Journal of Crohn's and Colitis (2014) 8, 710
Available online at www.sciencedirect.com
ScienceDirect
LETTER TO THE EDITOR
Biosimilars in Crohn's disease
The patent for some biological medicines used in the
treatment of Crohn's disease are close to expire. Biosimilars
are biologicals sufficiently similar to a biopharmaceutical
already approved by a regulatory agency.1 Several companies are developing biosimilars to tumor necrosis factor and
the first biosimilar submitted to the European agency for the
treatment of rheumatoid arthritis was developed in Korea by
Celltrion and was approved by regulators. The review
concluded that the biosimilar named Infectra has demonstrated similar quality efficacy and safety to Remicade.
Their commendation was not only for its use in rheumatoid
arthritis but also for the extrapolation for indication in other
forms of inflammatory arthritis.2 Surprise as it may be
extrapolation was also extended to Crohn's disease (CD).
There is plenty of evidence for the role of TNF on the
chronicity of the mucosal inflammation in CD but the cytokine
network associated with the immunopathogensis of the disease
is different from what one observes in immunoarthritis. The
metrics of improvement are also quite distinct when one
considers the evaluation of tenderness and swelling of joints
and migrates to diarrhea fistulas and abdominal pain. No
patient with CD responds or maintains a response to anti-tumor
necrosis factor (TNF) agents in a frequency considerably higher
than what is observed in rheumatoid arthritis and alternative
treatments are necessary. Natalizumab, a monoclonal antibody
to alpha-4 integrin approved for CD, has demonstrated efficacy
in randomized clinical trials in bowel disease but no effect on
arthritis was observed. Immunogenicity of infliximab in patients
with CD appears to occur substantially more frequently than in
patients with inflammatory arthritis. New biologics are in
development for CD such as interferon gamma and GM-CSF
that have no therapy activity in inflammatory arthritis.3 While
abbreviated pathway of approval will impact the final price of a
biosimilar we feel that extrapolation to inflammatory bowel
disease without a comparative trial is a controversial decision
that may not have all the immunopathogenetic rational that
one would expect in taking care of such patients. In fact, the
recent position from ECCO emphasizes that clinical efficacy of a
biosimilar in inflammatory arthritis should not be extrapolated
for IBD where efficacy cannot be predicted by effectiveness for
other indications.4 In conclusion, while anti-TNFs offer a distinct
advantage in the treatment of CD since it is a target therapy
other immunoinflammatory mechanisms are also playing a role
such as other cytokines and integrins. We suspect that
gastroenterologists similar to what is known for rheumatologists
are still not well familiarized with the challenges and concerns
in the development of biosimilars.5 However, our opinion is that
comparable trials should be performed between the reference
biologic and the biosimilar in CD before they get marketing
authorization for use in clinical practice.
Disclosures
None.
References
1. Scheinberg MA, Kay J. The advent of biosimilar therapies in
rheumatology—“O brave new world”. Nat Rev Rheumatol
2012;8(7):430–6 [5].
2. Beck A, Reichert JM. Approval of the first biosimilar antibodies in
Europe: a major landmark for the biopharmaceutical industry.
MAbs 2013;5(5):621–3.
3. Mulder DJ, Noble AJ, Justinich CJ, Duffin JM. A tale of two
diseases: the history of inflammatory bowel disease. J Crohns
Colitis Oct 2, 2013.
4. Danese S, Gomollon F, Governing Board and Operational Board of
ECCO. ECCO position statement: the use of biosimilar medicines
in the treatment of inflammatory bowel disease (IBD). J Crohns
Colitis 2013;7(7):586–9.
5. Scheinberg MA, Azevedo VF. Biosimilars in rheumatology:
perspective and concerns. What should the rheumatologist
know? Rheumatology (Oxford) Jul 22, 2013.
Morton Scheinberg
Division of Clinical Research, Hospital da AACD, São Paulo, Brazil
Hospital Albert Einstein, São Paulo, Brazil
E-mail address: [email protected].
3 December 2013
1873-9946/$ - see front matter © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.crohns.2013.12.002