The number and pattern of withdrawals were comparable among the three treatment groups. Open in a separate window Figure 1 Patient disposition of the study population. switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, security and immunogenicity were assessed up to week 78. Results Efficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%C69.4% with INF/INF and 65.6%C68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were unfavorable for antidrug antibodies (ADA) up to week 54, CB1 antagonist 2 newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively. Conclusions The efficacy, security and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2. Trial registration number NCT01936181; EudraCT number: 2012-005733-37. Keywords: anti-tnf, dmards (biologic), rheumatoid arthritis, tnf-alpha, treatment Introduction The introduction of biosimilars has significantly impacted medical practice and the pharmaceutical industry.1 2 While biologicals are effective, they are also expensive, thus creating inequity by limiting their accessibility to patients and countries that can afford them.3 4 Biosimilars have the potential to improve access to treatment by reducing the financial burden on healthcare systems.5 While from a physicians perspective, biosimilars may be considered akin to chemical generics, making identical copies of biologicals is not technically feasible, and biosimilars undergo a more comprehensive regulatory pathway. This includes preclinical quality analysis, pharmacokinetic and pharmacodynamic assessments and phase III clinical evaluation, which is usually conducted in a randomised, double-blind fashion in at least one of the originators indications.6 7 Clinical trials of biosimilars are usually parallel-arm equivalence studies, with the primary aim to test CB1 antagonist 2 that this biosimilar has equivalent efficacy and comparable security to the reference product.6C10 An important issue surrounding biosimilars that cannot be tested by this approach is whether patients can be switched from your originator without major concerns.1 Because the main objective of biosimilars is to reduce drug costs and make biologicals more affordable to a larger population,11 switching patients from the original biological to a biosimilar is a likely concern in clinical practice to capitalise on the cost reduction. However, as previously mentioned, biosimilars are not identical to their initial counterparts. Additionally, biologicals generally have issues with immunogenicity, which can be associated with decreased efficacy and, in some cases, with adverse events (AEs).12 Therefore, data regarding switching from originators to biosimilars are desirable to strengthen the demonstration of biosimilarity. SB2 (Samsung Bioepis, Incheon, Republic of Korea) and reference infliximab (INF; Remicade, Janssen CB1 antagonist 2 Biotech, Horsham, Pennsylvania, USA) have been shown to have equivalent efficacy and comparable structure, function, pharmacokinetic parameters, immunogenicity and safety.8 13 14 SB2 was approved in the USA on 21?April 2017 and has also been approved in Norway, Liechtenstein, Iceland?and Australia, in addition to having been approved in the Western Union15 and Korea.16 The clinical efficacy and safety results of SB2 for the treatment of rheumatoid arthritis (RA) were previously reported, up to 54 weeks, based on a phase III equivalence study conducted using the aforementioned parallel-arm design.8 17 The objectives of the present transition-extension period (described as transition period hereafter) of the phase III study were to investigate whether individuals on INF could be readily switched to SB2 without major issues and whether comparable efficacy, safety and immunogenicity were maintained Rabbit polyclonal to AGO2 after the switch when compared with both ongoing reference INF as well as SB2. Methods Methods for the initial randomised, double-blind period of this multinational, multicentre, parallel?group study (weeks 0C54) have been previously described.8 17 The study originally enrolled patients 18C75 years of age diagnosed with moderate to severe RA (1987 American College of Rheumatology (ACR) CB1 antagonist 2 criteria) despite methotrexate therapy. The methods below focus on the transition period (weeks 54C78). Patients Those who completed the week 54 visit of the randomised, double-blind period and were willing to participate were eligible for the transition period. Patients who experienced any significant medical condition(s) during the randomised, double-blind period, such as the occurrence of a serious AE (SAE) or intolerance of SB2 or INF, and who were determined to be unfit for further treatment were excluded. Study design Patients were in the beginning randomised (1:1) to receive either SB2 or INF at weeks 0, CB1 antagonist 2 2?and 6 and then every 8 weeks thereafter until week 46 (randomised, double-blind period). The protocol was amended during.