I've
been interested in olokizumab for about decade now. In 2016 I've
written: „UCB still hasn’t
given up and keeps a low fire burning. I doubt that olokizumab will
be approved as a drug against rheumatoid arthritis.” [1] And now,
at the EULAR Meeting there are two studies. These studies concern
rheumatology and not Covid-19.
Let's
stay for a moment at the Covid-19 issue and the possible use of
IL-6-inhibitors. In patients with dramatic infectious diseases,
especially septic shock, IL-6 levels might increase 1000-fold
creating cytokine storm or cytokine release syndrome. This is life
threatening.
C.
Zhang and colleagues published a paper [2] in which they discussed
blocking IL-6
signal transduction pathway with tocilizumab, which could become an
effective drug for patients with severe COVID-19.
D.
McGonagle and colleagues published on the role of cytokines in
Covid-19 induced pneumonia and macrophage activation syndrome-like
disease [3]. They “discuss
the potential impact of timing of anti-cytokine therapy on viral
clearance and the impact of such therapy on intra-pulmonary
macrophage activation and emergent pulmonary vascular disease.”
But
back to rheumatology and the EULAR Annual Meeting. We already have
tocilizumab (Actemra) and sarilumab (Kevzara), which were approved
both by EMA (2009 and 2017) and FDA (2010 and 2017). So where is the
niche for olokizumab? Maybe that's the reason why the development of
the drug has been so slow. But maybe Covid-19 will also speed things
up.
There
has been a study by E.
Nasonov and colleagues [4]: “OP0021 OLOKIZUMAB,
MONOCLONAL ANTIBODY AGAINST IL6, IN PATIENTS WITH
MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS INADEQUATELY
CONTROLLED BY METHOTREXATE: EFFICACY AND SAFETY
RESULTS OF PHASE III CREDO-1 STUDY”. If you are surprised by he
Russian names, don be as in July 2013 there had been an announcement
by UCB: “UCB out-licenses RA drug olokizumab to Russia's
R-Pharm”.Back to the study. “428 patients were randomized to OKZ
64mg q2w (n=143), OKZ 64mg q4w (n=142), and PBO (n=143).” The
authors found: “Treatment with OKZ over a 24-week period was
associated with significant improvements in the signs, symptoms and
physical function of RA, ...” There has be a numerically higher
rate of adverse events and one death due to septic shock. There were
no differences between the two dosages of olokizumab in efficacy or
safety outcomes.
The
second study is on patient related outcomes. [5] Conclusion
sny E. Nasonov and olleagues:
„1. Treatment with OKZ over a 24-week period was
associated with significant improvements in PRO in patients with
moderate to severe RA. 2. There were no discernible differences
between the two regimens of OKZ from patient’s
perspective.”
Do
we need another IL-6-Inhibitor? If we compare olokizumab to
tocilizumab and sarilumab on the qualitativ level, there would not be
need for it. If it comes to altered demand (quantitativ level), there
might be need for it. But let's wait for the coming studies in
rheumatology and how the world copes with Covid-19.
Links and References:
[2] Zhang C, Wu Z, Li
JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19:
interleukin-6 receptor antagonist tocilizumab may be the key to
reduce mortality. Int J Antimicrob Agents.
2020;55(5):105954. doi:10.1016/j.ijantimicag.2020.105954
[3] McGonagle D, Sharif
K, O'Regan A, Bridgewood C. The Role of Cytokines including
Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation
Syndrome-Like Disease. Autoimmun Rev.
2020;19(6):102537. doi:10.1016/j.autrev.2020.102537
[4]
E. Nasonov1, R. Stoilov2, T. Tyabut3, M. C.
Genovese4 on behalf of Saeed Fatenejad (United States of
America), Diana Krechikova, Elena Korneva,
Alexey
Maslyansky, Tatiana Plaksina, Marina Stanislav, Sergey Yakushin,
Elena Zonova (Russian Federation). OP0021
OLOKIZUMAB,
MONOCLONAL ANTIBODY AGAINST IL6, IN
PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS
INADEQUATELY CONTROLLED BY METHOTREXATE: EFFICACY AND SAFETY
RESULTS OF PHASE III CREDO-1 STUDY. DOI:
10.1136/annrheumdis-2020-eular.1688
[5]
E. Nasonov1, M. Ivanova2, M. Samsonov3, T. Tyabut4, M. C. Genovese5
on behalf of Saeed Fatenejad (United States of America), Diana
Krechikova, Sofia Kuzkina, Alexey Maslyansky, Tatiana Plaksina,
Marina Stanislav, Sergey Yakushin, Elena Zonova (Russian Federation).
THU0176 OLOKIZUMAB IMPROVES PATIENT REPORTED OUTCOMES IN PATIENTS
WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS INADEQUATELY
CONTROLLED BY METHOTREXATE: RESULTS FROM THE DOUBLE-BLIND, RANDOMIZED
CONTROLLED PHASE III STUDY (CREDO-1). DOI:
10.1136/annrheumdis-2020-eular.2102
.
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