Switching standard dosed intravenous to subcutaneous infliximab leads to similar drug exposure in inflammatory bowel disease patients independent of concomitant immunosuppressants (SHUFFLE study).

AIMS: Subcutaneous (SC) flat-dose infliximab (IFX) biosimilar offers potential advantages over intravenous (IV) weight-based dosing. Prospective pharmacokinetic data and clinical outcomes in inflammatory bowel disease (IBD) are scarce, since drug approval was primarily based on a rheumatoid-arthritis study population concomitantly using methotrexate. We aim to compare IFX exposure during IV and SC therapy in IBD patients and address the effect of concomitant immunosuppressants. METHODS: In this single-centre, prospective study, adult IBD patients in clinical remission on a 6-8 weekly IFX IV-dosing interval were switched to biweekly SC IFX and followed for 24 weeks. Primary endpoint was the area under the concentration-time curves (AUCs). Secondary endpoints included trough levels, time burden and quality-of-life (inflammatory bowel disease questionnaire [IBDQ-NL]). As an additional follow-up assessment, trough levels at ≥12 months were compared across IFX mono-, combination- and immunosuppressant discontinuation groups. RESULTS: Thirty-five patients were evaluated: 20 received IFX monotherapy and 15 IFX combination therapy. Mean AUCs6-8 weeks were comparable between IV and SC administration, independent of immune suppressive. IFX trough levels increased on SC IFX median 4.6 mg/L vs.16.1 mg/L (p < 0.05), independent of concomitant immunosuppressants. These results were consistent at ≥12 months, regardless of monotherapy, combination therapy or immunosuppressant discontinuation. Time burden decreased substantially (median -9.3 h/6 months, p < 0.05), and IBDQ-NL score increased (189-197, p < 0.05). There were no exacerbations during follow-up. After 24 weeks, 97% were still being treated with IFX SC. CONCLUSIONS: SC IFX in IBD patients maintained equivalent drug exposure with higher trough levels, reduced time burden and stable quality-of-life, independent of concomitant immunosuppressants.