Vitamin B12: a Biological Marker of Systemic Disease or Infection Flare-up in Patients Treated with Tocilizumab?

Tocilizumab is a monoclonal antibody that acts as an IL-6 receptor antagonist It is responsible for a reduction in the hepatic synthesis of inflammatory proteins, including CRP (C-reactive protein).

Thus, the diagnosis of a relapse of the autoimmune or auto inflammatory disease (AI/ID) or an infection is made difficult in patients treated with tocilizumab and there is to date no marker of inflammation validated in patients receiving tocilizumab.

Vitamin B12 is an essential element that participates to haematopoiesis, myelin integrity, neuronal function and DNA synthesis. Vitamin B12 is carried by haptocorrin and transcobalamin II (TCII). Vitamin B12 increases in many pathological situations, including infections and AI/ID due to the increase of its transport proteins elevation (mostly transcobalamin II).

The sponsor did not find any study in the literature studying the level of vitamin B12 or TCII in patients taking tocilizumab. The sponsor also did not find any physiopathological argument in favor of an inhibition of TCII synthesis by tocilizumab.

As such, TCII dosage could be of interest, but the dosage is not available in routine whereas vitamin B12 dosage is available in every laboratory and is four times cheaper.

The main objective is to study the variation in serum vitamin B12 level in case of clinical suspicion of AID/I flare or infection in patients treated with tocilizumab compared to the B12 level of the patient in remission period. , and excluding infection, under tocilizumab

Also, serum vitamin B12 will be measured during a biological assessment carried out either in the event of a suspected outbreak of MAI/I or infection, or in the event of remission (during the follow-up assessment carried out systematically in a patient on tocilizumab).

This determination of serum vitamin B12 will be carried out during a blood test carried out at the request of the patient's doctor.

The study will involve taking an additional tube of venous blood but will not result in additional venipuncture.

There will be no specific visit related to the study.

Eligibility Criteria:
Inclusion Criteria:

* Age \> 18 years old
* Patient with:

  * A diagnosis of rheumatoid arthritis according to ACR EULAR 2010 classification criteria
  * Or a diagnosis of polymyalgia rheumatica according to ACR EULAR 2012 classification criteria
  * Or a diagnosis of giant cell arteritis (with or without polymyalgia rheumatica associated) according to 2022 revised classification criteria
  * Or a diagnosis of systemic sclerosis according to ACR EULAR 2013 classification criteria
  * Or a diagnosis of Takayasu vasculitis according to ACR 2022 classification criteria
  * Or a diagnosis of Still disease according to Yamaguchi or Fautrel classification criteria
  * Or a diagnosis of VEXAS with UBA1 somatic mutation
  * Or a diagnosis of unclassified autoimmune or auto-inflammatory disease treated by tocilizumab
* Receiving intravenous or subcutaneous tocilizumab (treatment can be introduce before inclusion or started at the inclusion)
* Capable of giving informed consent
* Covered by a social protection system

Exclusion Criteria:

* Patient treated by oral or subcutaneous vitamin B12
* Pregnant or breastfeeding women
* Patient under guardianship or curatorship, deprived or liberty, placed under judicial protection
* Rejection to participate