Rituximab, sold under the brand name Rituxan among others, is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

medication used to treat certain

autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

and types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. It is used for

non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. ...

, chronic lymphocytic leukemia (in non-geriatric patients),

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is a form of vasculitis ...

, idiopathic thrombocytopenic purpura, pemphigus vulgaris,

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...

and

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

-positive mucocutaneous ulcers. It is given by slow injection into a vein.

Biosimilar A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved v ...

s of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza (F.K.A. Tuxella), Rixathon, Ruxience, and Truxima. Common side effects which often occur within two hours of the medication being given include rash, itchiness,

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, and shortness of breath. Infections are also common. Severe side effects include reactivation of

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

in those previously infected, progressive multifocal leukoencephalopathy,

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...

, and death. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

is safe for the developing fetus or newborn baby, but it is not proven harmful. Rituximab is a chimeric

against the protein

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase (CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene e ...

, which is primarily found on the surface of immune system

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

. When it binds to this protein it triggers cell death. Rituximab was approved for medical use in 1997. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. Rituximab is co-marketed by

Biogen Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. History ...

and

Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...

in the U.S., by

Hoffmann-La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

in Canada and the European Union,

Chugai Pharmaceuticals is a drug manufacturer operating in Japan. It is a subsidiary controlled by Hoffmann-La Roche, which owns 62% of the company as of 30 June 2014. The company is headquartered in Tokyo. Osamu Nagayama is the current representative director and ...

, Zenyaku Kogyo in Japan and

AryoGen AryoGen Pharmed ( fa, آریوژن فارمد) is an Iranian biopharmaceutical company specializing in manufacturing Therapeutic Monoclonal antibodies and some other recombinant proteins. History AryoGen is a biopharmaceutical company created o ...

in Iran.

Medical uses

Rituximab is a chimeric monoclonal antibody targeted against CD20 which is a surface antigen present on B cells. Therefore, it acts by depleting normal as well as pathogenic B cells while sparing plasma cells and hematopoietic stem cells as they do not express the CD20 surface antigen. In the United States, rituximab is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to treat: #

(NHL) # chronic lymphocytic leukemia (CLL) #

having inadequate response to one or more

TNF inhibitor A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ...

s # vasculitis such as

and

microscopic polyangiitis Microscopic polyangiitis is an ill-defined autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. Signs and symptoms C ...

# moderate to severe pemphigus vulgaris # in combination with chemotherapy for children (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).

Blood cancers

Rituximab is used to treat cancers of the white blood system such as

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

s and

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

s, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and nodular lymphocyte predominant Hodgkin's lymphoma. This also includes Waldenström's macroglobulinemia, a type of NHL. Rituximab in combination with

hyaluronidase Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid (HA). Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyal ...

human, sold under the brand names ''MabThera SC'' and ''Rituxan Hycela'', is used to treat

follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normal ...

diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibody, antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual Incidence (epidemiology), in ...

, and chronic lymphocytic leukemia. It is used in combination with

fludarabine Fludarabine is a purine analogue and antineoplastic agent. It is generally used as its 5-O-phosphorylated form known as fludarabine phosphate, sold under the brand name Fludara among others. It is a chemotherapy medication used in the treatmen ...

and

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

to treat previously untreated and previously treated CD20-positive chronic lymphocytic leukemia.

Autoimmune diseases

Rituximab has been shown to be an effective

treatment in three randomised controlled trials and is now licensed for use in refractory rheumatoid disease. In the United States, it has been FDA-approved for use in combination with

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

(MTX) for reducing signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more anti-

TNF-alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

therapy. In the European Union, the license is slightly more restrictive: it is licensed for use in combination with MTX in patients with severe active RA who have had an inadequate response to one or more anti-TNF therapy. There is some evidence for efficacy, but not necessarily

safety Safety is the state of being "safe", the condition of being protected from harm or other danger. Safety can also refer to risk management, the control of recognized hazards in order to achieve an acceptable level of risk. Meanings There are ...

, in a range of other autoimmune diseases, and rituximab is widely used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

to treat difficult cases of

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

chronic inflammatory demyelinating polyneuropathy Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called c ...

and autoimmune

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

s. The most dangerous, although among the most rare, side effect is progressive multifocal leukoencephalopathy (PML) infection, which is usually fatal; however only a very small number of cases have been recorded occurring in autoimmune diseases. Other autoimmune diseases that have been treated with rituximab include

autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...

pure red cell aplasia Pure red cell aplasia (PRCA) or erythroblastopenia refers to a type of aplastic anemia affecting the precursors to red blood cells but usually not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells. There are multiple ...

thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, h ...

(TTP), idiopathic thrombocytopenic purpura (ITP),

Evans syndrome Evans syndrome is an autoimmune disease in which an individual's immune system attacks their own red blood cells and platelets, the syndrome can include immune neutropenia. These immune cytopenias may occur simultaneously or sequentially. Its o ...

, vasculitis (e.g.,

), bullous skin disorders (for example

pemphigus Pemphigus ( or ) is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root ''pemphix'', meaning "pustule". In pemphigus, autoantibodies form against desmoglein, whi ...

pemphigoid Pemphigoid is a group of rare autoimmune blistering diseases of the skin, and mucous membranes. As its name indicates, pemphigoid is similar in general appearance to pemphigus, but, unlike pemphigus, pemphigoid does not feature acantholysis, a l ...

—with very encouraging results of approximately 85% rapid recovery in pemphigus, according to a 2006 study), type 1

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

, Sjögren syndrome,

anti-NMDA receptor encephalitis Anti-NMDA receptor encephalitis is a type of encephalitis, brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with delusions, false b ...

and

Devic's disease Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are autoimmune diseases characterized by acute inflammation of the optic nerve (optic neuritis, ON) and the spinal cord (myelitis). Episodes of ON and myelitis ...

Graves' ophthalmopathy Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and ...

autoimmune pancreatitis Autoimmune Pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. Although autoi ...

Opsoclonus myoclonus syndrome Opsoclonus myoclonus syndrome (OMS), also known as opsoclonus-myoclonus-ataxia (OMA), is a rare neurological disorder of unknown cause which appears to be the result of an autoimmune process involving the nervous system. It is an extremely rare co ...

(OMS), and

IgG4-related disease IgG4-related disease (IgG4-RD), formerly known as IgG4-related systemic disease, is a chronic inflammatory condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, various degrees of fibrosis (scarring) and ...

. There is some evidence that it is ineffective in treating IgA-mediated autoimmune diseases.

Adverse events

Serious adverse events, which can cause death and disability, include: * Severe infusion reaction *

Cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...

* Cytokine release syndrome *

Tumor lysis syndrome Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...

, causing

acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...

* Infections ** Progressive multifocal leukoencephalopathy (PML) caused by JC virus reactivation **

Hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

reactivation ** Other viral infections ** Progressive multifocal leukoencephalopathy (PML) caused by JC virus reactivation * Immune toxicity, with depletion of B cells in 70% to 80% of

patients *

Pulmonary The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...

toxicity *

Bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...

and

perforation A perforation is a small hole in a thin material or web. There is usually more than one perforation in an organized fashion, where all of the holes collectively are called a ''perforation''. The process of creating perforations is called perfor ...

Two patients with

died of progressive multifocal leukoencephalopathy (PML) after being treated with rituximab. PML is caused by activation of JC virus, a common virus in the brain which is usually latent. Reactivation of the JC virus usually results in death or severe brain damage. At least one patient with

developed PML after treatment with rituximab. Rituximab has been reported as a possible cofactor in a chronic

hepatitis E Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrel ...

infection in a person with lymphoma. Hepatitis E infection is normally an

acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

infection, suggesting the drug in combination with lymphoma may have weakened the body's immune response to the virus. A major concern with continuous rituximab treatment is the difficulty to induce a proper vaccine response. This was brought into focus during the

COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...

, where persons with

and rituximab treatment had higher risk of severe COVID-19. In persons with rituximab treatment for multiple sclerosis, 9 of 10 patients with B cell counts of 40/µL or more developed protective levels of antibodies after vaccination with tozinameran.

Mechanisms of action

The antibody binds to the cell surface protein

. CD20 is widely expressed on B cells, from early pre-B cells to later in differentiation, but it is absent on terminally differentiated

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...

s. Although the function of CD20 is unknown, it may play a role in Ca²⁺ influx across plasma membranes, maintaining intracellular Ca²⁺ concentration and allowing activation of B cells. Rituximab is relatively ineffective in elimination of cells with low CD20 cell-surface levels. It tends to stick to one side of B cells, where CD20 is, forming a cap and drawing proteins over to that side. The presence of the cap changes the effectiveness of natural killer (NK) cells in destroying these B cells. When an NK cell latched onto the cap, it had an 80% success rate at killing the cell. In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time. The following effects have been found: * The Fc portion of rituximab mediates

antibody-dependent cellular cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose ...

(ADCC) and

complement-dependent cytotoxicity Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell (e.g. bacterial or viral infected cell), the classical complement pathway is triggered by bonding protei ...

(CDC). * Rituximab has a general regulatory effect on the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

. * Preferential elimination of malignant B cells with high CD20 levels and high BCR signaling propensity, especially in chronic lymphocytic leukemia (CLL). * It increases

MHC II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...

and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen). * It elicits shedding of

CD23 CD23, also known as Fc epsilon RII, or FcεRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 ...

. * It downregulates the

B cell receptor The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...

. * It induces

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

of CD20+ cells. * Rituximab also induces a release of some chronic lymphocytic leukemia cells from immune niches, which might make them more sensitive to chemotherapy used in combination with an anti-CD20 antibody. The combined effect results in the elimination of B cells (including the cancerous ones) from the body, allowing a new population of healthy B cells to develop from lymphoid

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s. Rituximab binds to

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s 170–173 and 182–185 on CD20, which are physically close to each other as a result of a

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

between amino acids 167 and 183.

History

Rituximab was developed by IDEC Pharmaceuticals under the name IDEC-C2B8. The U.S. patent for the drug was issued in 1998 and expired in 2015.DrugBank DB00073
Based on its safety and effectiveness in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s, rituximab was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

in 1997 to treat B-cell

s resistant to other

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

regimens. Rituximab, in combination with CHOP chemotherapy, is superior to CHOP alone in the treatment of

and many other B-cell lymphomas. In 2010, it was approved by the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

for maintenance treatment after initial treatment of

. It is on the

. In 2014, Genentech reclassified rituxan as a

specialty drug Specialty drugs or specialty pharmaceuticals are a recent designation of pharmaceuticals that are classified as high-cost, high complexity and/or high touch. Specialty drugs are often biologics—"drugs derived from living cells" that are injectab ...

, a class of drugs that are only available through specialty distributors in the US. Because wholesalers discounts and rebates no longer apply, hospitals would pay more. Originally available for intravenous injection (e.g. over 2.5 hrs), in 2016, it gained EU approval in a formulation for subcutaneous injection for B-cell CLL/lymphoma (CLL).

Society and culture

Economics

Patents on the drug expired in Europe in February 2013, and in the US in September 2016. , several

biosimilar A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved ...

s had been approved in the US, India, the European Union, Switzerland, Japan and Australia. The US FDA approved Truxima (rituximab-abbs) in 2018, Ruxience (rituximab-pvvr) in 2019 and Riabni (rituximab-arrx) in 2020. The latter is about $3600 per 500 mg, wholesale, list.

Research

Chronic fatigue syndrome

Rituximab did not improve symptoms in patients with

chronic fatigue syndrome Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The causes and mechanisms of the disease are not fully understood. Distinguishing core symptoms are ...

in a trial published in 2019. 22% of participants had serious events. This potential use was investigated after improvements in chronic fatigue syndrome was seen in two cancer patients treated with rituximab.

Intrathecal

For CNS diseases, rituximab could be administered

intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain man ...

ly and this possibility is under study.

Other anti-CD20 monoclonals

The efficacy and success of rituximab has led to some other anti-CD20 monoclonal antibodies being developed: *

ocrelizumab Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti- CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug. ...

, humanized (90%-95% human) B cell-depleting agent. *

ofatumumab Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Unio ...

(HuMax-CD20) a fully human B cell-depleting agent. * Third-generation anti-CD20s such as

obinutuzumab Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody, originated by GlycArt Biotechnology AG and developed by Roche as a cancer treatment. It can be used as a first-line treatment for chronic ly ...

have a glycoengineered Fc fragment (Fc) with enhanced binding to Fc gamma receptors, which increase ADCC (

). This strategy for enhancing a monoclonal antibody's ability to induce ADCC takes advantage of the fact that the displayed Fc glycan controls the antibody's affinity for Fc receptors.

References

External links

* * {{Portal bar, Medicine Genentech brands Hoffmann-La Roche brands Monoclonal antibodies for tumors Orphan drugs Specialty drugs World Health Organization essential medicines Wikipedia medicine articles ready to translate