A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy

Ann Rheum Dis. 2017 Jan;76(1):58-64. doi: 10.1136/annrheumdis-2015-207764. Epub 2015 Aug 28.


Objectives: To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.

Methods: This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence.

Results: 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF.

Conclusions: SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF.

Trial registration number: NCT01936181.

Keywords: Anti-TNF; DMARDs (biologic); Disease Activity; Rheumatoid Arthritis.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies / blood
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Infliximab / adverse effects
  • Infliximab / immunology
  • Infliximab / pharmacokinetics*
  • Infliximab / therapeutic use*
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Severity of Illness Index
  • Therapeutic Equivalency
  • Treatment Outcome


  • Antibodies
  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Infliximab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT01936181