Rituximab-Induced Hypogammaglobulinemia in Multiple Sclerosis

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis; Hypogammaglobulinemia
• Intervention / Treatment: Diagnostic test: Serum immunoglobulin titer

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.

• Study Type: Observational
• Enrollment (Anticipated): 170

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Sari, Iran, Islamic Republic of
    • Recruiting
    • Bu Ali Sina Hospital
    • Contact: athena sharifi razavi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Any adult patients with diagnosis of multiple sclerosis compatible with 2017 McDonald criteria and meet the inclusion and exclusion criteria from January 2020 until sample size will be reach, that refer to MS clinic of Bu Ali Sina Hospital, Sari,Iran.

Description

Inclusion Criteria:

1. diagnosis of multiple sclerosis compatible with 2017 McDonald criteria
2. history of treatment with ritximab at least for 18 month
3. written informed consent

Exclusion Criteria:

1. history of IVIG intake in 3 past month
2. history of plasmapheresis in 3 past month
3. unknown vaccination history
4. any indication for concurrent use of immunomodulator or immunosuppressor drug

Study Plan

How is the study designed?

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

Collaborators and Investigators

• Sponsor: Mazandaran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2020
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: February 22, 2020
• First Submitted That Met QC Criteria: February 22, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 10, 2020
• Last Update Submitted That Met QC Criteria: July 8, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Rituximab; Varicella Zoster; Hypogammaglobulinemia
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Hematologic Diseases; Blood Protein Disorders; Multiple Sclerosis; Sclerosis; Agammaglobulinemia; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: 6217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared with other researchers if asked
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR