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.