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

Ahmadreza Jamshidi, Farhad Gharibdoost, Mahdi Vojdanian, Soosan G Soroosh, Mohsen Soroush, Arman Ahmadzadeh, Mohammad Ali Nazarinia, Mohammad Mousavi, Hadi Karimzadeh, Mohammad Reza Shakibi, Zahra Rezaieyazdi, Maryam Sahebari, Asghar Hajiabbasi, Ali Asghar Ebrahimi, Najmeh Mahjourian, Amin Mohammadinejad Rashti, Ahmadreza Jamshidi, Farhad Gharibdoost, Mahdi Vojdanian, Soosan G Soroosh, Mohsen Soroush, Arman Ahmadzadeh, Mohammad Ali Nazarinia, Mohammad Mousavi, Hadi Karimzadeh, Mohammad Reza Shakibi, Zahra Rezaieyazdi, Maryam Sahebari, Asghar Hajiabbasi, Ali Asghar Ebrahimi, Najmeh Mahjourian, Amin Mohammadinejad Rashti

Abstract

Background: This 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).

Methods: In 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.

Results: Patients 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.

Conclusion: CinnoRA® 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 registration: IRCT.ir, IRCT2015030321315N1 . Registered on 5 April 2015.

Keywords: Adalimumab; Biosimilar; CinnoRA®; Rheumatoid arthritis.

Conflict of interest statement

Consent for publication

Informed consent forms were obtained from all the patients before conducting the screening procedure. Prior to collecting the signed informed consent forms from the patients, all of the contents were explained thoroughly to the patients by the coordinating investigators and they signed the forms with full awareness about the clinical trial conditions. These forms were signed and dated by the coordinating investigators as well. As specific data that would identify the participants are included in the consent forms, we are unable to provide them; hence, this is not applicable.

Competing interests

The authors of the study declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Trial profile. ITT intention-to-treat, PP per-protocol
Fig. 2
Fig. 2
Evaluation of non-inferiority of test-adalimumab to reference adalimumab in terms of the proportion of patients who met good and moderate disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) European League Against Rheumatism (EULAR) response in the per-protocol (PP) population at 12 weeks, 95% CI for the difference −0.009 to 0.16 (a); the intention-to-treat (ITT) population at 12 weeks, 95% CI for the difference −0.02 to 0.17 (b); the PP population at 24 weeks, 95% CI for the difference −0.04 to 0.04 (c); and the ITT population at 24 weeks, 95% CI for the difference −0.09 to 0.09 (d)
Fig. 3
Fig. 3
The proportion of patients achieving American College of Rheumatology 20%, 50% or 70% response (ACR20, ACR50, or ACR70) following treatment with test or reference adalimumab at 12 and 24 weeks

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Source: PubMed

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