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

NCT04505982 | Unknown

• 1 other identifier: CHUB-IL6
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Polyarthritis

Outcome Measures

Primary Outcomes (39)

• Demographic data

  Age, sex

  5 minutes

• Body Mass Index

  Body Mass Index

  5 minutes

• Medical History (descriptive listing)

  Medical History (descriptive listing)

  5 minutes

• Neoplasia

  Active neoplasia, or neoplasia dated less than 5 years

  5 minutes

• 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

• 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

• 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

• Concomitant medication (descriptive listing)

  Concomitant medication (descriptive listing)

  5 minutes

• Adverse events linked to the medication (descriptive listing)

  Adverse events linked to the medication (descriptive listing)

  5 minutes

• 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

• Leukocyte count

  Leukocyte count

  5 minutes

• Blood Ionogram: normal (yes/no)

  The blood ionogram analyses the ionic composition of the blood

  5 minutes

• Renal function: normal (yes/no)

  Renal function

  5 minutes

• Hepatic function: normal (yes/no)

  Hepatic function

  5 minutes

• Parathyroid hormone count

  Parathyroid hormone count

  5 minutes

• Vitamin D count

  Vitamin D count

  5 minutes

• Lipid balance: normal (yes/no)

  Lipid balance allows monitoring of cholesterol (LDL-cholesterol and HDL-cholesterol) and triglycerides

  5 minutes

• Glucose concentration in the blood

  Glucose concentration in the blood

  5 minutes

• Rheumatoid factor concentration

  Rheumatoid factor is an autoantibody that induces inflammation and damage to the joints.

  5 minutes

• 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

• FAN count

  FAN are autoantibodies against elements of the nucleus

  5 minutes

• Sedimentation rate

  Sedimentation rate

  5 minutes

• CRP count

  CRP count

  5 minutes

• Complement fraction C1q count

  Complement fraction C1q count

  5 minutes

• Complement fraction C3 count

  Complement fraction C3 count

  5 minutes

• Complement fraction C3d count

  Complement fraction C3d count

  5 minutes

• Complement fraction C3a count

  Complement fraction C3a count

  5 minutes

• Complement fraction C4 count

  Complement fraction C4 count

  5 minutes

• Complement fraction C4a count

  Complement fraction C4a count

  5 minutes

• Complement fraction CH50 count

  Complement fraction CH50 count

  5 minutes

• Complement fraction FB count

  Complement fraction FB count

  5 minutes

• Lectin count

  Lectin count

  5 minutes

• Lectin complement pathway serine protease 2 (MASP-2) count

  Lectin complement pathway serine protease 2 (MASP-2) count

  5 minutes

• Mannose Binding lectin (MBL) count

  Mannose Binding lectin (MBL) count

  5 minutes

• Complement SC5b9 count

  Complement SC5b9 count

  5 minutes

• Fibrinogen count

  Fibrinogen count

  5 minutes

• Lymphocyte B count: memory cells

  Lymphocyte B count: memory cells

  5 minutes

• Lymphocyte B count: transitional cells

  Lymphocyte B count: transitional cells

  5 minutes

• Lymphocyte B count: plasmablast cells

  Lymphocyte B count: plasmablast cells

  5 minutes

Study Arms (3)

Tocilizumab intravenous

Patients followed in the CHU Brugmann Hospital for a rheumatoid polyarthritis and treated according to standard of care with tocilizumab, intravenous

Other: Data extraction from medical files

Tocilizumab subcutaneous

Patients followed in the CHU Brugmann Hospital for a rheumatoid polyarthritis and treated according to standard of care with tocilizumab, subcutaneous

Other: Data extraction from medical files

Sarilumab subcutaneous

Patients followed in the CHU Brugmann Hospital for a rheumatoid polyarthritis and treated according to standard of care with sarilumab, subcutaneous

Other: Data extraction from medical files

Interventions

Data extraction from medical files OTHER

Data extraction from medical files

Sarilumab subcutaneous; Tocilizumab intravenous; Tocilizumab subcutaneous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients followed in the CHU Brugmann Hospital for a rhumatoid polyarthiritis and treated according to standard of care with tocilizumab / sarilumab or for which this treatment is about to be initiated, in intravenous or subcutaneous form

You may qualify if:

• 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

You may not qualify if:

• Patients with a known complement deficiency before their rheumatic pathology
• Patient with hepatic impairment

Sponsors & Collaborators

• BADOT, Valerie: lead

Study Sites (1)

Brugmann University Hospital

Brussels, 1020, Belgium

RECRUITING

Study Officials

• Tracy Vandergraesen, MD

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tracy Vandergraesen, MD

CONTACT

003224754508; Tracy.VANDERGRAESEN@chu-brugmann.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of rhumatology department

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 10, 2020
• Study Start: July 14, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 10, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)