Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rheumatoid Arthritis—A Network Meta-Analysis of 36 Randomized Controlled Trials
by
Niels Graudal 1,*, Benjamin Skov Kaas-Hansen 2,3, Louise Guski 2, Thorbjørn Hubeck-Graudal 4, Nicky J. Welton 5
and Gesche Jürgens 2
Niels Graudal 1,*, Benjamin Skov Kaas-Hansen 2,3, Louise Guski 2, Thorbjørn Hubeck-Graudal 4, Nicky J. Welton 5 and Gesche Jürgens 2
1
The Lupus and Vasculitis Clinic VRR 4242, Copenhagen University Hospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark
2
Clinical Pharmacology Unit, Zealand University Hospital, Roskilde, Munkesøvej 18, 4000 Roskilde, Denmark
3
NNF Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
4
Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK 8200 Aarhus, Denmark
5
Deparment of Population Health Science, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Rd, Bristol BS8 2PS, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4350; https://doi.org/10.3390/ijms20184350
Received: 9 July 2019 / Revised: 24 August 2019 / Accepted: 29 August 2019 / Published: 5 September 2019
(This article belongs to the Special Issue Tumor Necrosis Factor (TNF) II)
The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars).
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Keywords:
rheumatoid arthritis; tumor necrosis factor (TNF) inhibitors; joint destruction; randomized controlled trial; network meta-analysis
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MDPI and ACS Style
Graudal, N.; Kaas-Hansen, B.S.; Guski, L.; Hubeck-Graudal, T.; Welton, N.J.; Jürgens, G. Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rheumatoid Arthritis—A Network Meta-Analysis of 36 Randomized Controlled Trials. Int. J. Mol. Sci. 2019, 20, 4350.
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