Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn’s Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study

Abstract

Background and Aims The optimal timing of treatment escalation in Crohn’s disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. Methods Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [<24 versus ≥24 months after diagnosis] and no anti-TNF treatment. Results A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001]. Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [p < 0.001 and p = 0.046, respectively] or were never [p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [p = 0.017], ambulatory [outpatient] hospital visits [p = 0.038], and a composite of any medical visits [p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF–treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016]. Conclusions In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome.

Long-term outcome of immunomodulator use in pediatric patients with inflammatory bowel disease

“…Although there is rising evidence that early treatment with anti-TNF agents is superior to early immunomodulators [19][20][21][22], the classic step-up approach still remains standard practice in most European centers. This is in part due to local restrictions that dictate when biologics can be initiated but also due to the lack of validated prognostic markers that can identify at diagnosis which patients will progress and require rescue therapy.…”

“…Common practice in most European pediatric centers is still a step-up approach where biological therapy is generally introduced after failure of corticosteroids, EEN and conventional immunomodulators. However, there is rising evidence that early treatment with anti-TNF is superior to early immunomodulators [16,[19][20][21][22]. Therefore, in the era where new classes of biologics are entering the market, the place of immunomodulators in the treatment of pediatric IBD is questioned.…”

Impact of early anti-TNF use on clinical outcomes in Crohn’s disease: a nationwide population-based study

“…Additionally, the Swiss IBD Cohort Study (SIBDCS) involving 540 CD patients (the data obtained from patients enrolled in SIBDCS between 2006 and 2012) found that treatment with anti-TNF agents within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared with initiating these drugs > 2 years after diagnosis (HR, 0.276; p = 0.018) [9]. Recently, the data obtained from SIBDCS involving more patients (246 early initiators and 696 late initiators) over a longer period of time (between 2006 and 2016) also showed that early anti-TNF administration within 2 years of CD diagnosis was associated with reduced risk of osteoporosis and anemia as well as bowel stenosis [10]. Furthermore, patients with early anti-TNF administration sought medical consultations significantly less frequently (including gastroenterologists in private practice, outpatient hospital visits, and a composite of any medical visits) and, by trend, showed lower rates of absence from work owing to CD, in contrast to patients with late anti-TNF administration [10].…”

“…Because previous studies have proposed a cut-off time of 2 years for early CD treatment [8][9][10][11], we conducted further analysis to assess the effect of initiation of anti-TNF therapy within 2 years after diagnosis. Of 1,207 patients, 873 started anti-TNF therapy within 2 years of diagnosis, and 334 started anti-TNF therapy > 2 years after diagnosis.…”

“…Indeed, previous studies have shown that use of immunomodulators (IMs) and/or biologics early in the course of the disease, known as top-down or accelerated step-up strategies, is superior to conventional step-up therapy in patients with CD [3,6,7]. In addition, several recent studies have compared early and late initiation of anti-TNF therapy in CD and have demonstrated better clinical outcomes in early initiators than in late initiators [8][9][10][11]. However, most previous studies on this topic have been conducted in Western countries.…”