Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis

Abstract

Background: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept.Methods: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%. Results:In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, −1.2%; 95% confidence interval, −10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32.Conclusions: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.

Differential retention of adalimumab and etanercept biosimilars compared to originator treatments: Results of a retrospective French multicenter study

“…Indeed, bsDMARDs are considered biologically similar to boDMARDs, thereby implying that the safety profile should be equivalent. In the literature, studies comparing the safety of bsDMARDs to boDMARDs did not find any difference in terms of adverse events, whatever the molecule ( 64 – 68 ). Our hypothesis is that boDMARDs are more often prescribed in more frail patients, who are intrinsically more prone to adverse events, because of rheumatologists’ greater experience of these treatments.…”

Efficacy, safety and immunogenicity of etanercept biosimilars versus reference biologics in patients with rheumatoid arthritis: A meta-analysis

“…A total of 366 records were identified from the databases, of which 206 unique records were screened after removing duplicate records. Out of these, the team assessed 33 full manuscripts for eligibility; 7 records from six RCTs with 2432 patients were included in our meta-analysis ( Figure 1 ) ( Bae et al, 2016 ; O'Dell et al, 2016 ; Emery et al, 2017a ; Emery et al, 2017b ; Matsuno et al, 2018 ; Matucci-Cerinic et al, 2018 ; Strusberg et al, 2021 ).…”

Therapeutic Equivalence of Biosimilar and Reference Biologic Drugs in Rheumatoid Arthritis

“…Sixteen (64%) trials [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][69][70][71][72][73][74][75][76][77][78][79][80][81][83][84][85][88][89][90][91]93 reported the use of concomitant methotrexate in both treatment groups, while in 9 trials 47,[63][64][65][66][67][68]82,86,87,92,94 (36%), it was unclear. eTable 1 and eTable 2 in Supplement 1 provide additional information on the included trials.…”

“…eFigure 3 in Supplement 1 shows the risk of bias in 25 trials. Fourteen trials [47][48][49][50][51][52][53][54][55][56][61][62][63][64][65][69][70][71][72][73][74][79][80][81][82][88][89][90]93 (56%) had a low risk of bias for random sequence generation, 16 trials [48][49][50][51][52][53][54][55][56][57][59][60][61][62][63][64][65][66][67][68][69][70][71][72]…”