Rituximab-Induced Hypogammaglobulinemia in Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
B cells are considered major contributors to multiple sclerosis (MS) pathogenesis, a role that has taken on renewed importance with the advent of B-cell-depleting therapies. Rituximab is being increasingly utilized as an off-label treatment option across MS patients . In addition, there have been increasing reports of rituximab causing hypogammaglobulinaemia and antibody deficiency across a variety of conditions including MS and related neuroinflammatory disorders. Therefore, the purpose of this study is to evaluate the rate of hypogammaglobulinemia in rituximab-treated MS adult patients and to assess the correlation with vaccination response during the treatment.

Detailed Description
-----------------
This is a prospective study which will be conducted in an educational medical hospitals in Sari, Iran.Adult patients with diagnosis of multiple sclerosis compatible with 2017 McDonald criteria and history of treatment with rituximab at least 3 times( 18 month) , enrolled to this study.Demographic patients' characteristics, including age, sex, vital sign, past medical history, drug history, will be recorded. Disease duration prior to rituximab, total rituximab dose, prior immunomodulatory drugs, Adverse drug reactions, the time interval between the last rituximab infusion and need for intravenous immunoglobulin replacement therapy and infections are recorded. Moreover, we will assess IgG and IgM levels, VZV titer at before rituximab administration and 6, 12, 18, months following the initiation of next dose of rituximab.

Official Title
-----------------
Hypogammaglobulinemia and Immunization Responses to Measles in Rituximab-treated Multiple Sclerosis Patients

Conditions
-----------------
Multiple Sclerosis, Hypogammaglobulinemia

Intervention / Treatment
-----------------
* Diagnostic Test: Serum immunoglobulin titer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of multiple sclerosis compatible with 2017 McDonald criteria history of treatment with ritximab at least for 18 month written informed consent Exclusion Criteria: history of IVIG intake in 3 past month history of plasmapheresis in 3 past month unknown vaccination history any indication for concurrent use of immunomodulator or immunosuppressor drug

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Serum immunoglobulin titer|Serum IgG and IgM levels, VZV titer every 6 month at before rituximab administration 3 times|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of hypogammaglobinemia | serum IgG concentration lower than g/L, | every 6 month until 18 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severity of hypogammaglobinemia | serum IgG concentration: mild (at risk) 5- 6.9 g/L, moderate 3- 4.9 g/L and severe < 3 g/L | every 6 month until 18 month | 
| immunization response to VZV vaccination | change of VZV antibody titre | every 6 month until 18 month | 
| Rate of infection | number of all infection events | during 18 month of fallow up | 
| type of infection | infections in different organs | During 18 month of study | 
| severity of infection events | need for hospitalization, oral or intravenous antibiotic therapy | During 18 month of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rituximab, Varicella Zoster, Hypogammaglobulinemia