Biosimilar CT-P13 noninferior to infliximab for Crohn's Disease
The latest phase III randomized trial showed that infliximab biosimilar CT-P13 was noninferior to its reference product in patients with active Crohn’s disease (CD), providing the first high-level evidence on the equivalence of efficacy between the two for a non-rheumatological indication.
“Approval of CT-P13 by the EMA* and FDA**, including for CD, was based on extrapolation of data … in patients with rheumatoid arthritis and ankylosing spondylitis. Thus, CT-P13 was not specifically tested in patients with inflammatory bowel disease [IBD] before approval,” the researchers pointed out.
“Extrapolation of approval to non-studied indications has led to considerable debate, not least because it assumes that the mechanisms of action for inﬂiximab are similar between indications,” they added. “[Our study is] the first phase III randomized controlled trial [RCT] to provide confirmatory evidence on the validity of the extrapolation process for an infliximab biosimilar in IBD.”
Similar proportion of patients achieved the primary endpoint of a ≥70 points decrease in CDAI*** (CDAI-70) at week 6 among those who initiated CT-P13 and those who initiated infliximab (69.4 percent vs 74.3 percent, difference, -4.9 percent, 95 percent confidence [CI], -16.9 to 7.3), which met the prespecified noninferiority criteria of a value greater than -20 in the lower limit of the CI. [Lancet 2019;393:1699-1707]
Similar results were seen for CDAI-70 response at weeks 14 and 30.
There were also no significant differences between the two groups in clinical response based on CDAI-100 and in clinical remission rates (indicated by CDAI <150) at weeks 6, 14, and 30, or post-switching at 54 weeks.
The multicentre, double-blind, phase III noninferiority trial randomized 220 anti-TNF-naïve patients with active CD who were refractory or intolerant to nonbiological treatments in a 1:1 ratio to receive CT-P13 at 5 mg/kg dose or infliximab at weeks 0, 2, 6, followed by a Q8W regimen up to week 54. At week 30, patients in each arm were further randomized to continue with the initial treatment or switch to the other arm.
“Efficacy was well maintained and similar between groups after switching,” stated the researchers, noting that clinical response and remission rates were comparable between both groups up to week 54.
Similarly, steroid-free remission rates were not significantly different between treatments at week 30 (45.9 percent vs 50.5 percent for CT-P13 and infliximab, respectively), which were sustained after switching.
“These findings add to growing real-world evidence collected in patients with IBD,” the researchers said.
However, they also cautioned that the study was not powered for noninferiority of switching after 30 weeks.
Both treatments were well tolerated, the researchers noted. The proportions of patients who had ≥1 treatment-emergent adverse event (TRAE; 62–73 percent), incidence of TRAEs leading to discontinuation, and treatment-emergent (TE) serious AEs were broadly similar between the two arms. The rates of infection-related TEAEs were also similar between groups before and after switching.
In addition, the proportion of patients who developed antidrug antibodies (39 percent vs 45 percent) or neutralising antibodies (20 percent vs 19 percent) were comparable between the two treatments.
“The costs of anti-TNF and other biological drugs are often high, placing a financial burden on healthcare systems and sometimes limiting access to these drugs,” the researchers pointed out, suggesting that biosimilars such as CT-P13 may be the answer to this concern.
“The findings should assist clinicians in their decision making when starting a patient on anti-TNF treatment,” they added.