Belimumab is an IgG1 lambda monoclonal antibody approved for treatment in humans. It was approved in the EU in 2011 as a treatment for systemic lupus erythematosus. It is used to support conventional therapies when they do not result in significant improvement in disease state.
What is belimumab?
Belimumab is sold under the trade name Benlysta. The genetically engineered monoclonal antibody is used to treat systemic lupus erythematosus. Belimumab (belimumabum) is sold under the trade name Benlysta. The genetically engineered monoclonal antibody is used to treat systemic lupus erythematosus (SLE). Its IgG1 molecule acts on B lymphocytes and stops their auto-immunological response. In systemic lupus, vessels within the connective tissues and skin become blocked by leukocyte deposits (collagenosis). The exact cause of the disease, which affects an average of one in two thousand people, is as yet unknown. However, medical science assumes an autoimmune reaction. Lupus erythematosus is often accompanied by symptoms such as flu-like weakening of the body, muscle complaints, polyarthritis, butterfly erythema on the cheeks and nose, and papules with skin scales. In systemic lupus, internal organs are also affected: central nervous system, kidneys, pleura, and pericardium. Patients often develop anemia and have elevated antibody status (anti-DNA-AK, anti-Sm, ANA).
Pharmacologic effects
Belimumab blocks the growth of immune system B leukocytes, so it has an immunosuppressive effect. It blocks the activity of the BLyS or BAFF cytokine. This is a messenger substance of the immune system that is responsible for the growth of B cells (“B lymphocyte stimulator”). If too much BLyS is present in the body, various autoimmune reactions occur simultaneously. According to some clinical studies, the monoclonal antibody has a significant effect on the course of SLE. However, to date, efficacy studies have only been conducted in SLE patients with less severe disease courses who did not have severe lupus renal inflammation or nerve impairment. This could possibly lead physicians to turn to the older, proven rituximab, which also improves more severe lupus, instead of belimumab. The monoclonal antibody has been shown to be effective in patients who have had no or reduced response to conventional treatment with corticosteroids (more severe cases) and ASA (milder cases), as well as cyclosporine A, azathioprine and cytostatics (all in off-label use). Fatigue (severe fatigue), which is common in lupus erythematosus, can also be significantly improved with the administration of belimumab. Belimumab binds to the soluble B-lymphocyte stimulator protein BLyS, thereby deactivating it and preventing it from acting in an autoimmune manner. Monoclonal antibody therapy may also be appropriate for other autoimmune diseases in which elevated BLyS levels can be detected in the blood. The antibody protein is degraded by being metabolized by proteolytic enzymes to peptides and amino acids. How the transformation proceeds in detail is still unclear. With regard to therapy in children and adolescents, there are no reliable scientific data available to date. In animal studies, the administration of Belimumab did not cause any damage to the embryo or the fertility of the mother. The number of B-leukocytes returned to normal a few months after birth. It is not known whether belimumab can promote cancer.
Medical Application and Use
Belimumab is used in systemic lupus erythematosus (SLE) when the disease does not improve significantly despite administration of immunosuppressants. In the first month of treatment, a short-term infusion lasting approximately one hour is administered on day 0, day 14, and day 28. Beginning in the second month, SLE patients receive their intravenous administration once per month. Patients with obesity are given a dose of 10 mg/kg body weight and underweight individuals are given correspondingly less. The dose level does not affect the efficiency of the administered drug, however, higher doses usually lead to more severe side effects. The drug is commercially available as a powder and must first be prepared into an infusion solution concentrate of 80 mg/ml.The active ingredient has a medical half-life of about 19 days. The body metabolizes an average of 215 ml/day. No dose adjustment is necessary in patients with impaired renal function, as the body excretes the drug accordingly: individuals with proteinuria have an increased excretion of more than 2 g daily. With delayed creatinine excretion, the active substance is broken down more slowly. An antihistamine and/or antipyretic may be given prior to infusion. If patients with systemic lupus erythematosus do not improve after at least six months on Benlysta, treatment with the monoclonal antibody is usually discontinued.
Risks and side effects
Side effects that may occur during belimumab therapy include: Fever, leukocyte deficiency, diarrhea, nausea, vomiting, infection, progressive multifocal leukoencephalopathy (PML), sleep disturbances, migraine headache, skin rash, facial edema, fatigue, depression, and pain in the arms and legs. Belimumab should not be used in cases of antibody hypersensitivity, live vaccines, chronic and recurrent infections, severe lupus renalitis, severe central nervous system lupus, HIV infection, hypersensitivity reactions, malignancies, hepatitis B or C, IgA deficiency, hypogammaglobulinemia, and after major organ or stem cell transplantation. In order to be able to immediately initiate the appropriate medical measures in the event of any hypersensitivity reactions, treatments with the monoclonal antibody should only be performed in facilities where appropriate medical professionals are available. Use during pregnancy is recommended only if no alternative is available. The drug also passes into breast milk. Therefore, breastfeeding women are advised to stop breastfeeding as soon as possible. Belimumab should not be co-administered with cyclophosphamide and other immunosuppressive agents.
