Subcutaneous Versus Intravenous Infliximab Therapy: Toward Higher Drug Concentrations

Background: Subcutaneous infliximab (SC-IFX) has been associated with a more favorable pharmacokinetic profile than intravenous infliximab (IV-IFX) in patients with inflammatory bowel disease (IBD). The aim of this study was to compare infliximab serum concentrations in patients with IBD, before and after the switch from IV-IFX to SC-IFX, with a minimum follow-up of 6 months. Methods: Retrospective single-center study including patients with Crohn’s disease (CD) and ulcerative colitis (UC) in clinical remission, previously medicated with IV-IFX, who switched to SC-IFX. In CD, clinical remission was considered as a Harvey-Bradshaw index of 4 or less points and, in UC, as the absence of symptoms. Biochemical parameters were evaluated before the switch to SC-IFX and 6 months after, and included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), faecal calprotectin, infliximab serum concentrations and the presence of antibodies to infliximab (ATI). Results: A total of 40 patients were included, 32 with CD (80.0%) and 8 with UC (20.0%). Most patients were male (57.5%), with a median age of 34 years and a median disease duration of 9.5 years. In CD patients, 16 patients had ileal disease (50.0%), 3 colonic (9.4%) and 13 ileocolonic disease (40.6%); 19 patients had nonstricturing, nonpenetrating disease (59.4%), 7 stricturing (21.9%) and 6 penetrating disease (18.7%). Nine patients had perianal disease (28.1%) and three had been previously submitted to CD-related surgery. Regarding UC, 4 patients had left-sided colitis (50.0%) and 4 patients had extensive colitis (50.0%). The mean infliximab serum concentrations were significantly higher after 6 months of SC-IFX, compared to before the switch (17.3±6.8 µg/mL vs 9.6±5.6 µg/mL, P< 0.001). No association was found between the increase in infliximab serum concentrations after the switch to SC-IFX and the patients’ sex (mean female 10.0±9.0 µg/mL vs male 8.2±5.7 µg/mL, p=0.481), age (p=0.744), disease (mean DC 9.2±6.9 µg/mL vs UC 8.3±9.2 µg/mL, p=0.774), disease duration (p=0.651), and immunomodulatory therapy (mean with immunomodulatory therapy 9.1±7.6 µg/mL vs without 8.9±7.2 µg/mL, p=0.957). No patient developed ATI and only 2 patients had adverse effects (5%), namely skin rash at the administration site. All patients were initially in clinical remission and stayed clinically stable for the 6 months after the switch from IV-IFX to SC-IFX. No differences were found between ESR, CRP and faecal calprotectin, before and after the switch to SC-IFX (ESR: median 7.0 vs after 7.0 mm, p=0.735; CRP: median before 0.8 mg/L vs after 1.6 mg/L, p=0.247; faecal calprotectin: median before 62 µg/g vs after 83 µg/g, p=0.923). Conclusions: The switch from IV-IFX to SC-IFX is effective and well tolerated in IBD patients in clinical and biochemical remission, with an increased systemic drug concentration, regardless of the combination with immunomodulatory therapy.