This randomised, double-blind, multicentre and multinational, parallel-group, prospective PLANETAS study assessed the PK equivalence and safety and efficacy comparability of multiple doses of CT-P13 (5 mg/kg) versus INX (5 mg/kg) administered up to week 30 in active AS patients.
The primary outcome, steady-state PK (AUC and Cmax,ss
), was shown to be equivalent for CT-P13 and INX (90% CIs for the mean AUC and Cmax,ss
were 94–116% and 95–109%, respectively). These values were within the predefined margins for equivalence (80–125%), thereby satisfying the criteria set for PK equivalence of CT-P13 to INX. This predefined margin is considered appropriate from a clinical perspective because of the broad therapeutic window and high variability of INX.18
AUC and Cmax,ss
were higher in the ADA-negative subset of patients in this study, versus values for the overall PK population. Published PK data for the 5mg/kg dose of INX in AS is sparse,20
but the values for AUC and Cmax,ss
reported in this study are similar to those reported in previous studies of INX monotherapy using a similar dosing pattern in Crohn's disease.21
The coadministration of methotrexate (MTX) is thought to increase concentrations of INX in patients with rheumatoid arthritis (RA).22–25
Although coadministration of MTX with INX in AS is not recommended,5
the effect of coadministration on CT-P13 should be further studied—especially in patients with peripheral arthritis. In patients with AS, the possible influence of ADA on circulating concentrations of INX, including the potential consequence, an impaired clinical response, has been studied but yielded conflicting results.26–28
Nevertheless, INX monotherapy remains a useful treatment for the majority of patients with AS, for which long-term data are available.29
The mean secondary PK endpoints were also highly similar between CT-P13 and INX groups. CT-P13 was also equivalent to INX up to week 30 in terms of efficacy as assessed by ASAS20/ASAS40 criteria. The median change from baseline in BASDAI, BASFI, BASMI, chest expansion and SF-36 score was highly similar at weeks 14 and 30, underlining the benefit of CT-P13 and INX in both physician-measured and patient-reported outcomes.
The efficacy outcomes of this trial were comparable to those reported previously in pivotal randomised controlled trials of INX in AS.1
The ASAS20 and ASAS40 responses at week 30 in this study for INX (72.4% and 47.4%, respectively) are similar to those reported at week 24 in the ASSERT trial (61.2% and 47.0%, respectively). The magnitude of improvements in secondary efficacy endpoints with INX in this trial were also comparable to those reported in ASSERT.2
Improvements from baseline to week 30 of the physical component of the SF-36 in the INX group in this study were comparable to those reported in ASSERT (8.5 vs 10.2, respectively), as were the median baseline scores of the physical component of the SF-36 (28.8 vs 33.1, respectively).2
However, the improvements from baseline to week 30 of the mental component of the SF-36 in this study were not seen in ASSERT (5.2 vs 2.7, respectively), likely reflecting the higher baseline median scores of the mental component of SF-36 in ASSERT (37.2 vs 47.6, respectively).2
ASDAS C was assessed in this study, and values were found to be highly similar between treatment groups at both weeks 14 and 30.31
Comparison of ASAS20 and ASAS40 values for CT-P13 and INX by ADA status showed no statistical significance despite the observational difference in the ADA-positive subset, the latter probably due to the lack of patient numbers.
Overall, CT-P13 and INX were well-tolerated and their safety profiles were comparable. The majority of patients had negative immunogenicity results according to the electrochemiluminescent immunoassay method at weeks 14 and 30. Extra-articular manifestations such as uveitis, psoriasis and inflammatory bowel disease were not assessed in this study, but the single cases of uveitis and psoriasis in the INX group were reported as AEs. The incidence of AEs, SAEs, infections and infusion-related reactions with INX in this trial were comparable to that seen in ASSERT.2
There were also comparably low rates of TB up to week 30. The incidence of TB in our study (1.2% overall: CT-P13 (n=2), INX group (n=1)) is higher than in ASSERT, a trial of INX in AS, in which no cases were reported during the study period.2
A difference in the study site locations may partly explain this; ASSERT included only centres in North America and Western Europe, whereas our trial included centres in countries known to have higher TB incidence. Interestingly, the incidence of active TB in our study is similar to those of the two major trials of the 3 mg/kg dose of INX in RA, Anti-TNF Trial inRheumatoid Arthritis with Concomitant Therapy (ATTRACT) (0.3%) and Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) (0.5%), which included centres only in North America and Western Europe.18
According to the National Institute of Health and Clinical Excellence (NICE) incremental cost-effectiveness ratios (ICERs), INX has not been recommended for treatment of AS because NICE experts did not consider it to be cost-effective. However, this decision should be revisited based on the results of this study of CT-P13 in AS and its lower future price. This may have a potentially positive impact on healthcare costs.
In this PLANETAS study, PK equivalence for CT-P13 and INX was demonstrated. There was no significant difference in efficacy and safety data. Although only comparable clinical efficacy was shown in this study, clinical bioequivalence was investigated in a Phase 3 study in RA.8
The positive results of this study provide a rationale for future studies of CT-P13 in the treatment of other TNF-mediated inflammatory diseases.