270
3 mg/kg for RA in conjunction with methotrexate 12.5–25 mg weekly. Of note, RA
patients tend to have lower rates of anti-drug antibody development presumably due to
the use of concomitant methotrexate compared to other disease states such as psoriasis
and IBD, which tend to have higher rates of immunogenicity [ 22 – 25 ]. In accordance to
recommendations by the World Health Organization (WHO) and the Food and Drug
Administration (FDA), in order to extrapolate across indications with efficacy and
safety data, immunogenicity risk should be studied in the highest risk patient popula-
tion for therapy-related adverse events and anti-drug antibody potential [ 26 , 27 ]. Thus,
further investigation with respect to the clinical efficacy and pharmacokinetics of
CT-P13 in the moderate to severe IBD patient population may be valuable to add insight
to the true bioequivalence in this different immune- mediated disease state [ 28 , 29 ].
TheNOR-SWITCH study is a randomized, double-blind, parallel-group study of
155 CD and 93 UC patients to evaluate the efficacy and safety of switching from
Remicade® to the biosimilar across several disease states including CD and UC
[ 30 ]. After being in a sustained remission for at least 24 weeks on stable dosing of
reference infliximab, patients were randomized to continuing the originator inflix-
imab versus switching to CT-P13. The primary endpoint was disease worsening at
week 52 defined as an increase in partial Mayo score of at least 3 points with a mini-
mum score of 5 for UC patients and an increase in the Harvey-Bradshaw Index
(HBI) score of at least 4 points with a minimum score of 7 for CD patients.
Secondary study endpoints included safety and immunogenicity [ 30 ].
For CD patients continuing reference infliximab, 21% of patients experienced dis-
ease worsening, compared to 37% of patients switching to CT-P13 (95% CI −29.3%,
−0.7%). For UC patients, 9% of patients continuing reference infliximab had disease
worsening, compared to 12% of patients who switched to CT-P13 (95% CI−15.2%,
−10.0%). There were no statistically significantdifferences for PK drug trough levels-
between reference drug and CT-P13 for either UC or CD patients. Notably, anti-drug
antibodies, adverse events, and serious adverse eventswere similar in both groups.
While the strengths of the study included the RCT design, dosing according to standard
protocols, and finance of the study by the Norway federal government, limitationswere
thatthe study was not powered for non-inferiority within each diagnostic group [ 30 ].
There are also two prospective observational studies for CT-P13 in IBD:
NCT02539368, CONNECT-IBD, a post-marketing observational cohort of
CT-P13 in clinical practice to assess safety, immunogenicity, sustained efficacy, and
patient-reported outcomes sponsored by Hospira, and NCT02326155, another
observational prospective cohort study of CT-P13 sponsored by Celltrion, the two
currently available manufacturers of the infliximab biosimilar [ 31 – 33 ].
Extrapolation
Extrapolation refers to the approval of an approved biosimilar for a condition in
which it was not clinically studied, and it is one of the most controversial issues
regarding adoption of biosimilars in those countries for which it is approved. The
C.Y. Ha and A. Kornbluth