Two New RA Switching Studies Show Biosimilars Safe, Efficacious

Two new reports of clinical switching studies in which patients undergoing treatment for rheumatoid arthritis (RA) were switched to a biosimilar version of the respective drugs provide some reassurance about the safety and efficacy of biosimilar products for infliximab (Remicade).

Switching studies, in which the patient is switched from the reference biologic to the biosimilar, have drawn the attention of physicians and the biopharmaceutical industry since the FDA made such studies a requirement for the agency’s potential approval of a biosimilar as interchangeable with the innovator drug.

The first study, conducted among 27 patients in the Netherlands and published in Clinical Rheumatology, evaluated 7 different rheumatic diseases. The patients had received infliximab for a median of 143 months. The researchers used therapeutic drug monitoring (TDM) as a tool to monitor the switch from Remicade to the biosimilar, Inflectra (developed by Pfizer) in RA patients in daily clinical practice over a 12-month period. Patients were monitored via blood draws just before the first infusion of the biosimilar and after the second, fourth, and seventh infusion thereafter.

The researchers measured infliximab trough levels, antibodies to infliximab (ATI), C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and validated disease activity scores (DAS). Their analysis found wide variation in the levels of infliximab, with only 56% within the proposed therapeutic range (two patients had very low levels and 1 patient very high). After switching to the biosimilar, 7 patients (26%) discontinued therapy, partially due to “subjective reasons.” No difference in infliximab levels, CRP levels, and DAS was found between the 4 time points examined.

The researchers conclude that no pharmacokinetic or clinical differences were found between Remicade and Inflectra in their diverse rheumatic cohort. They also concluded that TDM is a helpful tool to monitor patients switching from Remicade to Inflectra.

In the second study, published in BioDrugs and conducted in Korea, researchers compared the efficacy and safety of CT-P10 (Celltrion’s investigational rituximab biosimilar) in patients with RA who received CT-P10 from the outset (start of the randomized clinical trial [RCT] and also in the open-label extension [OLE] study, which was the maintenance group) with those who received infliximab during the RCT and switched to CT-P10 during the OLE (switch group). A total of 87 patients were enrolled; 58 and 29 had previously received CT-P10 or infliximab, respectively, in the RCT. Of these, 38 and 20 were treated with CT-P10 in the OLE, and thus comprised the maintenance and switch groups, respectively.

Efficacy (assessed by DAS28 and European League Against Rheumatism [EULAR]), safety, and immunogenicity were assessed. The mean change in the ESR from baseline at week 24 of the first OLE treatment in the maintenance and switch groups was -2.7 and -2.4, respectively, the researchers reported. ATIs were detected in 13.2% and 15% of patients in the maintenance and switch groups, respectively, at week 24 of the first OLE course. CT-P10 treatment was well tolerated when administered for up to 2 years after switching from infliximab. The proportion of patients with good-to-moderate EULAR responses was also comparable between groups, the investigators report.

The researchers concluded that similar disease activity responses were observed between patients with RA who continued treatment with CT-P10 and those who switched from innovator rituximab to CT-P10. In addition, switching from innovator rituximab to CT-P10 was not associated with any safety issues, and long-term treatment with CT-P10 was efficacious and well tolerated.

Called MabThera in Europe, CT-P10 is estimated to result in annual savings of €90 million.