Comparative efficacy of subcutaneous (CT-P13) and intravenous infliximab in adult patients with rheumatoid arthritis: a network meta-regression of individual patient data from two randomised trials

Abstract

Background: A subcutaneous (SC) formulation of infliximab biosimilar CT-P13 is approved in Europe for the treatment of adult patients with rheumatoid arthritis (RA). It may offer improved efficacy versus intravenous (IV) infliximab formulations.

Methods: A network meta-regression was conducted using individual patient data from two randomised trials in patients with RA, which compared CT-P13 SC with CT-P13 IV, and CT-P13 IV with reference infliximab IV. In this analysis, CT-P13 SC was compared with CT-P13 IV, reference infliximab IV and pooled data for both reference infliximab IV and CT-P13 IV. Outcomes included changes from baseline in 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and rates of remission, low disease activity or clinically meaningful improvement in functional disability per Health Assessment Questionnaire-Disability Index (HAQ-DI).

Results: The two studies enrolled 949 patients with RA; pooled data for 840 and 751 patients were evaluable at weeks 30 and 54, respectively. For the CT-P13 SC versus pooled IV treatment arm comparison, differences in changes from baseline in DAS28-CRP (- 0.578; 95% confidence interval [CI] - 0.831, - 0.325; p < 0.0001), CDAI (- 3.502; 95% CI - 5.715, - 1.289; p = 0.002) and SDAI (- 4.031; 95% CI - 6.385, - 1.677; p = 0.0008) scores at 30 weeks were statistically significant in favour of CT-P13 SC. From weeks 30 to 54, the magnitude of the differences increased and remained statistically significant in favour of CT-P13 SC. Similar results were observed for the comparison of CT-P13 SC with CT-P13 IV and with reference infliximab IV. Statistically significant differences at week 30 favoured CT-P13 SC over the pooled IV treatment arms for the proportions of patients achieving EULAR-CRP good response, American College of Rheumatology (ACR) 50 and ACR70 responses, DAS28-CRP-defined remission, low disease activity (DAS28-CRP, CDAI and SDAI criteria) and clinically meaningful HAQ-DI improvement.

Conclusions: CT-P13 SC was associated with greater improvements in DAS28-CRP, CDAI and SDAI scores and higher rates of clinical response, low disease activity and clinically meaningful improvement in functional disability, compared with CT-P13 IV and reference infliximab IV.

Trial registration: EudraCT, 2016-002125-11 , registered 1 July 2016; EudraCT 2010-018646-31 , registered 23 June 2010.

Keywords: CT-P13; Disease activity; Indirect treatment comparison; Individual patient data; Infliximab; Intravenous; Network meta-regression; Rheumatoid arthritis; Subcutaneous; Tumour necrosis factor inhibitor.

Fig. 1

Imputation of week-54 CT-P13 3.5 results based on CT-P13 regression model. EU, European Union; IV, intravenous; MTX, methotrexate; PD, pharmacodynamics; PK, pharmacokinetics

Fig. 2

Change from baseline in DAS28-CRP (a), CDAI (b) and SDAI (c) at weeks 30/54. CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28-CRP, 28-joint Disease Activity Score based on C-reactive protein; IV, intravenous; SDAI, Simple Disease Activity Index; SC, subcutaneous; SD, standard deviation. *CT-P13 IV vs CT-P13 SC p < 0.05, CT-P13 SC vs reference infliximab IV p < 0.05 and CT-P13 IV vs reference infliximab IV p ≥ 0.05. p-values derive from the meta-regression efficacy analysis of week-30 and week-54 data (Tables 3 and 4)