Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study

Abstract

Background: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs).

Methods: This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed.

Results: Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions.

Conclusions: CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed.

Trial registration: ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.

Figures

Fig. 1

Flowchart of patient disposition. A total of 250 eligible patients were randomized into the CT-P13 group (n = 125) or RP group (n = 125) to receive 5 mg/kg of CT-P13 or RP, respectively. All 250 randomly assigned patients were included in the intention-to-treat population. *One patient randomly assigned to RP received at least one dose of CT-P13 unintentionally. RP reference product (i.e., reference infliximab)

Fig. 2

Proportion of patients with an ASAS20 response, ASAS40 response and ASAS PR* up to week 54 by treatment in the a ITT population (MEX approach) and b ITT population (LOCF approach). “n = numbers” in the bar represent the denominator of patients assessed at each time point. *PR was defined as a value of <20 on a 0–100 scale in each of the following four domains: patient global assessment, pain, function, and inflammation. ASAS Assessment of Spondylo Arthritis international Society (ASAS20 and ASAS40, 20 % and 40 % response according to the ASAS International Working Group criteria for improvement), ITT intention-to-treat, LOCF last observation carried forward, MEX missing equals excluded, PR partial remission, RP reference product (i.e. reference infliximab)

Fig. 3

Mean a BASDAI, b BASFI, c SF-36 Physical Component Summary, d SF-36 Mental Component Summary and e BASMI scores up to week 54 by treatment. BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, BASMI Bath Ankylosing Spondylitis Metrology Index, RP reference product (i.e. reference infliximab), SF-36 Short Form (36) Health Survey, SE standard error

Fig. 4

Mean (SD) serum PK parameters of CT-P13 and RP (PK population). Note: values below the LLOQ have been set equal to the LLOQ. LLOQ lower limit of quantification, PK pharmacokinetics, RP reference product (i.e. reference infliximab), SD standard deviation

Fig. 5

Primary PK parameters (Cmax,ss and AUCτ) by ADA titer level at week 30 (PK population). Note: titer levels were defined as low, medium and high titer based on tertile grouping of the data. ADA anti-drug antibodies, AUCτ area under the concentration time curve over the dosing interval, at steady state between week 22 and week 30, Cmax,ss the observed maximum serum concentration at steady state between week 22 and week 30, PK pharmacokinetics, RP reference product (i.e. reference infliximab)