Issue 16

Clinical Question

How feasible is it to switch from infliximab (IFX) to its biosimilar, CT-P13, and how do we prognosticate a patient’s response?

Editor’s Bottom Line

Switching from the innovator infliximab to a biosimilar appears to be well tolerated, although a control group continued on the innovator would have been a useful comparator. Therapeutic drug monitoring may have prognostic value when starting an infliximab biosimilar.

References

Buer LC, Moum BA, Cvancarova M, et al. Switching from Remicade® to Remsima® is well tolerated and feasible: a prospective, open-label study. J Crohns Colitis. 2017 Mar 1;11(3):297–304. https://www.ncbi.nlm.nih.gov/pubmed/27660339

Gonczi L, Vegh Z, Golovics PA, et al. Prediction of short- and medium-term efficacy of biosimilar infliximab therapy. Do trough levels and antidrug antibody levels or clinical and biochemical markers play the more important role? J Crohns Colitis. 2017 Jun 1;11(6):697–705. https://www.ncbi.nlm.nih.gov/pubmed/27838610

Synopsis

Buer et al.
All patients with IBD were switched from IFX to CT-P13, for cost reduction purposes, then prospectively followed for 6 months. A retrospective chart review compared drug dosing and disease activity (e.g., Harvey-Bradshaw Index, C-reactive protein (CRP), hemoglobin, fecal calprotectin) between the last 6 months of IFX and CT-P13. The primary study endpoint was the portion of patients still on the biosimilar after 6 months and adverse events.

Of the 143 patients (CD, n=99; UC, n=44), 17 had adverse events and 97% continued taking CT-P13 after 6 months. No changes were observed in dosing, frequency, and measures of disease activity. Three patients developed anti-drug antibodies (ADAs) while taking the biosimilar.

Gonczi et al.
Eligible patients were not exposed to IFX in the 12 months prior to starting CT-P13. At weeks 0, 14, 30, and 54, disease activity (CDAI or partial Mayo score) was recorded and blood was drawn to measure CRP, total blood count, trough levels, and ADAs. Disease location and history were retrieved from patient charts. At weeks 2 and 6, a receiver operating characteristics (ROC) analysis of trough levels identified cut-offs for CT-P13 trough levels associated with clinical response* or remission** at weeks 14, 30, and 54.

A total of 291 patients (CD, n=184; UC, n=107) were enrolled and had mean trough levels of 20.1, 14.7, and 5.1 μg/ml at weeks 2, 6, and 14. For CD, trough levels measured at week 2 predicted only response or remission at week 14 (AUC=0.715–0.721). In patients with UC, week 2 trough levels predicted clinical response and remission at week 14 (AUC=0.81 and 0.79, respectively) and week 30 (AUC=0.79 and 0.74, respectively). In UC, patients who tested positive for ADAs at week 14 had a decreased chance of clinical response at week 30.

* Response: CDAI decreased by ≥70 or 50% reduction in number of draining fistula; partial Mayo score decreased by >3
** Remission: CDAI<150 and no fistula drainage; partial Mayo<3

Details

Buer et al.
Study Design: Prospective open-label study
Funding: None
Allocation: n/a
Setting: Single centre, Norway
Level of Evidence: 2b (Oxford Levels of Evidence)

Gonczi et al.
Study Design: Prospective observational cohort study
Funding: Hungarian Scientific Research Fund
Allocation: n/a
Setting: 12 IBD centres in Hungary
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.