Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort

Abstract

Background and aims: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27-83). Methods: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed. Results: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7% IFX was stopped, with the patient being in remission. Seventy patients (12.8%) had to stop IFX due to side effects and 118 (21.6%) due to loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. Conclusions: In this large real-life cohort of patients with CD, long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery.Crohn's disease (CD) is a disabling chronic relapsing inflammatory disorder of the bowel. Long-term experience with standard therapies for inflammatory bowel disease (IBD) up to the late 1990s demonstrated diverse limitations of these therapies in the treatment of IBD. Several population-based studies reported on the inability of corticosteroids to maintain remission, although these drugs have good short-term efficacy.1-5 Immunomodulators (IMMs) including azathioprine (AZA), its metabolite 6-mercaptopurine (6-MP) and the folate antagonist methotrexate (MTX) have a well-documented longterm efficacy in maintaining remission. [6][7][8][9][10]

Understanding Infliximab in Crohn’s Disease: The Long-Term Outcomes

“…The medical records of 492 unselected patients (or 464 with outcome data, used here as the denominator to calculate rates) treated with infliximab at the Mayo Clinic (1998-2002) were systematically reviewed. The study showed an 86 % initial response rate (or 80 % calculated on an ITT basis), similar to the 82-89 % reported in most other publications such as the pediatric REACH trial [5], the Edmonton cohort [6], the large Leuven cohort [7], the Leeds cohort [8], and the Targan initial RCT [1] but higher than the short-term response rate achieved in the ACCENT trial (65 %) [2]. This figure (82-89 %) also includes those with partial response, variably defined in the different studies.…”

“…1b). A total of 43 % of those with outcome data in the current report of Seminerio et al required at least one surgery at some time during the follow-up period after starting infliximab as compared with 24 % in the Leuven cohort [7]. Most other reports did not report on surgery rate leaving open the question of whether infliximab alters the natural history of the disease.…”

“…1, benchmarked by some other long-term real-life reports, most notably the Leuven cohort, which reviewed the outcome of 614 patients [7] and the safety of 734 patients [9]. Direct comparison between the studies is challenging in view of the different follow-up periods and definitions of response as well as the variable inclusion of patients with episodic treatment and fistulizing disease.…”

Anti-TNF Treatment in Crohn's Disease: Toward Tailored Therapy?

“…Approximately 10 % of patients with " refractory " or newly diagnosed Crohn ' s disease seem not to respond to anti-TNF treatment ( 7,8 ). Th e mechanism of this lack of effi cacy is unclear.…”

“…A recent report on the outcome of prolonged infl iximab therapy in patients with Crohn ' s disease revealed that aft er a median follow-up time of 55 months, 63 % of patients had sustained benefi t and 22 % experienced loss of response despite increases in dose and shortening of dosing intervals. Th e annual dropout rates averaged 11 % on episodic and 7 % on scheduled maintenance therapy ( 8 ).…”