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

Zunirah Ahmed, Krishna Venkata, Nan Zhang, Talha A Malik, Zunirah Ahmed, Krishna Venkata, Nan Zhang, Talha A Malik

Abstract

Background: There is paucity of head-to-head studies comparing the effectiveness of ustekinumab (UST) and adalimumab (ADA) in Crohn's disease (CD). Here we provide a real-world comparison of these two agents.

Methods: We conducted an ambidirectional cohort study. Each patient included had moderate to severe active CD. Clinical response and remission were assessed between 4 and 16 weeks after induction.

Results: Of a total of 163 patients, 97 were induced with ADA and 66 were induced with UST. Logistic regression model analysis adjusted based on effect size showed that ADA when compared to UST induced clinical response (73.2% vs. 50% (odds ratio (OR): 2.40; 95% confidence interval (CI): 1.14 - 5.07; P = 0.02)) and remission (44.3% vs. 27.7% (OR: 2.35; 95% CI: 1.07 - 5.16; P = 0.034) in a statistically significantly higher proportion of patients. Among tumor necrosis factor (TNF)-naive patients, when comparing ADA vs. UST, ADA was superior in inducing clinical response (69/89 (77.5%) vs. 4/10 (40%) (OR: 4.26; 95% CI: 1.08 - 16.84; P = 0.04)), but not remission (41/89 (46%) vs. 3/9 (33%) (OR: 1.64; 95% CI: 0.39 - 6.97; P = 0.503)). Among TNF-experienced patients, ADA was numerically inferior in inducing clinical response (2/8 (25%) vs. 29/56 (52%) (OR: 0.38; 95% CI: 0.07 - 1.94; P = 0.24)) and remission (2/8 (25%) vs. 15/56 (27%) (OR: 1.22; 95% CI: 0.22 - 6.81; P = 0.82)), but neither of these differences were statistically significant.

Conclusions: In a real-world setting, the rate of clinical response and remission was higher among patients with CD who received ADA compared to UST. Of note, however, despite the small sample sizes of TNF-experienced patients who received ADA and TNF-naive patients who received UST, the higher effectiveness of ADA in inducing clinical response and indeed remission among patients with CD with active disease appears to primarily be driven by those who are TNF-naive. Among TNF-experienced patients, UST may be superior in inducing clinical response and equally effective in inducing clinical remission when compared to ADA. Based on this study, one may infer that among TNF-experienced patients with CD with active disease, one could consider switching to an agent such as UST instead of a second approved TNF blocker. However, larger studies comparing the two agents are required.

Keywords: Adalimumab; Clinical remission; Clinical response; Crohn’s disease; Efficacy; TNF-experienced; TNF-naive; Ustekinumab.

Conflict of interest statement

The authors have declared no competing interests.

Copyright 2019, Ahmed et al.

Figures

Figure 1
Figure 1
Flow chart showing the criteria for included patients.

References

    1. Ranasinghe IR, Hsu R. StatPearls. Treasure Island (FL): 2019. Crohn disease.
    1. Feuerstein JD, Cheifetz AS. Crohn disease: epidemiology, diagnosis, and management. Mayo Clin Proc. 2017;92(7):1088–1103. doi: 10.1016/j.mayocp.2017.04.010.
    1. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54. doi: 10.1053/j.gastro.2011.10.001. e42; quiz e30.
    1. Wilkins T, Jarvis K, Patel J. Diagnosis and management of Crohn's disease. Am Fam Physician. 2011;84(12):1365–1375.
    1. Ephgrave K. Extra-intestinal manifestations of Crohn's disease. Surg Clin North Am. 2007;87(3):673–680. doi: 10.1016/j.suc.2007.03.003.
    1. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390–407. doi: 10.1038/ncpgasthep0528.
    1. Danese S, Fiocchi C. Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol. 2006;12(30):4807–4812. doi: 10.3748/wjg.v12.i30.4807.
    1. Cheifetz AS. Management of active Crohn disease. JAMA. 2013;309(20):2150–2158. doi: 10.1001/jama.2013.4466.
    1. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S. et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383–1395. doi: 10.1056/NEJMoa0904492.
    1. Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE. et al. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med. 2012;367(16):1519–1528. doi: 10.1056/NEJMoa1203572.
    1. Qiu Y, Chen BL, Mao R, Zhang SH, He Y, Zeng ZR, Ben-Horin S. et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFalpha dose intensification in Crohn's disease. J Gastroenterol. 2017;52(5):535–554. doi: 10.1007/s00535-017-1324-3.
    1. Seo GS, Lee SH. [Emerging therapies: what are promising in the near future?]. The Korean Journal of Gastroenterology. Taehan Sohwagi Hakhoe Chi. 2018;71:81–88. doi: 10.4166/kjg.2018.71.2.81.
    1. Kotze PG, Ma C, Almutairdi A, Panaccione R. Clinical utility of ustekinumab in Crohn's disease. J Inflamm Res. 2018;11:35–47. doi: 10.2147/JIR.S157358.
    1. Gottlieb A, Narang K. Ustekinumab in the treatment of psoriatic arthritis: latest findings and clinical potential. Ther Adv Musculoskelet Dis. 2013;5(5):277–285. doi: 10.1177/1759720X13501021.
    1. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA. et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2016;375(20):1946–1960. doi: 10.1056/NEJMoa1602773.
    1. Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J. et al. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology. 2008;135(4):1130–1141. doi: 10.1053/j.gastro.2008.07.014.
    1. Battat R, Kopylov U, Bessissow T, Bitton A, Cohen A, Jain A, Martel M. et al. Association Between Ustekinumab Trough Concentrations and Clinical, Biomarker, and Endoscopic Outcomes in Patients With Crohn's Disease. Clin Gastroenterol Hepatol. 2017;15(9):1427–1434. doi: 10.1016/j.cgh.2017.03.032. e1422.
    1. Kopylov U, Afif W, Cohen A, Bitton A, Wild G, Bessissow T, Wyse J. et al. Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn's disease—the McGill experience. J Crohns Colitis. 2014;8(11):1516–1522. doi: 10.1016/j.crohns.2014.06.005.
    1. Ma C, Fedorak RN, Kaplan GG, Dieleman LA, Devlin SM, Stern N, Kroeker KI. et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn's disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther. 2017;45(9):1232–1243. doi: 10.1111/apt.14016.
    1. Greenup AJ, Rosenfeld G, Bressler B. Ustekinumab use in Crohn's disease: a Canadian tertiary care centre experience. Scand J Gastroenterol. 2017;52(12):1354–1359. doi: 10.1080/00365521.2017.1373847.
    1. Wils P, Bouhnik Y, Michetti P, Flourie B, Brixi H, Bourrier A, Allez M. et al. Subcutaneous ustekinumab provides clinical benefit for two-thirds of patients with Crohn's disease refractory to anti-tumor necrosis factor agents. Clin Gastroenterol Hepatol. 2016;14(2):242–250. doi: 10.1016/j.cgh.2015.09.018. e241-242.
    1. Ma C, Fedorak RN, Kaplan GG, Dieleman LA, Devlin SM, Stern N, Kroeker KI. et al. Long-term Maintenance of Clinical, Endoscopic, and Radiographic Response to Ustekinumab in Moderate-to-Severe Crohn's Disease: Real-world Experience from a Multicenter Cohort Study. Inflamm Bowel Dis. 2017;23(5):833–839. doi: 10.1097/MIB.0000000000001074.
    1. Gendelman O, Weitzman D, Rosenberg V, Shalev V, Chodick G, Amital H. Characterization of adherence and persistence profile in a real-life population of patients treated with adalimumab. Br J Clin Pharmacol. 2018;84(4):786–795. doi: 10.1111/bcp.13494.
    1. Knyazev OV, Kagramanova AV, Ruchkina IN, Fadeeva NA, Lishchinskaya AA, Boldyreva ON, Zhulina EY. et al. [Efficacy of adalimumab for Crohn's disease in real clinical practice] Ter Arkh. 2017;89(2):20–27. doi: 10.17116/terarkh201789220-27.
    1. Danese S, Bonovas S, Peyrin-Biroulet L. Positioning ustekinumab in Crohn's disease: from clinical evidence to clinical practice. J Crohns Colitis. 2017;11(10):1258–1266. doi: 10.1093/ecco-jcc/jjx079.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren