Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis

Abstract

Objective: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA.

Methods: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity.

Results: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive.

Conclusion: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17.

Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.

Keywords: CT-P17; adalimumab; biosimilar; efficacy; immunogenicity; rheumatoid arthritis; safety; switching; tumour necrosis factor inhibitors.

Fig. 1

Study design ^aRandomization prior to week 0 study drug administration; details of randomization methods including stratification factors have been published previously (Kay et al., Arthritis Res Ther 2021;23:51). ^bSubjects received 40 mg (100 mg/ml) CT-P17 or reference adalimumab, as shown, every 2 weeks with concomitant methotrexate and folic acid (Kay et al., Arthritis Res Ther 2021;23:51). ^cRandomization prior to week 26 study drug administration was stratified by disease activity per SDAI at week 24, in terms of remission (SDAI ≤3.3) versus non-remission (SDAI >3.3). EOS: end-of-study; R: randomization; SDAI: Simplified Disease Activity Index.

Fig. 2

Subject disposition (intention-to-treat population) Figure adapted from Kay et al. (Arthritis Res Ther 2021;23:51) as permitted under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). ^aSubject discontinued CT-P17 treatment because of significant dose delay due to adverse event. ^bTwo subjects discontinued reference adalimumab treatment because of subject decision due to adverse event. ^cDenominator is the number of subjects assigned to the treatment group in the first randomization. ^dAll subjects receiving CT-P17 during treatment period 1 continued to receive CT-P17 during treatment period 2 following a mock randomization process to maintain the study blind. ^eOne subject randomized to switch to CT-P17 did not initiate study drug in treatment period 2 due to adverse event. ^fOne subject discontinued CT-P17 treatment because of significant dose delay due to adverse event and two subjects discontinued as they were unable to visit the study site due to the COVID-19 pandemic. ^gOne subject discontinued reference adalimumab as they were unable to visit the study site due to the COVID-19 pandemic. ^hDenominator is the number of subjects assigned to the treatment group in the second randomization. COVID-19: coronavirus disease 2019.

Fig. 3

Clinical efficacy during treatment period 2 (intention-to-treat population—treatment period 2 subset) (A) ACR response rates at week 52; (B) Mean change from baseline in DAS28-CRP value during treatment period 2; (C) Mean change from baseline in CDAI value during treatment period 2; (D) Mean change from baseline in SDAI value during treatment period 2; (E) EULAR-CRP response rates at week 52. ACR20/50/70: 20%/50%/70% improvement according to ACR criteria; CDAI: Clinical Disease Activity Index; DAS28-CRP: Disease Activity Score in 28 joints–CRP; SDAI: Simplified Disease Activity Index.