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Published on: May 22, 2020
Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab
Marine Perriguey1, Adil Maarouf1, Jan-Patrick Stellmann1
1From the Aix Marseille University (M.P., A.M., A.R., C.B., S.D., P.D., J.P., B.A.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie; Aix Marseille University (J.-P.S.), APHM, Hôpital de la Timone, Département de Neuroradiologie; Aix Marseille University (A.M., J.-P.S., A.R., C.B., S.D., P.D., J.P., B.A.), CRMBM UMR 7339, CNRS, Marseille, France.
Background And Objectives:
To determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX).
Methods:
This prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months.
Results:
We included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0-36], median Expanded Disability Status Scale 5 [range 0-8], median follow-up 3.5 years [range 1-5.8], and median number of RTX infusions 5 [range 1-9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0-33.1) were free of any infection and 92.0% (95% CI 87.1-97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75-0.98, p = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05-1.75, p = 0.01).
Discussion:
In PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.
Insights
In patients with multiple sclerosis receiving rituximab, low immunoglobulin G (IgG) levels are common and increase infection risk. Monitoring IgG is crucial for managing infections in these patients.
Area of Science:
- Neuroimmunology
- Pharmacology
- Infectious Disease Epidemiology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Rituximab (RTX) is an effective B-cell depleting therapy used for relapsing-remitting MS.
- Understanding RTX-associated risks, such as hypogammaglobulinemia and infections, is critical for patient management.
Purpose of the Study:
- To investigate the incidence of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) treated with rituximab (RTX).
- To assess the relationship between immunoglobulin G (IgG) levels and infection risk in PwMS on RTX.
Main Methods:
- A prospective observational study was conducted on 188 PwMS receiving RTX between 2015 and 2020.
- Data on patient demographics, disease characteristics, RTX infusions, immunoglobulin levels, and infection events were collected.
- Statistical analyses, including multivariate Cox proportional hazards models, were used to determine risk factors for infection.
Main Results:
- Over a median follow-up of 3.5 years, 70.7% of patients experienced symptomatic infections, and 5.9% had severe infections.
- After RTX treatment, a significant proportion of patients developed reduced IgG levels (<7 g/L in 44%, <6 g/L in 23.4%).
- Reduced IgG levels were associated with an increased risk of infection (HR=0.86, p=0.03), and lower IgG levels (<6 g/L) were linked to older age.
Conclusions:
- Hypogammaglobulinemia is a frequent complication in PwMS treated with RTX.
- Reduced IgG levels are a significant risk factor for infections in this patient population.
- Close monitoring of IgG levels and proactive infection management are essential for PwMS receiving RTX.
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