Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed towards the CD20 antigen found on the surface of ordinary and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light and heavy-chain variable vicinity sequences and human consistent place sequences [A40017], [FDA label]. It became in the beginning permitted by the U.S. FDA in 1997 as a unmarried agent to deal with patients with B-cell Non-Hodgkin's Lymphoma (NHL) [L4811], but, has now been accepted for a spread of situations [FDA label]. On November 28, 2018, the united states FDA authorised _Truxima_, the primary biosimilar to Rituxan (Rituximab) [L4808].
Rituximab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lymphomas [A124]. The antibody leads to selective killing of B-cells. The following are the pharmacodynamic outcomes for various conditions, including non- Hodgkin's Lymphoma [FDA label]: **Non-Hodgkinâ€™s Lymphoma (NHL)** In Non-Hodgkin's Lymphoma patients, the administration of rituximab led to the depletion of circulating and tissue-based B cells. Among 166 patients in Study 1, circulating CD19-positive B cells were depleted within the first three weeks, showing sustained depletion for up to 6-9 months post-treatment in 83% of treated patients. B-cell recovery began at approximately 6 months and median B-cell levels returned to normal by 12 months following the completion of treatment [FDA label]. There were sustained and statistically significant decreases in serum IgM and IgG levels measured from 5-11 months following rituximab administration; 14% of patients showed IgM and/or IgG serum levels below the normal range [FDA label]. **Rheumatoid Arthritis** In rheumatoid arthritis (RA) patients, treatment with rituximab induced the depletion of peripheral B lymphocytes, with the majority of patients showing near complete depletion (CD19 counts below the lower limit of quantification, 20 c-lls/Î¼l) within 2 weeks after the first dose of rituximab. The majority of treated patients showed peripheral B-cell depletion, sustained for a minimum of 6 months. A small percentage of patients (~4%) had peripheral B-cell depletion that was sustained for more than 3 years after one course of treatment. Total serum immunoglobulin levels, IgM, IgG, and IgA were decreased at 6 months with the greatest change observed in IgM. At Week 24 of the first cycle of rituximab treatment, small percentages of patients experienced decreases in IgM (10%), IgG (2.8%), and IgA (0.8%) levels below the lower limit of normal (LLN). When rituximab was administered to RA patients during repeated rituximab treatment, 23.3%, 5.5%, and 0.5% of patients experienced decreases in IgM, IgG, and IgA concentrations below LLN at any time after receiving rituximab, respectively. The clinical consequences of decreases in immunoglobulin levels in RA patients treated with rituximab are not clear at this time. Treatment with rituximab in patients with RA was associated with a decreased level of several biologic markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid protein (SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti-citrullinated peptide (anti-CCP), and RF [FDA label] and was found to decrease disease symptoms [A125]. **Granulomatosis with Polyangiitis (GPA) (Wegenerâ€™s Granulomatosis) and Microscopic Polyangiitis** In GPA and MPA patients, peripheral blood CD19 B-cells were depleted to less than 10 cells/Î¼l after the first two infusions of rituximab, and remained at the same level in most (84%) patients through Month 6 of the treatment. By Month 12, most patients (81%) demonstrated signs of B-cell return with counts >10 cells/Î¼L. By Month 18, the majority of patients (87%) had counts >10 cells/Î¼L [FDA label].
Rituximab is indicated in the following conditions [FDA label]: **Nonâ€“Hodgkinâ€™s Lymphoma (NHL)** **Chronic Lymphocytic Leukemia (CLL)** **Rheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately-to severely-active RA** **Granulomatosis with Polyangiitis (GPA) (Wegenerâ€™s Granulomatosis) and Microscopic Polyangiitis (MPA)** **Moderate to severe Pemphigus Vulgaris (PV) in adult patients** The biosimilar (approved in November 2018), _Truxima_, is indicated For the treatment of adult patients with CD20-positive, B-cell non-Hodgkinâ€™s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy [L4808].
Rituximab is a monoclonal antibody that targets the CD20 antigen, which is expressed on the surface of pre-B and mature B-lymphocytes [A124], [A125], [A126], [FDA label]. After binding to CD20, rituximab mediates B-cell lysis (or breakdown). The possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) [FDA label]. Rituximab belongs to the immunoglobulin G1 (IgG1) sub-class, consisting of a murine variable region (Fab region) and a human constant region (Fc region). The Fab region has variable sections that define a specific target antigen, allowing the antibody to attract and secure its exclusive antigen, specifically the binding of rituximab (IgG1) to CD20 on pre-B and mature B lymphocytes. The Fc region is the tail end of the antibody that communicates with cell surface receptors to activate the immune system, in this case, a sequence of events leading to the depletion of circulating B lymphocytes by complement-dependent cell lysis, antibody-dependent cellular cytotoxicity, as well as apoptosis [A40017]. In regards to the mechanism of action in rheumatoid arthritis, B cells are thought to play a role in the pathogenesis of rheumatoid arthritis (RA) and the associated condition of chronic synovitis. B cells may act at various sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or the production of proinflammatory cytokines [FDA label]. The administration of rituximab in this condition has been shown to result in significant clinical and symptomatic improvements [A125], [FDA label].