The introduction of targeted biological therapies has improved the treatment of immune inflammatory arthritis and other autoimmune diseases, in particular, Crohn’s disease (CD). The monoclonal antibodies infliximab and adalimumab have shown beneficial effects in patients with CD and high disease activity. The forthcoming introduction of biosimilars is expected to improve access to these expensive medications with an expected reduction in price ranging from 20 to 40 per cent of the present cost.
The first biosimilar of Remicade (infliximab) was approved by the European regulatory agency with two names Remsima or Inflectra for all indications for which the originator infliximab is licensed, including CD. While comparability trials with Remsima or Inflectra were never made for CD the agency was comfortable in the support of such extrapolation [1].
The Korean biosimilar of infliximab (Remsima; Celltrion) was approved by the Canadian regulatory agency for inflammatory arthritis. However, in Canada, extrapolation* from autoimmune arthritis to CD and ulcerative colitis (UC) was not granted [2]. While the reasons behind the Canadian agency’s decision are not totally clear there are several arguments as to why extrapolation of indication should not be granted for its use in CD if adequate comparability trials were not performed. While the role of tumour necrosis factor (TNF) on the chronicity of mucosal inflammation in CD raises no doubts, the cytokine network associated with the pathogenesis of CD is substantially different from the one observed in immune inflammatory arthritis. There are now several biologicals that are helpful in the control of disease activity in CD which are not effective in immune arthritis and vice versa [3].
Biosimilars are becoming a reality in rheumatology and it is expected that this will also happen in gastroenterology. However, it is desirable that this occurs after the design of comparability trials demonstrating clinical equivalence safety and well-powered statistical approaches. During the 10th annual Congress of the European Crohn’s and Colitis Organisation (ECCO), the manufacturer of the Remsima biosimilar presented data on the expected savings that the use of the infliximab biosimilar in CD may generate in European countries, based on price discount scenarios and prevalence of CD.
However, no data is yet available on comparability trials that should make the gastroenterologist confident that Remsima is effective in controlling abdominal pain fistulas and diarrhoea in a similar manner to Remicade.
Korea-based Celltrion is now seeking FDA approval of its Remsima biosimilar in the same indications of the originator. But it remains to be seen how the American agency will handle the extrapolation to use in CD without comparability trials [4].
*Extrapolation involves extending and applying the data from clinical studies regarding one medical condition to another medical condition.
Conflict of interest
Conflict of interest statement not provided.
Abstracted by Dr Morton A Scheinberg, Hospital Israelita Albert Einstein and Hospital Abreu Sodré-AACD (a bone and joint hospital), Saõ Paulo, Brazil.
Editor’s comment
Physicians may not be well informed about the scientific concept underlying the principle of extrapolating indications for biosimilars.
The European Medicines Agency considers extrapolation of efficacy and safety data from one indication to another may be considered if biosimilarity to the reference product has been shown by a comprehensive comparability programme. If the relevant mechanism of action of the active substance and the target receptor(s) involved in the tested and in the extrapolated indication(s) are the same, extrapolation is usually possible [5].
EMA has also specifically listed the scientific rationale behind its decision to extrapolate the indications of biosimilar infliximab to include inflammatory bowel disease, i.e. CD and UC. This was based on the totality of evidence, which indicated similar efficacy and safety of the biosimilar and the reference product in all therapeutic indications of infliximab [5].
References
1. Scheinberg M. Biosimilars in Crohn’s disease. J Crohns Colitis. 2014;8(7):710.
2. GaBI Online - Generics and Biosimilars Initiative. Subsequent entry biologics approved in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Jun 12]. Available from: www.gabionline.net/Biosimilars/General/Subsequent-entry-biologics-approved-in-Canada
3. Scheinberg M, Castañeda-Hernández G. Anti-tumor necrosis factor patent expiration and the risks of biocopies in clinical practice. Arthritis Res Ther. 2014;16(6):501.
4. Scheinberg M. Therapy: facing up to biosimilar agents-the ACR position. Nat Rev Rheumatol. 2015;11(6):322-4. doi: 10.1038/nrrheum.2015.57.
5. GaBI Online - Generics and Biosimilars Initiative. Extrapolation of indications in biosimilars: infliximab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Jun 12]. Available from: www.gabionline.net/Biosimilars/Research/Extrapolation-of-indications-in-biosimilars-infliximab
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