Anti IL6R Reduce Complement Serum Level in Rheumatoid Arthritis Patients: Facts and Implications: Monocentric Study in Belgian Center
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Complement fraction FB count
Study Overview
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 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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Complement fraction FB count
Time Frame: 5 minutes
Complement fraction FB count
Demographic data
Time Frame: 5 minutes
Age, sex
Disease Activity Score Calculator for Rheumatoid Arthritis- DAS28VS
Time Frame: 5 minutes
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.
Adverse events linked to the medication (descriptive listing)
Time Frame: 5 minutes
Adverse events linked to the medication (descriptive listing)
Hemogram: normal (yes/no)
Time Frame: 5 minutes
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.
Leukocyte count
Time Frame: 5 minutes
Leukocyte count
Renal function: normal (yes/no)
Time Frame: 5 minutes
Renal function
Hepatic function: normal (yes/no)
Time Frame: 5 minutes
Hepatic function
Rheumatoid factor concentration
Time Frame: 5 minutes
Rheumatoid factor is an autoantibody that induces inflammation and damage to the joints.
Complement fraction C4 count
Time Frame: 5 minutes
Complement fraction C4 count
Body Mass Index
Time Frame: 5 minutes
Body Mass Index
Neoplasia
Time Frame: 5 minutes
Active neoplasia, or neoplasia dated less than 5 years
Disease Activity Score Calculator for Rheumatoid Arthritis- DAS28CRP
Time Frame: 5 minutes
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.
Concomitant medication (descriptive listing)
Time Frame: 5 minutes
Concomitant medication (descriptive listing)
AntiCCP antibodies count
Time Frame: 5 minutes
The detection of anti-CCP antibodies is used to help diagnose and prognosticate rheumatoid arthritis and differentiate it from other types of arthritis
Complement fraction C1q count
Time Frame: 5 minutes
Complement fraction C1q count
Complement fraction C3d count
Time Frame: 5 minutes
Complement fraction C3d count
Health Assessment Questionnaire (HAQ)
Time Frame: 5 minutes
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.
Glucose concentration in the blood
Time Frame: 5 minutes
Glucose concentration in the blood
FAN count
Time Frame: 5 minutes
FAN are autoantibodies against elements of the nucleus
Sedimentation rate
Time Frame: 5 minutes
Sedimentation rate
CRP count
Time Frame: 5 minutes
CRP count
Complement fraction C3a count
Time Frame: 5 minutes
Complement fraction C3a count
Complement fraction C4a count
Time Frame: 5 minutes
Complement fraction C4a count
Vitamin D count
Time Frame: 5 minutes
Vitamin D count
Lipid balance: normal (yes/no)
Time Frame: 5 minutes
Lipid balance allows monitoring of cholesterol (LDL-cholesterol and HDL-cholesterol) and triglycerides
Mannose Binding lectin (MBL) count
Time Frame: 5 minutes
Mannose Binding lectin (MBL) count
Lymphocyte B count: transitional cells
Time Frame: 5 minutes
Lymphocyte B count: transitional cells
Medical History (descriptive listing)
Time Frame: 5 minutes
Medical History (descriptive listing)
Blood Ionogram: normal (yes/no)
Time Frame: 5 minutes
The blood ionogram analyses the ionic composition of the blood
Parathyroid hormone count
Time Frame: 5 minutes
Parathyroid hormone count
Complement fraction C3 count
Time Frame: 5 minutes
Complement fraction C3 count
Lectin complement pathway serine protease 2 (MASP-2) count
Time Frame: 5 minutes
Lectin complement pathway serine protease 2 (MASP-2) count
Complement fraction CH50 count
Time Frame: 5 minutes
Complement fraction CH50 count
Lymphocyte B count: memory cells
Time Frame: 5 minutes
Lymphocyte B count: memory cells
Lymphocyte B count: plasmablast cells
Time Frame: 5 minutes
Lymphocyte B count: plasmablast cells
Lectin count
Time Frame: 5 minutes
Lectin count
Complement SC5b9 count
Time Frame: 5 minutes
Complement SC5b9 count
Fibrinogen count
Time Frame: 5 minutes
Fibrinogen count
Secondary Outcomes
No secondary outcomes reported
Investigators
BADOT, Valerie
Head of rhumatology department
Brugmann University Hospital