Sirukumab is a human MAB [monoclonal
antibody] that binds to the cytokine IL-6, designed for the treatment of
rheumatoid arthritis. So sirukumab will be competing with tocilizumab. Several
studies have been presented at the 2012 EULAR meeting in Berlin. [1]
There has been one publication on sirukumab
at the ACR 2015 Annual Meeting in San Francisco. So now we have one study. You
know, how suspicious I am, and this makes me even more suspicious. [2]
I might have had my suspicions two years ago,
but there have been nine studies on sirukumab presented at the 2017 EULAR
Annual Meeting in Madrid. Let’s have a closer look at some of the phase 3
studies.
Y. Sun and colleagues presented results of a
phase 3 Study [3]: “IMPROVEMENT IN MEASURES OF DEPRESSED MOOD AND ANHEDONIA IN
TWO RANDOMIZED, PLACEBO-CONTROLLED PHASE III STUDIES OF SIRUKUMAB, A HUMAN
ANTI-INTERLEUKIN-6 ANTIBODY, IN PATIENTS WITH RHEUMATOID ARTHRITIS”. In results
the authors write: “
Meta-analysis of 4 anti-IL-6 studies (1 siltuximab,
3 Sirukumab) revealed that anti-IL-6 treatment helps alleviate depressive
symptoms even after adjusting for changes in disease activity (Standardized
Mean Difference =0.25, p=0.03).” Conclusions: “Peripheral anti-IL-6 cytokine
treatment is associated with improvement in depressive symptoms in RA patients,
possibly supporting a role for IL-6 dysfunction in depression.” We don’t need a
phase 3 rheumatoid arthritis study for this statement. Cytokines play roles in
mood, depression, anxiety, pain, and not only in inflammation. There’s a very
recommendable overview by Janice K. Kiecolt-Glasera [4]. Siltuximab hasn’t been
tested in RA patients, so it’s strange that at one point data from a siltuximab
study had been included.
But maybe, we should just take notice of
sirukumab being tested in mayor depression.
Y. Tanaka and colleagues presented [5]: “LONG-TERM
EFFICACY AND SAFETY OF SIRUKUMAB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS
DESPITE ANTI-TUMOR NECROSIS FACTOR THERAPY: RESULTS OF THE RANDOMIZED, PHASE 3
SIRROUND-T STUDY”. In conclusions the authors discussed: “…, Sirukumab SC 50mg
q4w and 100mg q2w were well tolerated and reduced signs and symptoms of RA and
improved PROs [Patient Related Outcomes] through 52 wks of treatment, also
among pts who switched from placebo to Sirukumab.” No data on ACR70 response
rates!
D. Aletaha and colleagues looked at safety
data of the phase 3 study SIRROUND [6] and concluded: “SIR [sirukumab] is well
tolerated in pts [patients] with moderately to severely active RA [rheumatoid
arthritis]. Overall, no dose relationship was observed between SIR 50mg q4w and
100mg q2w for types or frequencies of AEs [adverse events]”.
Sirukumab treatment resulted in improvements
over time in health-related quality of life (HRQoL) [7].
T. Takeuchi and colleagues presented data on
[8]: “SUMMARY OF NEUTROPENIA IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH
SIRUKUMAB IN THE SIRROUND PHASE 3 CLINICAL TRIALS”. Conclusions: “Across phase
3 studies, there was no dose effect of SIR on neutropenia, and the use of
DMARDs did not have an apparent effect on neutropenia. The majority of grade 4
neutropenia with SIR was not associated with infections.” Just like
tocilizumab!
GSK has already “announced the submission of
a Biologics License Application (BLA) to the United States Food and Drug
Administration (FDA) by Janssen Biotech, Inc., (JBI), seeking approval of a
subcutaneous formulation of sirukumab” September 2016 [9] and a regulatory
submission to the European Medicines Agency (EMA) had been done earlier that
month. So it shouldn’t be long until tocilizumab will have a competitor? But
why should we change to sirukumab?
PS. Just a thought – can psychiatrists handle
monitoring and therapy of complications by a cytokine inhibitor?
Links and
References:
[3] Annals of the Rheumatic Diseases, volume
76, supplement 2, year 2017, page 250 / Session: Rheumatoid arthritis -
comorbidity and clinical aspects , (Poster Presentations) / DOI:
10.1136/annrheumdis-2017-eular.3263
[4] J.K. Kiecolt-Glasera and colleagues: Close
Relationships, Inflammation, and Health. Neurosci Biobehav Rev. 2010 September
; 35(1): 33–38. doi: 10.1016/j.neubiorev.2009.09.003.
[5] Annals of the Rheumatic Diseases, volume
76, supplement 2, year 2017, page 563 / Session: Rheumatoid arthritis - other
biologic treatment , (Poster Presentations) / DOI:
10.1136/annrheumdis-2017-eular.6486
[6] Annals of the Rheumatic Diseases, volume
76, supplement 2, year 2017, page 845 / Session: Rheumatoid arthritis - other
biologic treatment , (Poster Presentations) / DOI:
10.1136/annrheumdis-2017-eular.5176
[7] Annals of the Rheumatic Diseases, volume
76, supplement 2, year 2017, page 839 / Session: Rheumatoid arthritis - other
biologic treatment , (Poster Presentations) / DOI:
10.1136/annrheumdis-2017-eular.3904
[8] . Annals of the Rheumatic
Diseases, volume 76, supplement 2, year 2017, page 581 / Session: Rheumatoid
arthritis - other biologic treatment , (Poster Presentations) / DOI:
10.1136/annrheumdis-2017-eular.6413
.
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