A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis

Int J Rheum Dis. 2016 Nov;19(11):1157-1168. doi: 10.1111/1756-185X.12711. Epub 2015 Jul 14.


Aim: In this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA).

Method: In this multicentre, prospective, randomized, double-blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed.

Results: After 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28-CRP score was -2.1 ± 1.09 and -2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study.

Conclusion: The results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

Keywords: Exemptia; Humira; Zydus; adalimumab; biosimilar; rheumatoid arthritis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / adverse effects
  • Adalimumab / therapeutic use*
  • Adult
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / supply & distribution
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood
  • Biosimilar Pharmaceuticals / administration & dosage
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / therapeutic use*
  • C-Reactive Protein / metabolism
  • Double-Blind Method
  • Female
  • Humans
  • India
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Prospective Studies
  • Remission Induction
  • Severity of Illness Index
  • Therapeutic Equivalency
  • Time Factors
  • Treatment Outcome


  • Antirheumatic Agents
  • Biomarkers
  • Biosimilar Pharmaceuticals
  • C-Reactive Protein
  • Adalimumab