A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA®) to the reference product (Humira®) in patients with active rheumatoid arthritis

Abstract

BackgroundThis study aimed to compare efficacy and safety of test-adalimumab (CinnoRA®, CinnaGen, Iran) to the innovator product (Humira®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA).MethodsIn this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA® or Humira® every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety.ResultsPatients who were randomized to CinnoRA® or Humira® arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA® group was non-inferior to the Humira® group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA® and Humira® groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant.ConclusionCinnoRA® was shown to be non-inferior to Humira® in terms of efficacy at week 24 with a comparable safety profile to the reference product.Trial registrationIRCT.ir, IRCT2015030321315N1. Registered on 5 April 2015.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

“…In total, 21 studies evaluating bsDMARDs,52–72 18 studies evaluating boDMARDs73–90 and 21 studies evaluating tsDMARDs91–111 were included (online supplementary table S104). Overall, the incidence of major adverse events was low in all RCTs with mostly no differences between the active treatment and placebo or active comparator.…”

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis

“…All showed conclusive comparable results, irrespective of the compound (adalimumab (ADA), etanercept, infliximab and rituximab; for bsDMARD studied see table 1, online supplementary table S2.10 and online supplementary table S3.11). 30–55…”

Review of Biosimilar Trials and Data on Adalimumab in Rheumatoid Arthritis

“…In the following sections, we will review each in terms of clinical outcomes and trial characteristics. Other biosimilars will be mentioned in passing, including FKB327 by Fujifilm Kyowa Kirin Biologics which has phase III RA trial published in abstract form [ 33 , 34 ]; Sandoz’s GP2017 which has phase III plaque psoriasis trial in abstract form [ 35 ] and has been accepted for regulatory review [ 36 ]; and CinnoRA (Iran) and Exemptia (India) which have published RCTs on PubMed [ 37 , 38 ]. Additional pipeline biosimilars with completed/ongoing phase III trials are listed in Table 2 .…”