.N., Moniruzzaman, M., Beyene, A.M., Do, K., Kalaiselvi, S. and Min, T. (2021). Curcumin and its modified formulations on inflammatory bowel disease (IBD): The story so far and future outlook. Pharmaceutics, 13(4), 484. DOI:10.3390/pharmaceutics13040484
Kim, F.S., Patel, P.V., Stekol, E., Ali, S., Hamandi, H., Heyman, M.B. and Verstraete, S.G. (2021). Experience using ustekinumab in pediatric patients with medically refractory Crohn disease. Journal of Pediatric Gastroenterology and Nutrition, 73(5), 610–4. DOI:10.1097/MPG.0000000000003230
Liefferinckx, C., Verstockt, B., Gils, A., Noman, M., Van-Kemseke, C., Macken, E., De Vos, M., Van-Moerkercke, W., Rahier, J.F., Bossuyt, P. and Dutré, J. (2019). Long-term clinical effectiveness of ustekinumab in patients with crohn's disease who failed biologic therapies: A national cohort study. Journal of Crohn's and Colitis, 13(11), 1401–9. DOI:10.1093/ecco-jcc/jjz080
Lin, X., Qiu, Y., Feng, R., Chen, B., He, Y., Zeng, Z. and Mao, R. (2020). Normalization of C-reactive protein predicts better outcome in patients with Crohn's disease with mucosal healing and deep remission. Clinical and Translational Gastroenterology, 11(2), e00135. DOI:10.14309/ctg.0000000000000135
Mentella, M.C., Scaldaferri, F., Pizzoferrato, M., Gasbarrini, A. and Miggiano, G.A.D. (2019). The association of disease activity, BMI and phase angle with vitamin D deficiency in patients with IBD. Nutrients, 11(11), 2583. DOI:10.3390/nu11112583
Moreno, L.O., Fernández-Tomé, S. and Abalo, R. (2021). Biological treatments in inflammatory bowel disease: A complex mix of mechanisms and actions. Biologics, 1(2), 189–210. DOI:10.3390/biologics1020012
Mosli, M., Alawadhi, S., Hasan, F., Abou-Rached, A., Sanai, F. and Danese, S. (2021). Incidence, prevalence, and clinical epidemiology of inflammatory bowel disease in the Arab world: A systematic review and meta-analysis. Inflammatory Intestinal Diseases, 6(3), 123–31. DOI:10.1159/000518003
Mühl, L., Becker, E., Müller, T.M., Atreya, R., Atreya, I., Neurath, M.F. and Zundler, S. (2021). Clinical experiences and predictors of success of treatment with vedolizumab in IBD patients: A cohort study. BMC Gastroenterology, 21(1), 1–10. DOI:10.1186/s12876-021-01604-z
Murdoch, T.B., O’Donnell, S., Silverberg, M.S. and Panaccione, R. (2015). Biomarkers as potential treatment targets in inflammatory bowel disease: A systematic review. Canadian Journal of Gastroenterology and Hepatology, 29(4), 203–8. DOI:10.1155/2015/389548
Okuyucu, M., Avcioğlu, U., Şenel, T. and Ustaoğlu, M. (2022). Investigation of the effects of anti-TNF agents on hemoglobin levels in patients with inflammatory bowel disease. Medicine, 101(35), e30118. DOI:10.1097/MD.0000000000030118
Prieto-Pérez, R., Almoguera, B., Cabaleiro, T., Hakonarson, H. and Abad-Santos, F. (2016). Association between genetic polymorphisms and response to anti-TNFs in patients with inflammatory bowel disease. International Journal of Molecular Sciences, 17(2), 225. DOI:10.3390/ijms17020225
Roda, G., Chien, N.S., Kotze, P.G., Argollo, M., Panaccione, R., Spinelli, A., Kaser, A., Peyrin-Biroulet, L. and Danese, S. (2020). Crohn's disease. Nature Reviews: Disease Primers, 6(1), 1–19. DOI:10.1038/s41572-020-0156-2
Sands, B.E., Irving, P.M., Hoops, T., Izanec, J.L., Gao, L.L., Gasink, C. and Zdena, Z. (2022). Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: A multicentre, randomised, double-blind, parallel-group, phase 3b trial. The Lancet, 399(10342), 2200–11. DOI:10.1016/S0140-6736(22)00688-2
Sauer, C.G. and Kugathasan, S. (2009). Pediatric inflammatory bowel disease: highlighting pediatric differences in IBD. Gastroenterology Clinics, 38(4), 611–28. DOI:10.1016/j.gtc.2009.07.010
Seyedian, S.S., Nokhostin, F. and Malamir, M.D. (2019). A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. Journal of Medicine and Life, 12(2), 113. DOI:10.25122/jml-2018-0075
Shamkh, M.A.A., Sakr, M.A., Abd-Alaty, W.H., Kamel, S.Y., Eltabbakh, M.M., Sherief, A.F. and Askar, S. (2022). A decade of inflammatory bowel disease: A single center experience in Egypt. The Egyptian Journal of Internal Medicine, 34(1), 22. DOI:10.1186/s43162-022-00115-x
Singh, S., George, J., Boland, B.S., Vande-Casteele, N. and Sandborn, W.J. (2018). Primary non-response to tumor necrosis factor antagonists is associated with inferior response to second-line biologics in patients with inflammatory bowel diseases: A systematic review and meta-analysis. Journal of Crohn's and Colitis, 12(6), 635–43. DOI:10.1093/ecco-jcc/jjy004
Strand, V., Balsa, A., Al-Saleh, J., Barile-Fabris, L., Horiuchi, T., Takeuchi, T. and Marshall, L. (2017). Immunogenicity of biologics in chronic inflammatory diseases: A systematic review. BioDrugs, 31(4), 299–316. DOI:10.1007/s40259-017-0231-8
Vallejo-Yagüe, E., Keystone, E.C., Kandhasamy, S., Micheroli, R., Finckh, A. and Burden, A.M. (2021). Primary and secondary non-response: In need of operational definitions in observational studies. Annals of the Rheumatic Diseases, 80(8), 961–4. DOI:10.1136/annrheumdis-2021-220202
Vermeire, S., Gils, A., Accossato, P., Lula, S. and Marren, A. (2018). Immunogenicity of biologics in inflammatory bowel disease. Therapeutic Advances in Gastroenterology, 11(n/a), 1756283X17750355. DOI:10.1177/1756283X17750355
Zacharias, P., Damiao, A.O.M.C., Moraes, A.C., Teixeira, F.V., Ludvig, J.C., Nones, R.B. and Kotze, P.G. (2017). Adalimumab for ulcerative colitis: results of a Brazilian multicenter observational study. Arquivos de Gastroenterologia, 54(4), 321–7. DOI:10.1590/S0004-2803.201700000-51
Zittan, E., Kabakchiev, B., Kelly, O.B., Milgrom, R., Nguyen, G.C., Croitoru, K. and Silverberg, M.S. (2017). Development of the Harvey-Bradshaw Index-pro (HBI-PRO) score to assess endoscopic disease activity in Crohn’s disease. Journal of Crohn's and Colitis, 11(5), 543–8. DOI: 10.1093/ecco-jcc/jjw200