Infliximab
Overview
 
Infliximab is a monoclonal antibody against tumour necrosis factor alpha (TNFα). It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc. (formerly Centocor
Centocor
Janssen Biotech, Inc., formerly Centocor Biotech, Inc., is a biotechnology company that was founded in Philadelphia in 1979 with an initial goal of developing new diagnostic assays using monoclonal antibody technology....

 Biotech, Inc.) in the USA, Mitsubishi Tanabe Pharma in Japan, Xian Janssen in China, and Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...

 (now part of Merck & Co) elsewhere.

Infliximab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 and ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

.
Encyclopedia
Infliximab is a monoclonal antibody against tumour necrosis factor alpha (TNFα). It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc. (formerly Centocor
Centocor
Janssen Biotech, Inc., formerly Centocor Biotech, Inc., is a biotechnology company that was founded in Philadelphia in 1979 with an initial goal of developing new diagnostic assays using monoclonal antibody technology....

 Biotech, Inc.) in the USA, Mitsubishi Tanabe Pharma in Japan, Xian Janssen in China, and Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...

 (now part of Merck & Co) elsewhere.

Infliximab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 and ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

. Infliximab won its initial approval by the FDA for the treatment of Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

 in August 1998.

Infliximab works by binding to tumour necrosis factor alpha. TNFα is a chemical messenger (cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

) and a key part of the autoimmune reaction. Originally, it was assumed that infliximab works by blocking the action of TNFα by preventing it from binding to its receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 in the cell, and for the action of infliximab in rheumatoid arthritis. This still seems to be true. However, another TNFα-neutralizing medication, etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...

 (Enbrel), is worse than a placebo in Crohn's disease and thus TNFα-neutralisation is not responsible for its powerful action in the latter disease. As infliximab causes programmed cell death of TNFα-expressing activated T lymphocytes, an important cell type mediating inflammation, but etanercept does not have this activity, now it is generally assumed that resolution of activated T cells by infliximab explains its efficacy in Crohn's disease.

Infliximab is an artificial antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

. It was originally developed in mice, as a mouse antibody. Because humans have immune reactions to mouse proteins, it was later developed into a human (humanized) antibody. Because the antibodies were produced from one cell that was grown into a clone of identical cells, it is called a monoclonal antibody. Because it is a combination of mouse and human antibody, it is called a chimeric monoclonal antibody.

Infliximab was developed by Junming Le and Jan Vilcek
Jan Vilcek
Jan T. Vilček M.D., Ph.D. is a biomedical scientist, educator, inventor and philanthropist. He is currently a professor in the Department of Microbiology at the New York University School of Medicine and President of The Vilcek Foundation....

 at New York University School of Medicine
New York University School of Medicine
The New York University School of Medicine is one of the graduate schools of New York University. Founded in 1841 as the University Medical College, the NYU School of Medicine is one of the foremost medical schools in the United States....

 and developed by Centocor
Centocor
Janssen Biotech, Inc., formerly Centocor Biotech, Inc., is a biotechnology company that was founded in Philadelphia in 1979 with an initial goal of developing new diagnostic assays using monoclonal antibody technology....

, (now Jannsen Biotech, Inc.)

Infliximab can cost $19,000 to $22,000 a year per patient wholesale, according to Centocor. Infliximab is typically covered under major medical insurance (rather than prescription drug insurance).

Other monoclonal antibodies targeting TNFα are golimumab
Golimumab
Golimumab is a human monoclonal antibody which is used as an immunosuppressive drug and marketed under the brand name Simponi. Golimumab targets tumor necrosis factor alpha , a pro-inflammatory molecule and hence is a TNF inhibitor....

 (Simponi), adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...

 (Humira), and certolizumab pegol
Certolizumab pegol
Certolizumab pegol is a therapeutic monoclonal antibody produced by UCB for the treatment of Crohn's disease and rheumatoid arthritis.-Method of action:...

 (Cimzia). Etanercept also binds and inhibits the action of TNFα but is not a monoclonal antibody (it is instead a fusion of TNF-receptor
CD120
CD120 , also known as the tumor necrosis factor receptor . This protein is a member of the tumor necrosis factor receptor superfamily.- Receptor subtypes :...

 and an antibody constant region).

Infliximab is administered by intravenous infusion
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...

, typically at 6-8 week intervals, and at a clinic or hospital. It cannot be administered orally
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...

, because the digestive system would destroy the drug.

Pharmacology

According to product labeling, Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNFα and inhibits or prevents the effective binding of TNFα with its receptors. Infliximab and adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...

 (another TNF antagonist) are in the subclass of "anti-TNF antibodies" (they are in the form of naturally occurring antibodies), and are capable of neutralizing all forms (extracellular, transmembrane, and receptor-bound) of TNFα. Etanercept, a third TNF antagonist, is in a different subclass (receptor-construct fusion protein), and, because of its modified form, cannot neutralize receptor-bound TNFα. Additionally, the anti-TNF antibodies adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...

 and infliximab have the capability of lysing cells involved in the inflammatory process, whereas the receptor fusion protein apparently lacks this capability. Although the clinical significance of these differences have not been absolutely proven, they may account for the differential actions of these drugs in both efficacy and side effects.

Infliximab has high specificity for TNFα, and does not neutralize TNF beta (TNFβ, also called lymphotoxin
Lymphotoxin
Lymphotoxin is a lymphokine cytokine.It is a protein that is produced by Th1 type T-cells and induces vascular endothelial cells to change their surface adhesion molecules to allow phagocytic cells to bind to them.Lymphotoxin is homologous to Tumor Necrosis Factor beta, but secreted by T-cells...

 α), an unrelated cytokine that uses different receptors from TNFα. Biological activities that are attributed to TNFα include: induction of proinflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s such as interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

 (IL) 1 and IL 6, enhancement of leukocyte movement or migration from the blood vessels into the tissues by increasing the permeability of endothelial layer of blood vessels; and increasing the release of adhesion molecules. Infliximab prevents disease in transgenic mice (a special type of mice that are biologically engineered to produce a human form of TNFα and which are used to test the results of these drugs that might be expected in humans). These experimental mice develop arthritis as a
result of their production of human TNFα, and when administered after disease onset, infliximab allows eroded joints to heal.

Infliximab in Crohn's disease

There are three phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

s, or categories of disease presentation in Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

: stricturing disease (which causes narrowing of the bowel), penetrating disease (which causes fistula
Fistula
In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...

e or abnormal connections of the bowel), and inflammatory disease (which causes primarily inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

).

Fistulizing disease

Infliximab was first used for closure of fistulae in Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

 in 1999. In a 94-patient phase II clinical trial, the researchers showed that infliximab was effective in closing fistulae between the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

 and bowel in 56-68% of patients. A large 296-patient Phase III clinical trial called the ACCENT 2 trial, showed that infliximab was additionally beneficial in maintaining closure of fistulae, with almost two-thirds of all patients treated with the 3 initial doses infliximab having a fistula response after 14 weeks, and 36% of patients maintaining closure of fistulae after a year, compared with 19% who received placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

 therapy. This final trial resulted in the FDA approval of the drug to treat fistulizing disease.

Inflammatory disease

Infliximab has also been used in order to induce and maintain remission in inflammatory Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

. The ACCENT 1 trial was a large multicentre trial that showed that 39 to 45% of patients treated with infliximab who had an initial response to it, maintained remission after 30 weeks, compared with 21% who received placebo treatment. It also showed a mean maintenance of remission from 38 to 54 weeks compared with 21 weeks for patients who received placebo treatment.

Crohn's patients have flares of their disease between periods of disease quiescence. Severe flares are usually treated with steroid
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

 medications to obtain remission, but steroids have many undesirable side effects, and therefore some gastroenterologists are now advocating for the use of infliximab as the first drug to try to get patients into remission. This has been called the top-down approach to treatment.

Infliximab in ulcerative colitis

Infliximab targets TNF, thought to be more related to Th1 cytokines. Ulcerative colitis was thought to be a Th2 disease, and Infliximab of limited use. However, patients with ulcerative colitis have begun to be treated with infliximab on the basis of two large clinical trials conducted in 2005 by Paul Rutgeerts and William Sandborn. The ACT 1 and ACT 2 (Acute ulcerative Colitis Treatment) trials evaluated the utility of infliximab in ulcerative colitis and showed that 44-45% of patients treated with infliximab for a year maintained a response to the medication, compared with 21% of patients who were treated with placebo medication. At 2 months, the response was 61-69% for patients treated with infliximab, and 31% for those who were treated with placebo.

Safety

According to the product labeling of infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), these drugs are in the class of immunosuppressants. A number of studies and reports of adverse and serious adverse reactions in patients receiving infliximab have been conducted. Risks include:
  • serious and sometimes fatal blood disorders
  • serious infection
    Infection
    An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

    s
  • lymphoma
    Lymphoma
    Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

     and solid tissue cancers
  • reports of serious liver injury
  • reactivation of hepatitis B
  • reactivation of tuberculosis
    Tuberculosis
    Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

  • lethal hepatosplenic T-cell lymphoma
    Hepatosplenic T-cell lymphoma
    Hepatosplenic T-cell lymphoma is a rare and generally incurable form of lymphoma.- Definition :Hepatosplenic T-cell lymphoma is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liver, spleen, and bone marrow.- Epidemiology :This...

     (Generally only when combined with 6-mercaptopurine)
  • drug-induced lupus
    Lupus
    Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...

  • demyelinating central nervous system
    Central nervous system
    The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

     disorders


Cases of leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....

, neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...

, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

, and pancytopenia
Pancytopenia
Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.If only two parameters from the full blood count are low, the term bicytopenia can be used...

 (some fatal) have been reported with infliximab. The FDA issued a warning to doctors appearing in the respective product labeling of infliximab instructing them to screen and monitor potential patients more carefully. The FDA issued a warning to doctors that there is an increased risk of lymphoma and other cancers associated with the use of infliximab and other tumor necrosis factor
Tumor necrosis factor
Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction...

 (TNF) blockers in children and adolescents.

Maintenance therapy with the drug (versus intermittent or sporadic therapy) lessens the likelihood of developing antibodies to infliximab which are known to reduce the efficacy of the drug. Combination treatment with methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...

 (an anti-folate drug which suppresses the immune system) has been shown to reduce the formation of these antibodies in patients with rheumatoid arthritis and combination therapy with other immunosuppressants has been shown to reduce the likelihood of these antibodies being formed in Crohn's disease. The use of immunosuppressants may not be necessary in all diseases for which infliximab is indicated, and indiscriminant use of these other immunosuppressants carry their own risks. Infliximab was studied in monotherapy (without concomitant immunosuppressants such as methotrexate or azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...

) in psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

, and ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

. Only its use in rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 requires the concomitant use of methotrexate by FDA product labeling; however, the concomitant use of methotrexate in other disease states may help to reduce the body's immune response to the infliximab and increase its duration of efficacy.

Other uses

Case studies have been done into other uses of infliximab, such as to treat skin diseases. Infliximab was approved for treating ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, fistulizing Crohn's disease, pediatric Crohn's disease, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

, psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, and ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

. Infliximab is also prescribed (out of indication) for the treatment of Behçet's disease
Behçet's disease
Behçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements...

, and infusions of infliximab have been used successfully in the treatment of sciatica
Sciatica
Sciatica is a set of symptoms including pain that may be caused by general compression or irritation of one of five spinal nerve roots that give rise to each sciatic nerve, or by compression or irritation of the left or right or both sciatic nerves. The pain is felt in the lower back, buttock, or...

 due to slipped discs.

There have been numerous case reports of the efficacy of infliximab in various inflammatory skin conditions diseases; psoriasis, in which increased TNFα has been demonstrated, is the most recent indication.

Psoriatic arthritis (PsA), a chronic systemic inflammatory disorder characterized by the association of arthritis and psoriasis, follows a heterogeneous and variable clinical course. Inhibitors of TNF, such as infliximab, substantially improve the signs and symptoms of psoriasis (level 1b, grade A). Several therapies with modest efficacy have been studied in nail psoriasis. Among available agents, higher quality data are available to support the efficacy of cyclosporine and infliximab, a TNF antagonist. Based on studies in AS, the results suggest that infliximab, etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...

, and adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...

 have the potential to reduce the signs and symptoms of moderate to severely active axial involvement in PsA in patients who have had an inadequate response to NSAID (level 1a, grade A). The anti-TNF agents (infliximab and etanercept; level 1b, grade A) are more effective for the treatment of enthesitis
Enthesitis
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or...

 than traditional agents. Results suggest that infliximab is effective for the treatment of dactylitis in PsA (level 1b, grade B).

Availability/affordability

Like all of the TNF inhibitors, infliximab is an expensive medication, costing about US$900 for a 100 mg dose, and is covered by almost every medical insurance plan (though caps on many plans make it possible to be covered for only a subset of treatments in the course of a year). Infliximab is supplied as a sterile, white, lyophilized (freeze dried) powder and must be reconstituted and administered by a health care professional, usually in a hospital or office setting. For this reason it is usually covered under major medical insurance rather than prescription drug coverage.

According to the labeling, the current dosing is:
  • Ankylosing spondylitis
    Ankylosing spondylitis
    Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

    : 5 mg per kg
  • Crohn's disease
    Crohn's disease
    Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

    : 5 mg per kg
  • Psoriatic arthritis
    Psoriatic arthritis
    Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

    : 5 mg per kg
  • Rheumatoid arthritis
    Rheumatoid arthritis
    Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

    : 3 mg per kg
  • Psoriasis
    Psoriasis
    Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

    : 5 mg per kg


The loading regimen for all approved indications occurs at weeks 0, 2, and 6 at the above dosages.

Infliximab is available from the NHS in the UK for Crohn's disease treatment provided three criteria are met. Patients should have severe active Crohn's disease with a CDAI
Crohn's Disease Activity Index
The Crohn's Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. This is of importance in research studies done on medications used to treat Crohn's disease; most major studies on newer medications use the CDAI in order to define...

score of 300 or more, have not responded to immunomodulating drugs and corticosteroids, and for whom surgery is inappropriate.

Infliximab is available through the PBS in Australia for Crohn's disease treatment provided that the patient has not responded to conventional treatment and is suffering from a severe case of the condition.

Infliximab is available in the Republic of Ireland through the HSE's Medical Card and Drug Payment Scheme.

External links

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