What is MabThera?
MabThera is a concentrate for the preparation of a solution for infusion (drip into a vein). It contains the active ingredient rituximab.
What is MabThera used for?
MabThera is a medicine used to treat blood cancers and inflammatory conditions described below:
- follicular lymphoma and diffuse large B-cell non-Hodgkin's lymphoma (two forms of non-Hodgkin's lymphoma, a blood tumor);
- chronic lymphocytic leukemia (CLL, another blood cancer that affects white blood cells);
- severe form of rheumatoid arthritis (an inflammatory condition of the joints);
- two inflammatory conditions of the blood vessels known as granulomatosis with polyangiitis (GPA or Wegener's granulomatosis) and microscopic polyangiitis (MPA).
Depending on the condition to be treated, MabThera can be given as monotherapy or in combination with chemotherapy, methotrexate or a corticosteroid. MabThera contains the active ingredient rituximab.
How is MabThera used?
MabThera is administered in a hospital setting. When used in combination with chemotherapy, MabThera is given on the first day of each chemotherapy cycle. Before
each infusion the patient must receive an antihistamine (to prevent allergic reactions) and a painkiller. It may also be necessary to administer a corticosteroid to reduce inflammation (particularly in patients with CLL with high levels of blood lymphocytes and in subjects with rheumatoid arthritis).
In the treatment of non-Hodgkin's lymphoma, the usual dose of MabThera is 375 mg per square meter of body surface area (calculated based on the patient's height and weight). The number and frequency of infusions depend on the type of lymphoma to be treated.
With regard to chronic lymphocytic leukemia, MabThera is given six times: the first dose of 375 mg / m2 is followed by the administration of five doses of 500 mg / m2. In order to avoid undesirable effects caused by the destruction of tumor lymphocytes, patients must be well hydrated and receive medicines that help stabilize uric acid levels before starting therapy.
For the treatment of rheumatoid arthritis, MabThera is given in two infusions of 1 000 mg two weeks apart, which can be repeated depending on the patient's response. Patients receiving MabThera for the treatment of rheumatoid arthritis must be given a special card that describes the symptoms of certain types of infections that can occur as undesirable effects of using MabThera, and invites interested parties to contact immediately a doctor if these symptoms appear. For all the details, see the summary of product characteristics included in the EPAR.
How does MabThera work?
The active substance in MabThera, rituximab, is a monoclonal antibody, which is an antibody (a type of protein) made to recognize a specific structure (antigen) present on some human cells and adhere to it. Rituximab was designed to recognize the CD20 antigen, which is present on the surface of all B lymphocytes. When rituximab adheres to the antigen, cell death is obtained, with consequent benefit for the treatment of lymphoma and CLL, since the cancerous B lymphocytes are destroyed. As for rheumatoid arthritis, the destruction of B lymphocytes occurs at the joints, with a consequent reduction in inflammation.
What studies have been carried out on MabThera?
MabThera has been studied in both forms of non-Hodgkin's lymphoma:
- for the treatment of follicular lymphoma, MabThera has been the subject of a main study conducted on 322 patients never previously treated for this disease. The study observed the efficacy obtained by adding MabThera to standard chemotherapy (CVP: cyclophosphamide, vincristine and prednisolone) by measuring the time elapsed before the disease reappeared. Three other studies, published in scientific publications, observed the effects deriving from the addition of MabThera to other types of chemotherapy on a total of 1 347 patients. Two studies also examined MabThera taken alone: one study looked at the overall response rate to MabThera in 203 patients already treated without success and the other maintenance study involved 334 patients and examined the time elapsed before a worsening of the disease;
- as regards diffuse large B-cell lymphoma, a study conducted on 399 patients, all over the age of 60, examined the efficacy of adding MabThera to CHOP chemotherapy. The main measure of effectiveness was the time that elapsed until the disease got worse or when treatment was needed to change).
In chronic lymphocytic leukemia the efficacy of adding adding MabThera to "FC" chemotherapy (fludarabine and cyclophosphamide) was studied in 817 patients who had never undergone treatment and in 552 subjects whose disease had reappeared after a previous treatment. The main measure of effectiveness was the time until the disease got worse. Further studies from the published scientific literature examined the effects of the combination of MabThera with other types of chemotherapy.
As for rheumatoid arthritis, MabThera has been studied in 520 patients in which the efficacy obtained by adding MabThera or a placebo (a dummy treatment) to methotrexate was compared. The study measured the number of patients who had a 20% improvement in the main symptoms of rheumatoid arthritis after 24 weeks.
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What benefit has MabThera shown during the studies?
In non-Hodgkin's lymphoma, patients treated with MabThera performed better than the untreated group:
- in the treatment of follicular lymphoma, subjects treated with MabThera in combination with CVP chemotherapy lived on average 25.9 months without the disease reappearing, compared to 6.7 months in patients treated with CVP therapy alone. The other three studies also showed that the addition of MabThera to other types of chemotherapy also improves patient outcomes. In studies of MabThera administered alone, 48% of unsuccessful patients at a previous treatment were shown to respond to MabThera. The study on the use of the medicinal product as maintenance showed that patients treated with MabThera lived on average 42.2 months without any signs of worsening of the disease, compared with 14.3 months for patients not treated with MabThera;
- in the treatment of diffuse large B-cell lymphoma, patients who underwent treatment with MabThera in combination with CHOP chemotherapy lived on average 35 months without signs of worsening the disease or without having to change therapy, compared with 13 months in subjects treated with the CHOP therapy.
Patients with CLL also performed better if treated with MabThera. Patients who had never been treated before lived on average 39.8 months without their disease getting worse if they were treated with MabThera in combination with CF, compared with 32.2 months for patients treated with FC chemotherapy only. With regard to patients whose disease had already reappeared after a previous treatment, the addition of MabThera allowed them to live 30.6 months without their disease getting worse, compared to 20.6 months for subjects in CF alone. Additional studies have also shown that the addition of MabThera to other types of chemotherapy also improves the therapeutic outcome of CLL patients.
In the treatment of rheumatoid arthritis MabThera was more effective than placebo: in 51% of patients treated with MabThera there was an improvement in symptoms, compared to 18% of patients treated with placebo.
What is the risk associated with MabThera?
In the treatment of non-Hodgkin's lymphoma or chronic lymphocytic leukemia, the most common side effects with MabThera (seen in more than one patient in ten) are bacterial infections, viral infections, bronchitis (inflammation of the respiratory tract in the lung), neutropenia (low levels of neutrophils, a type of white blood cells), leukopenia (decreased concentration of white blood cells in the blood), febrile neutropenia (neutropenia with fever), thrombocytopenia (lack of platelets), reactions associated with the infusion (mainly fever, chills and tremors), angioedema (swelling under the skin), nausea, itching, rash, alopecia (hair loss), fever, chills, asthenia (weakness), headache and reduced levels of IgG (a type of antibody). In the treatment of rheumatoid arthritis, the most common side effects (seen in more than one patient in ten) are infection, infusion-related reactions (for example, malaise, chills, rhinorrhea, urticaria and hot flushes), hypertension (increase blood pressure), rash, pyrexia (fever), itching, throat irritation and hypotension (decreased blood pressure). For the full list of all side effects reported with MabThera, see the Package Leaflet.
MabThera should not be used in patients who may be hypersensitive (allergic) to rituximab, mouse proteins or any of the other components. It should not be used in patients with a serious ongoing infection. In addition, patients with rheumatoid arthritis should not take MabThera if they have heart failure (an inability of the heart to pump enough blood around the body) or severe heart disease.
Why has MabThera been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of MabThera outweigh its risks for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis and therefore recommended that authorization be given to marketing for MabThera.
More information on MabThera:
On 2 June 1998, the European Commission granted a marketing authorization valid for MabThera, valid throughout the European Union, to Roche Registration Limited. The marketing authorization was renewed on 2 June 2003 and 2 June 2008.
For the full EPAR of MabThera, click here.
Last update of this summary: 08-2009. .
