Anti IL6R Reduce Complement Serum Level in Rheumatoid Arthritis Patients: Facts and Implications

Rheumatoid Polyarthritis Clinical Trial

Official title:

Anti IL6R Reduce Complement Serum Level in Rheumatoid Arthritis Patients: Facts and Implications: Monocentric Study in Belgian Center

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04505982
• Other study ID #: CHUB-IL6
• Status: Recruiting
• Start date: July 14, 2020
• Est. completion date: December 2020

Study information

• Verified date: August 2020
• Source: Brugmann University Hospital
• Contact: Tracy Vandergraesen, MD
• Phone: 003224754508
• Email: Tracy.VANDERGRAESEN[@]chu-brugmann.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 response.The 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 investigator's 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient = 18 years old

• Regular follow-up at CHU Brugmann Hospital for confirmed rheumatoid arthritis and meeting the ACR 2010 criteria

• On tocilizumab / sarilumab or for which this treatment is about to be initiated, in intravenous or subcutaneous form

Exclusion Criteria:

• Patients with a known complement deficiency before their rheumatic pathology

• Patient with hepatic impairment

Related Conditions & MeSH terms

• Arthritis
• Rheumatoid Polyarthritis

Intervention

Other:
• Data extraction from medical files
Data extraction from medical files

Locations

Country	Name	City	State
Belgium	Brugmann University Hospital	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
BADOT, Valerie

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demographic data	Age, sex	5 minutes
Primary	Body Mass Index	Body Mass Index	5 minutes
Primary	Medical History (descriptive listing)	Medical History (descriptive listing)	5 minutes
Primary	Neoplasia	Active neoplasia, or neoplasia dated less than 5 years	5 minutes
Primary	Disease Activity Score Calculator for Rheumatoid Arthritis- DAS28VS	The DAS28 is a measure of disease activity in rheumatoid arthritis . DAS stands for 'disease activity score' and the number 28 refers to the 28 joints that are examined in this assessment. A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.	5 minutes
Primary	Disease Activity Score Calculator for Rheumatoid Arthritis- DAS28CRP	The DAS28 is a measure of disease activity in rheumatoid arthritis . DAS stands for 'disease activity score' and the number 28 refers to the 28 joints that are examined in this assessment. A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.	5 minutes
Primary	Health Assessment Questionnaire (HAQ)	The Health Assessment Questionnaire Disability Index (HAQ) is developed for the assessment of disability in patients with Rheumatoid Arthritis. It focuses on two dimensions of health status, physical disability (eight categories), and pain. The eight categories review a total of 20 specific functions and evaluate patient's difficulty with activities of daily living over the past week.	5 minutes
Primary	Concomitant medication (descriptive listing)	Concomitant medication (descriptive listing)	5 minutes
Primary	Adverse events linked to the medication (descriptive listing)	Adverse events linked to the medication (descriptive listing)	5 minutes
Primary	Hemogram: normal (yes/no)	A hemogram contains all of the pertinent information required for assessment of hematopoiesis as well as a visual assessment of plasma appearance and measurement of total solids (an estimate of total protein) in plasma.	5 minutes
Primary	Leukocyte count	Leukocyte count	5 minutes
Primary	Blood Ionogram: normal (yes/no)	The blood ionogram analyses the ionic composition of the blood	5 minutes
Primary	Renal function: normal (yes/no)	Renal function	5 minutes
Primary	Hepatic function: normal (yes/no)	Hepatic function	5 minutes
Primary	Parathyroid hormone count	Parathyroid hormone count	5 minutes
Primary	Vitamin D count	Vitamin D count	5 minutes
Primary	Lipid balance: normal (yes/no)	Lipid balance allows monitoring of cholesterol (LDL-cholesterol and HDL-cholesterol) and triglycerides	5 minutes
Primary	Glucose concentration in the blood	Glucose concentration in the blood	5 minutes
Primary	Rheumatoid factor concentration	Rheumatoid factor is an autoantibody that induces inflammation and damage to the joints.	5 minutes
Primary	AntiCCP antibodies count	The detection of anti-CCP antibodies is used to help diagnose and prognosticate rheumatoid arthritis and differentiate it from other types of arthritis	5 minutes
Primary	FAN count	FAN are autoantibodies against elements of the nucleus	5 minutes
Primary	Sedimentation rate	Sedimentation rate	5 minutes
Primary	CRP count	CRP count	5 minutes
Primary	Complement fraction C1q count	Complement fraction C1q count	5 minutes
Primary	Complement fraction C3 count	Complement fraction C3 count	5 minutes
Primary	Complement fraction C3d count	Complement fraction C3d count	5 minutes
Primary	Complement fraction C3a count	Complement fraction C3a count	5 minutes
Primary	Complement fraction C4 count	Complement fraction C4 count	5 minutes
Primary	Complement fraction C4a count	Complement fraction C4a count	5 minutes
Primary	Complement fraction CH50 count	Complement fraction CH50 count	5 minutes
Primary	Complement fraction FB count	Complement fraction FB count	5 minutes
Primary	Lectin count	Lectin count	5 minutes
Primary	Lectin complement pathway serine protease 2 (MASP-2) count	Lectin complement pathway serine protease 2 (MASP-2) count	5 minutes
Primary	Mannose Binding lectin (MBL) count	Mannose Binding lectin (MBL) count	5 minutes
Primary	Complement SC5b9 count	Complement SC5b9 count	5 minutes
Primary	Fibrinogen count	Fibrinogen count	5 minutes
Primary	Lymphocyte B count: memory cells	Lymphocyte B count: memory cells	5 minutes
Primary	Lymphocyte B count: transitional cells	Lymphocyte B count: transitional cells	5 minutes
Primary	Lymphocyte B count: plasmablast cells	Lymphocyte B count: plasmablast cells	5 minutes