The investigational biosimilar drug CT-P13 proved to have equivalent efficacy and safety comparable to that of infliximab, the tumor necrosis factor–alpha inhibitor that it is manufactured to mimic.

The findings are based on data from a randomized, double-blind, multicenter trial of 606 patients with active rheumatoid arthritis who had inadequate response to methotrexate alone.

Dr. Dae Hyun Yoo of Hanyang University Hospital for Rheumatic Diseases in Seoul, South Korea, reported no difference in the percentage of patients who met American College of Rheumatology 20% improvement criteria (ACR20) at 30 weeks (60.9% for CT-P13 vs. 58.6% for infliximab), which was the primary outcome of the study. The 95% confidence intervals for CT-P13 (–6%-10%) and infliximab (–4%-12%) were within the prespecified range of plus or minus 15% for equivalency (Ann. Rheum. Dis. 2013;72:1613-20).

The overall number of patients who reported treatment-emergent adverse events was virtually the same in patients who took CT-P13 (181) or infliximab (183). The adverse events that were deemed to be related to the study medications also occurred in a similar number of CT-P13 (106) and infliximab (108) patients. Most of these were mild to moderate in intensity. The trial’s safety objective was to determine whether CT-P13 had safety that was comparable, not equivalent, to that of infliximab.

Biosimilar drugs are meant to be "highly similar, but not identical and not ‘bioidentical,’ to approved ‘reference agents,’ " the authors wrote. CT-P13 is an immunoglobulin G1 chimeric human-murine monoclonal antibody to tumor necrosis factor–alpha (TNF-alpha) that has an amino acid sequence identical to that of infliximab. It is produced in the same type of cell line as the one used to produce infliximab.

In this study, known as PLANETRA (Program evaLuating the Autoimmune Disease iNvEstigational Drug cT-p13 in RA Patients), the investigators enrolled patients according to the same criteria as those used in several other clinical trials with infliximab, including the ATTRACT study for which infliximab was approved for the treatment of RA. The results obtained with CT-P13 were similar to those of other RA trials with infliximab that had the same enrollment criteria. The trial was conducted at 100 centers in 19 countries in Europe, Asia, Latin America, and the Middle East.

Patients in the trial met the revised 1987 ACR classification criteria for at least 1 year prior to screening, and were required to have at least six swollen and at least six tender joints and at least two of the following: morning stiffness lasting 45 or more minutes; serum C-reactive protein (CRP) level greater than 2.0 mg/dL; and an erythrocyte sedimentation rate of greater than 28 mm/hour. They needed to meet those criteria despite taking methotrexate for at least 3 months on a stable dose of 12.5-25 mg/week for 4 or more weeks prior to screening. Patients were permitted to receive an equivalent of 10 mg prednisolone or less per day and NSAIDs, if they had received a stable dose for at least 4 weeks prior to screening.

Approximately 82% of the patients were female, and the median age of patients was 50 years at baseline. The patients received either study drug at a dose of 3 mg/kg infused over a 2-hour period at weeks 0, 2, and 6, and then every 8 weeks to week 30. The patients also received an antihistamine 30-60 minutes before the infusion, at the investigator’s discretion. Weekly methotrexate doses ranged from 12.5 mg to 25 mg. Patients also received 5 mg/week or more of folic acid.

Because the higher overall CRP level at baseline of the patients in the ATTRACT study could indicate that the PLANETRA cohort had less severe disease (3.1 mg/dL vs./ 1.9 mg/dL), Dr. Yoo and his associates conducted a post hoc sensitivity analysis of patients with baseline CRP greater than 2 mg/dL or 2 mg/dL or less. The results showed no difference in treatment response based on baseline CRP level.

The approximate 7.5% rate of infusion reactions noted in both in the CT-P13 and infliximab arms of the trial was lower than the 20% noted in the product label for infliximab, and antidrug antibody status did not appear to affect their incidence or response to the study drugs.

"Assessment of efficacy and safety of CT-P13 in patients with RA for up to 1 year is ongoing, and the positive results of this study provide a rationale for future studies of CT-P13 in the treatment of other TNF-mediated inflammatory diseases," the investigators wrote.

The study was sponsored by Celltrion. Many of the authors received research grants and/or consultancy fees and logistics support from the company. One author is a full-time employee of Celltrion, and another author declared receiving payment for lectures from the company.

jevans@frontlinemedcom.com

Biosimilar matches up well against infliximab in RA trial