B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use

Abstract

The development of B cell-targeted biologics represents a major advance in the treatment of autoimmune rheumatic diseases. As with other immunosuppressive agents, risk of infection is a key clinical concern. This review summarises safety data from 15 years of experience of rituximab in autoimmune diseases with a particular focus on opportunistic infection and class-specific complications and infection risk. Rarely, cases of progressive multifocal leucoencephalopathy in rituximab-treated patients (5/100 000) have accumulated over time although no proven causal association has yet been shown. With repeat cycles of therapy, hypogammaglobulinaemia has been observed in a larger proportion of patients and is associated with increased risk of serious infections. The infection profile of the newer B celltargeted agent, belimumab in patients with active systemic lupus erythematosus is also discussed. Data from registries are needed to extend insights further and also to evaluate for any impact with the difference in mode of action of belimumab and infection risk in this population.(153 words) 4

The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults

“…However lupus patients may be at increased risk of developing PML compared to other rheumatic diseases (312). The risk of rituximab causing PML in rheumatic diseases including rheumatoid arthritis and SLE has been estimated at 5/100,000 which is less than the risk observed with some other immunosuppressants in other diseases (313).…”

Predicting Severe Infection and Effects of Hypogammaglobulinemia During Therapy With Rituximab in Rheumatic and Musculoskeletal Diseases

“…Despite the failure of randomized controlled trials (RCTs) in meeting their primary end points in systemic lupus erythematosus (SLE) , primary Sjögren's syndrome (SS) and inflammatory myopathies , RTX is commonly used off‐label in these indications and other various rheumatic and musculoskeletal diseases (RMDs), often in cases that are refractory to other systemic therapies . However, the immunomodulatory properties of biologic disease‐modifying antirheumatic drugs (bDMARDs) in general, including RTX, have raised safety concerns, prompting careful evaluation in RCTs and intensive surveillance after marketing . Data from RCTs and long‐term extension (LTE) studies of RTX in various RMDs have shown no major safety signals .…”

Effect of rituximab on the progression of rheumatoid arthritis–related interstitial lung disease: 10 years’ experience at a single centre

“…RA-ILD is the second most common cause of mortality in RA [2]. The high mortality has been attributed to uncontrolled systemic inflammatory disease, infections and complication from therapies [3,4]. While the treatment of RA has greatly improved in recent years with the introduction of biologic therapies, the use of such agents has often been restricted in RA-ILD due to concerns over safety.…”