What is the risk of recurrent infection and diabetes with Rituximab (Mabthera) treatment for multiple sclerosis?

From the Guidelines

Mabthera (rituximab) used for multiple sclerosis may increase the risk of recurrent infections, particularly hepatitis B reactivation, but has no direct link to diabetes, as evidenced by studies such as 1 and 1. When considering the use of Mabthera for multiple sclerosis, it is essential to weigh the potential benefits against the risks of recurrent infections and other adverse effects.

• Patients taking rituximab have approximately 1.5-2 times higher risk of developing infections, particularly respiratory tract infections, urinary tract infections, and herpes virus reactivations, as reported in studies like 1.
• The increased risk of infections occurs because rituximab depletes B cells, which are important components of the immune system, as noted in 1 and 1.
• The risk is higher in patients with prior infection history, advanced age, or those taking other immunosuppressive medications, highlighting the need for careful patient selection and monitoring.
• To minimize infection risk, patients should receive appropriate vaccinations before starting treatment, practice good hygiene, avoid close contact with sick individuals, and promptly report any signs of infection to their healthcare provider, as suggested by the evidence from 1.
• Regular monitoring of immunoglobulin levels may be recommended, as low levels can further increase infection susceptibility, as indicated in 1. Regarding diabetes, there is no established causal relationship between rituximab and diabetes development, though regular monitoring of blood glucose levels is part of standard care for patients on immunomodulatory therapies, as implied by the lack of direct evidence linking rituximab to diabetes in studies like 1 and 1.
• The primary concern with rituximab use in multiple sclerosis is the risk of hepatitis B reactivation, as highlighted in 1, which can be mitigated with appropriate screening and antiviral prophylaxis.
• Overall, the use of Mabthera for multiple sclerosis requires careful consideration of the potential risks and benefits, as well as close monitoring for adverse effects, to optimize patient outcomes and minimize morbidity and mortality.

From the FDA Drug Label

The administration of intravenous glucocorticoids prior to RITUXAN infusions reduced the incidence and severity of such reactions, however, there was no clear benefit from the administration of oral glucocorticoids for the prevention of acute infusion-related reactions. In the pooled, placebo-controlled studies, 39% of patients in the RITUXAN group experienced an infection of any type compared to 34% of patients in the placebo group. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis The incidence of serious infections was 2% in the RITUXAN-treated patients and 1% in the placebo group. In the experience with RITUXAN in 2578 RA patients, the rate of serious infections was 4.31 per 100 patient years. The most common serious infections ( greater than or equal to 0. 5%) were pneumonia or lower respiratory tract infections, cellulitis and urinary tract infections. Fatal serious infections included pneumonia, sepsis and colitis.

Risk of Recurrent Infection: The use of RITUXAN may increase the risk of recurrent infections, including serious infections such as pneumonia, cellulitis, and urinary tract infections.

• The incidence of serious infections was 2% in RITUXAN-treated patients and 1% in the placebo group.
• The rate of serious infections was 4.31 per 100 patient years in RITUXAN-treated RA patients. Risk of Diabetes: There is no direct information in the provided drug labels regarding the risk of diabetes associated with RITUXAN treatment 2, 2.

From the Research

Mabthera (Rituximab) for Multiple Sclerosis: Risk of Recurrent Infection and Diabetes

• The risk of recurrent infections with Mabthera (rituximab) treatment for multiple sclerosis (MS) is a concern, as rituximab is a B-cell depleting therapy that can increase the risk of infections 3, 4, 5.
• A study published in 2016 found that infections were seen in three patients (two of them were hospitalized for urinary tract infection and urosepsis) out of 56 patients treated with rituximab for MS or neuromyelitis optica (NMO) 3.
• Another study published in 2021 found that rituximab may increase slightly common infections compared with interferon beta or glatiramer acetate, and compared with natalizumab 4.
• A 2023 study found that rituximab treatment was associated with an increased risk of outpatient infections and serious infections compared with interferon-beta/glatiramer acetate (IFN/GLAT) 5.
• Regarding diabetes, there is no direct evidence from the provided studies that suggests a significant risk of diabetes associated with Mabthera (rituximab) treatment for MS.

Safety Profile of Mabthera (Rituximab) for Multiple Sclerosis

• The safety profile of Mabthera (rituximab) for MS has been evaluated in several studies, which suggest that rituximab is generally well-tolerated, with acceptable safety risks 3, 6, 4, 7.
• Common adverse events associated with rituximab treatment for MS include infusion-related reactions and infections 3, 4.
• Serious adverse events, such as serious infections, are relatively rare, but can occur, especially in patients with advanced disability or previous hospitalizations for infections 5.