Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

Abstract

Background: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a potentially safer but under-studied alternative.Aim: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies.Methods: We studied the clinical success and infliximab consumption with both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation.Results: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no significant differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions:In this study, optimised infliximab monotherapy was as clinically effective as combination therapy, but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.

De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

“…In a retrospective study of 149 patients with IBD (94 patients with Crohn's disease and 55 with ulcerative colitis), the less favourable pharmacokinetic profile initially observed with infliximab monotherapy could be overcome with dose escalation based on close therapeutic drug monitoring, with no difference in infliximab discontinuation, mucosal healing, hospitalisation, or long-term steroid use over a median follow-up of 19 months. 41 Concordant results were reported in a second retrospective study, in which early infliximab dose escalation resulted in similar clinical outcomes and infliximab trough concentrations regardless of concurrent immuno-modulator. 42 Taken together, although these data highlight the potential negative effect of immunomodulator withdrawal on anti-TNF pharmacokinetics and immunogenicity, an increased risk of relapse has not been shown, and proactive therapeutic drug monitoring emerges as a strategy to maintain anti-TNF efficacy.…”

“…The authors also did a meta-analysis, which supported their findings. 46 The relapse rate at 1 year was 39% (95% CI [35][36][37][38][39][40][41][42][43][44] and 54% (49-59) at 2 years for patients with Crohn's disease, whereas the relapse rate for patients with ulcerative colitis or IBD unclassified was 35% (26-43) at 1 year and 42% (27-58) at 2 years. 46 A separate systematic review and meta-analysis produced similar results, with the overall risk of relapse after anti-TNF discontinuation being 44% in patients with Crohn's disease and 38% in those with ulcerative colitis.…”

A Review on the Use of Anti-TNF in Children and Adolescents with Inflammatory Bowel Disease

“…Thirty-eight percent of patients needed IFX dose increase after withdrawal of the immunomodulator and 18% discontinued IFX [74]. The same authors showed that for similar effectiveness, combination therapy reduces IFX drug consumption and that IFX doses need to be increased upon discontinuation of the immunomodulator [75].…”

Biologic therapies for Crohn’s disease: optimising the old and maximising the new

“…More recently, a post-hoc analysis of the SONIC trial suggested that the benefit of adding azathioprine to IFX could be explained solely by the resulting increment in IFX serum concentrations rather than the additive immunosuppressive effect of azathioprine 27 . In keeping with this, a subsequent prospective study observed that optimised IFX monotherapy is as effective as optimised combination therapy 28 . However, the IFX monotherapy group required significantly higher rates of treatment escalation, which makes this strategy unfavourable on a cost-effectiveness basis.…”