What Is Rituximab Indicated For?
Rituximab is basically a chimeric monoclonal antibody that belongs to a subclass of the immunoglobulin G1 (IgG1). This monoclonal antibody drug can treat and significantly improve the prognosis as per current research in conditions ranging from pemphigus, non-Hodgkin’s lymphoma, and even autoimmune diseases like rheumatoid arthritis to life-threatening cancers.
What Are the Structure and Pharmacokinetics of Rituximab?
The monoclonal antibody structure is, in turn, comprised of two regions:
1. Murine Variable Region (Fab region):
This region has specific and varied sections defining a target antigen. The antibody attracts and secures an exclusive antigen causing or allowing the binding of Rituximab (IgG1) to the pre-B and mature B lymphocyte cells.
2. Constant human region (Fc region):
Rituximab is generally considered safe and tolerable in most patients with only mild, infusion-related complications. Though infectious complications can also exist, with supervision, physician support, and guidance, clinical trials with this drug in many patients globally have shown long-term efficacy and tolerability. However, the dosing in dermatological conditions may vary depending on the physician’s perspective of the treatment strategy.
Rituximab secondarily also acts upon immune cells like autoreactive T-effector cells, regulatory T cells, monocyte-derived macrophages, etc. The bioavailability of this drug is 100 % with intravenous infusion and an approximate elimination half-life that varies from 30 to 400 hours depending on the dosing regimen and duration of the advocated treatment plan.
What Is the Mechanism of Action of Rituximab?
Most autoimmune diseases associated with skin eruptions and blisters (the significant being pemphigus disease) are nearly always related to the production of autoantibodies against specific components found in the epidermis or the dermo-epidermal junction of the skin. About 20 CD4+ T-cells are pivotal for the autoantibody response against the desmosomal molecular adhesiveness in pemphigus vulgaris cases wherein desmoglein 3 (Dsg3) and Dsg1 are affected.
According to clinical research, the count or frequency of autoreactive CD4+ T cells, along with the determination of the peripheral serum autoantibody titers quantification, showed the following results in patients with good long-term prognosis in their general systemic health, i.e., Rituximab drug can induce peripheral B-cell depletion for the first 6 to 12 months. This can potentially lead to a decline of serum autoantibodies with clinical improvement outcomes in most pemphigus vulgaris patients.
Furthermore, the quantities of Dsg3-specific CD4+ T cells also have been identified to decrease among the serum antibodies. Hence its primary mechanism of action or effect lies in the depletion of autoreactive B cells and the specific downregulation of Dsg3-specific CD4+ T cells.
What Are the Clinical Trials and Efficacy of Rituximab?
Rituximab’s role has been fundamental in clinical trials and research, especially in T-cell-mediated autoimmune diseases. The most common condition in T cell-mediated disease is rheumatoid arthritis which has excellent scope in dosing regimen. It has also been used recently for conditions not directly linked to autoantibody production in patients suffering from atopic dermatitis.
It has been attributed that Rituximab can be used in the treatment of scleroderma, idiopathic thrombocytopenic purpura, angioedema, vitiligo, cutaneous lupus erythematosus, Castleman’s disease, and Schnitzler syndrome, etc.
Rituximab can potentially cause a decline in the B-cell production of one of the defined or unidentified autoantibodies, similar to its role in treating pemphigus diseases. Also, in conditions like SLE (systemic lupus erythematosus), Rituximab acts through the disruption or disturbance within the B and T-cell interactions. This leads to autoreactivity within the T-cell populations causing SLE.
What Is the Dosing Regimen of Rituximab?
In NHL, the prescribed dosing of Rituximab is usually an intravenous infusion of 375mg/m2 once weekly for four to eight consecutive weeks. It forms a dosing regimen either as a single agent or in combination with other chemotherapy agents. In RA, the dosing is two intravenous infusions of 1000 mg, usually given with an approximate gap of two weeks or 15 days from the previous dose.
Many physicians also advocate the administration of Methotrexate and Rituximab. Similarly, in autoimmune dermatologic disease or disorders, the commonly prescribed dosing range is around 375mg/m2 administered as an intravenous infusion weekly for four consecutive weeks. Regimens using Rituximab alongside other active medications such as immunosuppressants or immuno-modulator drugs have shown to be clinically effective for determining the long-term success rates of this drug usage in these patients.
Also, in some instances, even high-dose intravenous immunoglobulin (IVIG) can be beneficial in the treatment of varied autoimmune diseases. Most research studies on this drug now focus open the efficacy and the potential for reduction of autoantibodies in pemphigus Vulgaris severe patients ( treated with the combination of Rituximab (375mg/m2) and IVIG (2g/kg).
What Are the Adverse Effects of Rituximab?
The occurrence or incidence of any adverse events with Rituximab is usually low or generally uncommon in patients with no history of systemic or underlying undetected diseases. Apart from a few manifestations resulting from IV infusion, they can be well tolerated.
Some patients report symptoms of possible fever, chills, headache, weakness, nausea, itching, or skin rash. The physician or dermatologist can then advise temporary stoppage or reduction in the intravenous infusion till the patient’s symptoms are relieved or reversed. In addition, the physician can give prior medication to halt such adverse events ( in cases with immunosuppressive or severe systemic disease ) with analgesics, antihistamines, or glucocorticoids. In case of reactions, these patients should report immediately to their health care provider or physician for an emergency.
The listed conditions that Rituximab can potentially trigger an adverse reaction are:
Hepatitis B infections.
Hypersensitivity reactions of anaphylaxis.
History of patients with pulmonary events.
Patients with renal failure.
Hematological disorders like hemolytic anemias, cytopenias, and progressive multifocal leuko-encephalopathy infection.
Though the possibility is low except for limited infusion effects that eventually wear out, these severe adverse effects can be triggered due to immunosuppression, poor systemic health, or underlying, undetected malignancies. Only then the probability of a patient experiencing an adverse event occurs.
Although the FDA has approved Rituximab for treating non-Hodgkins lymphoma and rheumatoid arthritis, this drug has demonstrated significant clinical and therapeutic efficacy. Hence, it is an excellent futuristic drug in various other autoimmune and immune-mediated dermatological conditions for which even traditional therapy has failed or caused significant intolerance or side effects.
Frequently Asked Questions