Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis
Petra Baji
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Marta Pentek
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Sandor Szanto
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Pal Geher
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Laszlo Gul acsi
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Orsolya Balogh
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Valentin Brodszky
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S. Szanto Division of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Sciences Center
, Nagyerdei krt 98, 4032 Debrecen,
Hungary
1
M. Pentek Department of Rheumatology, Flor Ferenc County Hospital
, Semmelweis ter 1, 2143 Kistarcsa,
Hungary
2
P. Baji (&) M. Pentek L. Gulacsi O. Balogh V. Brodszky Department of Health Economics, Corvinus University of Budapest
, Fo}vam ter 8, 1093 Budapest,
Hungary
3
P. Geher No. I. Department of Rheumatology, Budai Irgalmasrendi Hospital
, Frankel Leo ut 54, 1023 Budapest,
Hungary
Objectives To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). Methods Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. Results Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. Conclusions This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals. JEL Classification I10 I19
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So far adalimumab, etanercept, golimumab and infliximab
have been approved by the European Medicine Agency
(EMA) for the treatment of adults with severe, active
ankylosing spondylitis (AS) who have responded
inadequately to conventional therapy (see detailed description of
the disease in Pentek et al. [1] in this Supplement).
In September 2013, the first biosimilar therapy, namely
infliximab-biosimilar (CT-P13, trade names: Remsima and
Inflectra) was licensed in the EU for the treatment of AS. The
results of a Phase 1, multicenter, double-blind randomized
controlled trial (RCT) with infliximab-biosimilar (called the
PLANETAS study) were published in May, 2013 [2]. The
trial was designed to demonstrate pharmacokinetic
equivalence and efficacy and safety comparability of
infliximab-biosimilar (CT-P13) and the originator infliximab in
active AS patients. The RCT was conducted at 46 sites across
10 countries in Europe, Asia and Latin America between
November, 2010 and December, 2011. Altogether, 250
patients were enrolled in the study. Besides
pharmacokinetics, the proportions of patients achieving 20 and 40 %
improvement according to the assessment of
Spondyloarthritis International Society1 response criteria (ASAS20 and
ASAS40) at weeks 14 and 30 were the endpoints to assess
efficacy [3]. (See the definition of ASAS response criteria in
the Methods Section). No significant differences were found
in the efficacy and safety of the originator infliximab and
infliximab-biosimilar. According to the study results,
ASAS20 and ASAS40 responses at week 30 were 70.5 and
51.8 % for infliximab-biosimilar and 72.4 and 47.4 % for
originator infliximab, respectively. The authors concluded
that pharmacokinetic, efficacy and safety profiles of the
infliximab-biosimilar and the originator infliximab were
equivalent in patients with active AS [2].
According to our knowledge, no meta-analyses have
been published yet in AS, which compare the efficacy and
safety of the infliximab-biosimilar treatment to the other
biological drugs indicated in AS. Thus, the aim of this
study was to carry out a systematic literature review and
meta-analysis of published RCTs in order to compare the
efficacy and safety of infliximab-biosimilar to adalimumab,
etanercept, golimumab and infliximab in AS.2
Besides the PLANETAS trial, no other RCTs,
presenting head-to-head comparison of biologicals, have been
published yet in this diagnosis [4]. Due to the difference in
comparators across the trials (infliximab-biosimilar is
compared to infliximab in the PLANETAS study, while
other biologicals are compared to placebo), tradit (...truncated)