Infliximab or adalimumab in fistulizing Crohn’s disease (FCD)…that is a question?

Review by Dr. Edyta Tulewicz-Marti (Poland)

Study Summary 

Crohn’s disease may be challenging to manage, and fistulizing Crohn’s disease (FCD) can be even more difficult! The optimal treatment strategies include a multidisciplinary approach with both medical and surgical management. In this paper, the persistence of all dispensed biological agents was analysed using data from the Australian Pharmaceutical Benefits Scheme registry (2005-2021) for FCD. There were 5,739 lines of therapy in 4,466 patients over the 16-year period, with 17,144 patient-years of follow-up. Throughout therapy, 45.4% of patients used adalimumab, and 54.6% used infliximab. Additionally, 29.6% used thiopurine co-therapy at induction, while 4.2% used methotrexate.

As a result of this study, the first-line biologic (biologic-naive), infliximab, demonstrated superior overall and corticosteroid-free persistence compared to adalimumab (P = 0.0002 and P = 0.0021, respectively). When used after the first-line (biologic-exposed), there was no significant difference between agents for overall persistence (P = 0.064), although infliximab showed greater corticosteroid-free persistence (P = 0.030). Coinduction with thiopurines was associated with improved overall and corticosteroid-free persistence (P = 0.0002 and P = 0.045, respectively), although no difference was observed with methotrexate.

Commentary 

Fistulizing Crohn’s disease is one of the most difficult forms to manage and often requires surgical treatment. In terms of medical management, anti-TNF agents are often considered. Based on this real-world data in bio-naïve patients with FCD, infliximab was found to be superior to adalimumab in biologic-naïve patients, which has also been shown in other studies (1). Its efficacy has been demonstrated in previous research (2,3). In real-world evidence (RWE), data regarding both medications are comparable (4,5).

According to the data from this study, in biologic-exposed patients, there were no significant differences between infliximab and adalimumab. Thiopurine co-therapy was independently associated with improved agent persistence in FCD, an effect not observed with methotrexate. Therefore, when choosing the optimal medication for FCD, infliximab appears to be the best option. However, in patients who are experienced with biologic treatments, both agents can be good options. Additionally, immunosuppression should not be overlooked. How about other biological medications or small molecules? There are some data regarding Ustekinumab or Upadacitinib but.. it is another story…

Citation

1. Chetwood JD, Paramsothy S, Leong RW. Infliximab and Adalimumab in the Treatment of Fistulizing Crohn's Disease: A Propensity Score-Matched Analysis From the Prospective Persistence Australian National IBD Cohort (PANIC4) Study. Am J Gastroenterol. 2024 Dec 30;120(9):2093-2103
2. Sands, BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA,. et al. “Infliximab Maintenance Therapy for Fistulizing Crohn’s Disease”. The New England Journal of Medicine 350, no. 9 (2004): 876–85.
3. Present, DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK,. et al. “Infliximab for the Treatment of Fistulas in Patients With Crohn’s Disease”. The New England Journal of Medicine 340, no. 18 (1999): 1398–405
4.  Ji, CC, and Takano S.. “Clinical Efficacy of Adalimumab Versus Infliximab and the Factors Associated With Recurrence or Aggravation During Treatment of Anal Fistulas in Crohn’s Disease”. Intestinal Research 15, no. 2 (2017): 182–6
5. Malian, A, Rivière P, Bouchard D, Pigot F, Eléouet-Kaplan M, Favreau-Weltzer C, Poullenot F, and Laharie D.. “Pedictors of Perianal Fistula Relapse in Crohn’s Disease”. Inflammatory Bowel Disease 26, no. 6 (2020): 926–31

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