Monoclonal Antibodies

Monoclonal Antibodies + ++ Suitability Safety Efficacy Cost Monoclonal Antibodies + ++ Suitability: For a flight attendant like her, monoclonal antibody therapy is not suitable since it is given intravenously, and the biweekly or monthly medications are going to be difficult for her since she is constantly traveling. Safety: The most common safety issue is the risk for acquiring infections. Other noted general adverse reactions for the drug group are infusion-site reactions (since all are given intravenously), diarrhea, fever, nausea, and most commonly infections, both mild and severe. Efficacy: Monoclonal antibodies are directed against specific molecular targets, such as CD20 molecule of B cells, TNF-alpha, the various interleukins, and many others. The antibodies aim to decrease B cell count which can reduce the number of autoantibodies present in SLE. More concrete studies are needed for monoclonal antibodies to prove its efficacy on SLE. Studies are conflicting about the efficacy of the various monoclonal antibodies. Some (rituximab) are only used for severe and refractory cases, and some (belimumab) are not yet tested for severe cases of SLE. Cost: The drugs are expensive and not all types of monoclonal antibodies are available in the Philippines yet, especially the newer and possibly more effective ones. The cost of the drugs may be too much given her job and it outweighs any potential benefit the drugs may have on her.

Monoclonal Antibody Suitabilty Safety Efficacy Cost Rituximab + Belimumab ++ Tocilizumab Infliximab Rituximab Suitability: the drug is only given intravenously, either once a week or once every two weeks. It is contraindicated in severe infections. Safety: Most common adverse reaction is infection. other reactions include infusion reactions (erythema, pruritus at infusion site), headache, urticaria, nausea, hypo- and hypertension. A severe adverse reaction is progressive multifocal leukoencephalopathy (PML). Efficacy: It binds to the CD20 molecule on B lymphocytes and decreases their levels in the body. The drug is only used for severe and refractory SLE and is not advised as a first-line drug for SLE. Cost: The drug is very expensive, amounting to 89269 pesos per 50 ml vial of 10mg/ml. (Given that dosage is 375mg/m2 once a week or 1g/m2 every 2 weeks in a month) Belimumab Suitability: the drug is only given intravenously, at weeks 0, 2, and 4, then is given monthly at a dose of 10mg/kg. It is contraindicated in severe infections and it is contraindicated to give live vaccines during treatment. Safety: Adverse reactions include nausea, diarrhea, fever, infusion-site reactions, and most commonly, infections. Efficacy: This inhibits the B lymphocyte stimulator (BlyS) needed for maturation of B cells to plasma cells, which will eventually decrease the number of autoantibodies produced by B cells during SLE. Significant decrease in SLE flares, SLE activity, and disease worsening was observed, but another study notes the drug has been shown to be ineffective in people with African lineage. It has not yet been tested extensively in severe forms of SLE. Cost: The drug is expensive, and is not yet available in the country. (only approved by US FDA last March, 35,000 dollars a year) Tocilizumab Suitability: the drug is only given intravenously every 2 weeks at dose of 4 mg/kg. Again, it is contraindicated in severe infections and it is contraindicated to give live vaccines during treatment. Safety: Significant adverse reactions have been observed, such as herpes zoster infection, bacterial infections, and severe neutropenia. Other reactions include diarrhea, leukopenia, infusion-site reactions, and increased triglycerides. Efficacy: Tocilizumab is an anti-interleukin 6 receptor monoclonal antibody, which may have an effect on B cell maturation and differentiation as well as on inflammation. It can reduce swollen joints and decrease disease activity (SLE disease activity index), but further studies are needed to ascertain the mechanism of action and its clinical efficacy. Cost: It is expensive, a 200mg/10mL vial costs 19824 pesos. (If patient is 50kg, then this is given once every 2 weeks) Infliximab Suitability: the drug is only given intravenously every 2 weeks at dose of 3-5 mg/kg. Again, it is contraindicated in severe infections and it is contraindicated to give live vaccines during treatment. It is also contraindicated in patients with moderate to severe cardiac failure. Safety: Some adverse reactions include infusion-site reactions, headache, rash, nausea, and stomach upset. There is also an increased occurrence of severe and life-threatening infections such as sepsis, tuberculosis, or fungal infections in infliximab-treated patients. Efficacy: It is an anti-TNF alpha monoclonal antibody, but the role of TNF-alpha in SLE is still ambiguous. There is a noted decline in efficacy after long period of treatment. Cost: It is again expensive, 100mg/20ml vial costs 35000 pesos. (so assuming 50 kg patient, 3mg/kg dose, one and a half vial every 2 weeks.) Source: Ponticelli C and Moroni G. (2010). Monoclonal Antibodies for SLE. Pharmaceuticals. 3:300-322.

Rituximab IV form Binds to CD20 molecule on B lymphocytes, decreasing levels of B cells in the peripheral blood, lymph nodes, and bone marrow Belimumab Inhibits B-lymphocyte stimulator (BlyS) needed for maturation of B cells to plasma cells, decreasing number of plasma B cells and subsequently decresing number of autoantibodies produced during SLE Mabthera (vial) 10 mg/1 mL x 10 mL x 2's (P36422) Ocrelizumab Mabthera 10 mg/1 mL x 50 mL x 1's (P89269) Veltuzumab Mabthera 10 mg/1 mL x 2's (P178538) NA pa rin