Background: Aims of the present study were to compare clinical outcomes and IFX pharmacokinetics between patients treated with IFX in monotherapy vs those in combination therapy with IS (azathioprine, methotrexate) for at least three months, and to isolate the most effective duration of this combination in terms of clinical and pharmacological outcomes.
Methods: All IBD patients treated with IFX from January 2012 to January 2016 were retrospectively included. Activity disease and TLI were measured before each IFX infusion, using clinical validated scores (Crohn's disease: Harvey-bradshaw index; ulcerative colitis: Mayo clinic), and immunoassay (Theradiag®), respectively. A prior monotherapy with IS was not an exclusion criterion. Patients under combotherapy less than 14 weeks were excluded. An unfavorable pharmacokinetic was defined as a TLI<1μg/mL during the follow-up period, regardless the presence or absence of antibodies anti-Infliximab. Kaplan Meier method and univariate Cox proportional hazard regression were performed to assess clinical relapse free survival and unfavorable IFX pharmacokinetics free survival.
Results: Of the 139 patients included (median age: 34 yrs, sex ratio M/F: 1/3; median follow-up: 40 months), 60 (43%) were under combination therapy during a median time of 11 months. There was no difference in terms of clinical characteristics at baseline between the two groups (mono- vs combotherapy with IFX). The median clinical relapse free survival was higher in the combination therapy group (>80 months) compared to the group of monotherapy (30 months; HR=2.73 CI 95% 1.62–4.6, p=0.001). However, none optimal duration of combination therapy was identified by univariate Cox regression (p>0.05 for 3, 6, 9, 12 and 18 months, as cut-off). There was no difference between naïve patients and those previously treated with IS in terms of clinical relapse free survival and unfavorable IFX pharmacokinetics free survival. By an independent analysis, the proportion of trimesters with TLI<1μg/mL was lower under combination therapy (3.8%) compared to monotherapy (11.8%; (p<0.001).
Conclusions: This retrospective study confirmed that combination therapy with IFX and IS improves clinical free survival compared to monotherapy, in unselected IBD patients. However, there was no demonstrated benefit for the maintenance of this combination over three months, despite it seems that unfavourable IFX pharmacokinetic occurs when IS are withdrawn early. Prior treatment with IS appears not to impact on these outcomes.