P930 Rapid symptomatic improvement with subcutaneous infliximab induction treatment for patients with moderate-to-severe Crohn’s disease: first results from the DIRECT-CD study

Abstract

Abstract Background Subcutaneous (SC) formulation of infliximab (IFX) received regulatory approval for the maintenance treatment of Crohn’s disease (CD) in 2020. DIRECT-CD is an ongoing multicentre trial to evaluate the efficacy of SC IFX induction and maintenance treatment in monotherapy versus combination therapy in CD (EUDRACT 2021-000469-33). Here we aimed to determine the rapidity of symptom improvement during this SC IFX induction regimen. Methods Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) >220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at Week 0 and 2, followed by maintenance treatment (120 mg every other week). We analysed diary PRO-2 entries (stool frequency and abdominal pain) through 14 days from the first injections of SC IFX. CDAI was assessed at Week 0, 2, 4 and 8. Changes in biochemical parameters were assessed (C-reactive protein [CRP]: Week 4 and 8; faecal calprotectin [FC] at Week 8). Combined corticosteroid-free remission (CSFR) was defined as CDAI<150 and CRP≤5 mg/L or FC≤250 mg/kg and complete tapering of corticosteroids. Results Twenty-five patients completed 8 weeks of treatment (60% female, median age 30 years [IQR 24-45], median weight 66.6 kg [IQR 64.0-89.5], median disease duration 4 years [IQR 1-8], 64% had ileocolonic disease [L3] and 76% exhibited an inflammatory phenotype [B1], 52% were using concomitant immunomodulators, and 28% were on stable dose of steroids). On the first day after the initial dose of SC IFX (240 mg), a significant decrease in PRO-2 was observed compared to baseline (5 [IQR 3-9] vs 8 [IQR 7-10], P<0.001) and this response was sustained throughout day 14 (P<0.001, Figure 1). At all measured time points, CDAI decreased significantly compared to baseline (Week 0: 313 [IQR 271-402]; Week 2: 245 [IQR 140-296], P<0.001; Week 4: 218 [101-258], P<0.001; Week 8: 172 [127-260], P<0.001). Combined CSFR was reached in 30% and 57% of all patients at Week 4 and 8, respectively. Median CRP was lower at Week 4 compared to baseline CRP (2.8 mg/L [IQR 0.7-4.9] vs 7.1 mg/L [IQR 2.1-26.3], P=0.001), a significant drop of FC was observed at Week 8 compared to baseline (77 mg/kg [IQR 37-847] vs 1385 mg/kg [IQR 219-3093], P<0.001). Conclusion Induction treatment with SC IFX provided a rapid decrease of abdominal pain and diarrhoea as early as day one. CDAI, CRP and FC decreased significantly at the earliest time point of evaluation (Week 2-8). DIRECT-CD is an ongoing clinical trial.