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LAS VEGAS -- In patients with inflammatory bowel disease who lost response after infliximab (Remicade) induction, escalating the maintenance dose of the subcutaneous infliximab biosimilar CT-P13 improved clinical response and remission, without new safety concerns, according to a post-hoc analysis of a randomized controlled study.

In dose-escalated patients, clinical response was 49.4% in those with ulcerative colitis and 61.5% in those with Crohn's disease, while clinical remission rates were 24.7% and 53.8%, respectively, reported Silvio Danese, MD, PhD, of the IRCCS San Raffaele Hospital in Milan, at the Crohn's & Colitis Congress.

Furthermore, 28.2% of Crohn's patients had endoscopic responses and 12.8% had endoscopic remission, while 30.2% of ulcerative colitis and 31.8% of Crohn's patients achieved corticosteroid-free remission, and 22.2% of ulcerative colitis patients had endoscopic-histologic mucosal improvement.

Sara Horst, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in this research, said the findings were important and helpful given the value of CT-P13 dose escalation.

"We know that in patients with inflammatory bowel disease, using infliximab reference or biosimilar dose escalation can be a useful strategy to improve likelihood of clinical response or remission," Horst said. In this study, "patients who required dose escalation had lower drug concentrations than those who did not require dose escalation. Someone with continued symptoms and lower levels may need dose escalation of CT-P13, very similarly to what we do for infliximab. These are important data and add to our understanding of how to use this new medication."

The researchers analyzed data from the LIBERTY-UC and LIBERTY-CD trials, simultaneous randomized controlled trials that evaluated maintenance therapy with the infliximab biosimilar CT-P13 over 54 weeks in patients with moderately to severely active ulcerative colitis and Crohn's disease. The trials included 294 patients with ulcerative colitis (median age 37-38, 54-56% men) and 231 with Crohn's disease (median age 36, 58-59% men) who received three 5 mg/kg-doses of intravenous infliximab as induction therapy.

At week 10, clinical responders randomly received either subcutaneous CT-P13 120 mg or placebo as maintenance therapy every 2 weeks. At week 22, any participants who had initially responded but lost response could escalate the CT-P13 dose to 240 mg every 2 weeks.

For ulcerative colitis patients, the researchers defined loss of response as having a Modified Mayo Score (MMS) increase of at least 2 points and at least 30% from the week-10 MMS, with a total MMS of at least 5 and an endoscopic subscore of at least 2. In Crohn's patients, loss of response was defined as an increase in the Crohn's Disease Activity Index (CDAI) of at least 100 points from the week-10 CDAI score, with a total score of at least 220.

Dose escalation occurred more often among ulcerative colitis patients (27.6%) than among Crohn's patients (16.9%) during the trial's 54 weeks. Among the patients who received a dose escalation, 74.1% of ulcerative colitis patients and 51.3% of Crohn's patients received it at week 22, the first time it became available in the trial. Overall mean time to dose escalation was 25.6 weeks in the ulcerative colitis group and 29.8 weeks in the Crohn's group.

Among dose-escalated patients, the MMS score in ulcerative colitis patients fell from 5.8 prior to escalation to 3.4 at week 54 (P<0.0001), and the CDAI score in Crohn's patients fell from 256.4 before escalation to 105.4 at week 54 (P<0.0001). The drop in Crohn's patients' simplified endoscopic activity score from 7.8 before escalation to 6.5 at week 54 was non-significant (P=0.1237).

Rates of treatment-emergent adverse events (TEAEs) were similar during the maintenance period for patients who did (72.3%) and did not (68.8%) receive dose escalation, as were severe TEAEs: 5.8% in combined IBD patients with dose escalation and 6.8% in those without escalation. Infections occurred in 29.9% of dose-escalated patients and 29.2% of non-dose-escalated patients.

In terms of immunogenicity, 59.8% of dose-escalated patients and 65.9% of non-dose-escalated patients showed a positive conversion in anti-drug antibody.

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