Ignite Creation Date:
2024-05-06 @ 3:02 PM
Last Modification Date:
2024-10-26 @ 1:42 PM
Study NCT ID:
NCT04505982
Status:
UNKNOWN
Last Update Posted:
2020-08-10
First Post:
2020-08-06
Brief Title:
Anti IL6R Reduce Complement Serum Level in Rheumatoid Arthritis Patients Facts and Implications
Sponsor:
BADOT Valerie
Organization:
Brugmann University Hospital
Study Overview
Official Title:
Anti IL6R Reduce Complement Serum Level in Rheumatoid Arthritis Patients Facts and Implications Monocentric Study in Belgian Center
Status:
UNKNOWN
Status Verified Date:
2020-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Interleukin 6 is identified as a cytokine with pro and anti-inflammatory effects depending on the context to which it is exposed exerting a role in the expansion and activation of T lymphocytes in the survival expansion and the maturation of B lymphocytes and plasmablasts as well as in the regulation of the acute phase response The IL-6 receptor complex is a dimer in which each monomer is composed of an 80 kD subunit IL-6R or CD126 expressed in hepatocytes leukocytes and in megakaryocytes which binds IL- 6 and a 130 kD subunit gp130 or CD130 which is expressed ubiquitously Its effects are mediated mainly by the way of tyrosine kinases of the Jaks family and transcription factors of the STATs family
The complement system is made up of a set of plasma proteins cascading through three activation pathways classical alternate and lectin pathway This system is considered part of innate immunity It is also part of the acute phase responseThe complement has several functions cell lysis by formation of the membrane attack complex opsonization and activation of phagocytosis of foreign particles elimination of circulating immune complexes and regulation of the adaptive immunity response and inflammation via anaphylatoxins
After reviewing the literature the link between IL6 and the complement system can be summarized as an induction of factor C3 and factor B but also probably CD55 DAF or Decay acceleration factor and CD59 MAC-IP or MAC-Inhibitory Protein by interleukin-6 The effects of IL-6 on the lectin pathway on the other hand seem contradictory inhibition or induction of the synthesis of MASP1 3 and 2 depending on the experimental model
It has become common knowledge that anti-IL6 receptor monoclonal antibodies used in the treatment of patients with rheumatoid arthritis and other inflammatory conditions reduce the serum levels of acute phase proteins and in particular the levels of CRP But what about other acute phase proteins and in particular the complement
A recent study showed that the serum levels of the complement components C3 and C4 were also reduced after the use of tocilizumab and this as early as 4 weeks after the first administration To the investigators knowledge this is the only study reporting a decrease in complement during treatment with anti-IL6R
This study would allow the evaluation of complement parameters in the population of patients under treatment with antiIL6R tocilizumab or sarilumab within the CHU Brugmann Hospital in order to
confirm or not this observation
look for a possible secondary clinical consequence
compare this decrease with the activity of the disease in order to see if it could be a marker of effectiveness
put this decrease in parallel with the side effects tolerance of the treatment in order to see if it could be a marker of toxicity safety
This study will also investigate the subpopulations of B lymphocytes memory B transitional B and plasmablasts in order to assess whether the evolution of one of these lines would be predictive of a therapeutic response
Secondly this study would eventually allow
to improve the understanding of the mechanisms of action of the treatment on inflammatory markers by evaluating the activity of the residual complement
to raise the need to find new parameters for monitoring inflammatory activity in these patients since CRP assays are not very helpful
The complement system is made up of a set of plasma proteins cascading through three activation pathways classical alternate and lectin pathway This system is considered part of innate immunity It is also part of the acute phase responseThe complement has several functions cell lysis by formation of the membrane attack complex opsonization and activation of phagocytosis of foreign particles elimination of circulating immune complexes and regulation of the adaptive immunity response and inflammation via anaphylatoxins
After reviewing the literature the link between IL6 and the complement system can be summarized as an induction of factor C3 and factor B but also probably CD55 DAF or Decay acceleration factor and CD59 MAC-IP or MAC-Inhibitory Protein by interleukin-6 The effects of IL-6 on the lectin pathway on the other hand seem contradictory inhibition or induction of the synthesis of MASP1 3 and 2 depending on the experimental model
It has become common knowledge that anti-IL6 receptor monoclonal antibodies used in the treatment of patients with rheumatoid arthritis and other inflammatory conditions reduce the serum levels of acute phase proteins and in particular the levels of CRP But what about other acute phase proteins and in particular the complement
A recent study showed that the serum levels of the complement components C3 and C4 were also reduced after the use of tocilizumab and this as early as 4 weeks after the first administration To the investigators knowledge this is the only study reporting a decrease in complement during treatment with anti-IL6R
This study would allow the evaluation of complement parameters in the population of patients under treatment with antiIL6R tocilizumab or sarilumab within the CHU Brugmann Hospital in order to
confirm or not this observation
look for a possible secondary clinical consequence
compare this decrease with the activity of the disease in order to see if it could be a marker of effectiveness
put this decrease in parallel with the side effects tolerance of the treatment in order to see if it could be a marker of toxicity safety
This study will also investigate the subpopulations of B lymphocytes memory B transitional B and plasmablasts in order to assess whether the evolution of one of these lines would be predictive of a therapeutic response
Secondly this study would eventually allow
to improve the understanding of the mechanisms of action of the treatment on inflammatory markers by evaluating the activity of the residual complement
to raise the need to find new parameters for monitoring inflammatory activity in these patients since CRP assays are not very helpful
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None