At week 54, there were no significant differences in patients achieving the target exposure (5 µg/mL) between those in the monotherapy cohort and those in the combination therapy cohort.
The pharmacokinetics, immunogenicity, and efficacy were potentially comparable in biologic-naïve patients with inflammatory bowel disease (IBD) receiving subcutaneous infliximab monotherapy or in combination with immunosuppressants, according to a study published in Springer.1
Infliximab, a tumor necrosis factor inhibitor (TNF), is recommended as the first- or second-line biologic therapy for patients with IBD and can be used in combination with immunosuppressants, including methotrexate and azathioprine. The intravenous version of infliximab received along with concomitant immunosuppressants has been linked to improve outcomes when compared with monotherapy alone.2
“Whether the advantages of combining an immunosuppressant with intravenous infliximab are also true for combination therapy with subcutaneous infliximab and immunosuppressants has not hitherto been addressed,” wrote Geert D’Haens, PhD, Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, The Netherlands, and colleagues.
Biologic-naïve adult patients with active Crohn’s disease (CD) or ulcerative colitis (UC) were included in the post hoc analysis of an open-label, randomized, multicenter, phase 1 trial that compared subcutaneous infliximab monotherapy with combination therapy. Besides the previously mentioned criteria, eligible patients had a disease duration of ≥3 months and had not responded to an adequate course of conventional therapy.
Patients received intravenous CT-P13 5 mg/kg at week 0 and 2 during the “dose-loading phase.” At week 6, patients were randomized to receive subcutaneous CT-P13 120 or 240 mg, depending on weight (<80 or ≥80 kg, respectively) every 2 weeks until week 54, or to continue CT-P13 intravenously every 8 weeks until switching to the subcutaneous cohort at week 30. The present post hoc analysis only included those who received subcutaneous CT-PI3 from week 6 onwards.
The primary endpoint, which was non-inferiority of trough serum concentrations, was evaluated at week 22. The pharmacokinetic, safety, efficacy, and immunogenicity outcomes were compared up to week 54 and were stratified by concomitant immunosuppressant use.
In total, 66 patients were randomized to receive subcutaneous CT-P13, with 37 receiving monotherapy and 29 patients placed in the combination therapy group. In the combination therapy cohort, most (99.6%) were prescribed thiopurines.
At week 54, there were no significant differences in patients achieving the target exposure (5 µg/mL) between those in the monotherapy cohort and those in the combination therapy cohort (96.6% vs 95.8%, respectively; P >.999). These results were also reflected in the proportion of patients receiving monotherapy or combination therapy meeting efficacy or biomarker outcomes, such as clinical remission (62.9% vs 74.1%; P = 0.418). Both the monotherapy and combination therapy groups had comparable immunogenicity as well, regarding anti-drug antibodies (ADAs; 65.5% vs 48.0%, respectively; P =.271) and neutralizing antibodies in ADA-positive patients (10.5% vs 16.7%, respectively; P = .630).
Investigators stated that the exploratory nature of the post hoc analyses, coupled with the modest sample size, may have hindered the findings. Further, as most patients were prescribed thiopurine, the results may be generalizable for patients who were receiving other immunosuppressants. To remedy this, other studies can attempt to enroll more patients receiving methotrexate as a part of infliximab combination therapy. Additionally, the study only included TNF-naïve patients, which may have limited generalizability as investigators noted that prior biologic exposure may be linked to reduced efficacy due to a development of immunogenicity.
Despite these limitations, investigators emphasized that the results of this study demonstrated insights into the safety, efficacy, immunogenicity, and pharmacokinetics of subcutaneous CT-P13 monotherapy compared with concomitant immunosuppressant therapy and encourage conducting larger comparative studies to confirm these results.