Anakinra
Encyclopedia
Anakinra is a drug
used to treat rheumatoid arthritis
.
. Anakinra blocks the biologic activity of naturally occurring IL-1, including inflammation
and cartilage degradation associated with rheumatoid arthritis
, by competitively inhibiting the binding of IL-1 to the Interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory
and immunologic reactions. IL-1 additionally stimulates bone resorption
and induces tissue damage like cartilage degradation as a result of loss of proteoglycans. In patients with rheumatoid arthritis the natural IL-1 receptor antagonist is not found in effective concentrations in synovium
and synovial fluid
to counteract the elevated IL-1 concentrations in these patients.
Anakinra is not considered a 'Disease-modifying antirheumatic drug
' (DMARD) but rather a 'Biological Response Modifier' (BRM) because its able to selectively target the pathologic element of the disease.
using recombinant DNA technology. It consists of 153 amino acids and has a molecular weight of 17,257.6 g/mol (approx. 17.3 kilodaltons) and differs from native human IL-1RA in that it has the addition of a single methionine residue on its amino terminus.
Anakinra had an absolute bioavailability of 95% for healthy adults (n = 11) after a 70 mg subcutaneous bolus injection. Peak plasma concentrations of anakinra generally occurred 3 to 7 hours after s.c. administration of clinically relevant doses (1 to 2 mg/kg: n = 18) for patients with rheumatoid arthritis. The terminal half-life ranged from 4 to 6 hours. After daily s.c. dosing for up to 24 weeks, no unexpected accumulations of anakinra were observed in the plasma samples of rheumatoid arthritis patients.
This drug is sold under the tradename "Kineret" and is produced by the pharmaceutical company Amgen
. Since 15 December 2008 Swedish Orphan Biovitrum AB is the global Market Authorisation Holder for Kineret on the indication adult rheumatoid arthritis. It is delivered as injection concentrate containing 100 mg each single dose.
(Enbrel), infliximab
(Remicade) or adalimumab
(Humira).
Anakinra showed moderate but statistically significant therapeutic efficacy; in most studies methotrexate
was administered concomitantly. In the methotrexate plus anakinra group 38% of 250 patients reached an improvement/relief of symptoms of at least 20% within 24 weeks. In the control group of 251 patients under methotrexate treatment alone response was seen in 22% only. The clinical response was measured according to ACR-criteria (20, 50, and 70).
There are no direct studies comparing anakinra with TNF-α inhibitors, but indirect data suggests that anakinra may be inferior to TNF-α inhibitors. In a study with infliximab plus methotrexate 50% of all patients had significant remission (according to at least ACR 20 criteria) after a 30-week treatment period.
Precautions:
(WHO) toxicity grade compared with 2% in the placebo control group. anakinra-treated patients experienced defined neutropenia (ANC < 1 x 109/L) in 0.4%.
Neutrophil counts should be assessed prior to initiating anakinra treatment, and while receiving anakinra, monthly for 3 months, and thereafter quarterly for a period up to 1 year.
Additionally, 37 solid tumors of different origination have been found. Of these, the number of 3 melanomas reported in study 4 is significant (1 case expected), but the clear association to anakinra therapy remains unclear.
The Cochrane Collaboration (www.cochrane.org) is an independent body which produces systematic literature reviews to a high academic standard. The Cochrane review entitled, ‘Anakinra for rheumatoid arthritis’ (Mertens and Singh, 2009; http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD005121/pdf_standard_fs.html) evaluates the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis, using data from 2876 patients, from five trials which constituted in total 781 randomized to placebo and 2065 to anakinra. The authors conclude, “There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively”. These injection site reactions last for no more than four months and are not serious. Each of the trials reviewed measured prevalence of malignancies and found no evidence that these are increased amongst patients taking anakinra.
An increased incidence of serious infections and an increased risk of neutropenia have been seen when anakinra and etanercept were used concomitantly in patients with rheumatoid arthritis. Similar interactions can be anticipated for the combination therapy of anakinra together with other agents blocking TNF (alpha) (e.g., adalimumab, infliximab). Therefore, combined drug therapy with anakinra and any TNF-blocking agent is not recommended and should be avoided. Moreover, in a 24-week clinical study a regime with anakinra and etanercept did not provide any additional benefit to the patients.
Methotrexate has been coadministered with anakinra in quite extended clinical studies. Neither specific drug interactions nor increased toxicity of anakinra and/or methotrexate have been noticed. In animal models (rats) studying the effects of both drugs when coadminstered, no effects on clearing of both drugs form plasma or on the respective toxicologic properties have been seen. Therefore, the concomitant use of both disease modifiers in patients with rheumatoid arthritis can be regarded as safe.
Live-virus vaccines should not be given to patients during anakinra treatment. Information is not available, if anakinra would affect the rate of secondary transmission of vaccine virus (e.g., measles or poliomyelitis viruses) following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug. Due to the fact that anakinra decreases the immune response to antigens in general, vaccine efficacy may be reduced in patients receiving anakinra.
, and spondylarthritis. Possibly, anakinra may even benefit patients with destructive osteoarthritis
in inflammatory phases. Anakinra may also be effective in pediatric patients with juvenile rheumatoid arthritis (JRA). Clinical studies have not been initiated so far regarding these diseases. Currently, the use of anakinra in these patients is therefore not recommended.
On April 12, 2007 an article in the New England Journal of Medicine
discussed the possibility of using anakinra for treatment of type 2 diabetes. A few studies have looked at the effectiveness of anakinra in some familial periodic fever syndrome
s.
On May 2, 2008 an article in the review Science
discussed the possibility of using anakinra for treatment of asbestosis
.
"Since Anakinra (IL-1ra) is efficiently used in the clinical treatment of autoinflammatory
syndromes as well as gout patients, the present study suggests a potential use of
Anakinra in order to slow down progression of asbestosis, silicosis and possibly other
inflammatory lung diseases."
There is anecdotal evidence suggesting that IL-1 inhibitors may indeed be effective in gouty arthritis,and this approach is currently under study.
In 2008, an article in the European Journal of Pediatrics discussed treatment of colchicine
-resistant Familial Mediterranean Fever
with anakinra.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
used to treat 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...
.
Mechanism
Anakinra is an interleukin-1 (IL-1) receptor antagonistReceptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. Anakinra blocks the biologic activity of naturally occurring IL-1, including 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...
and cartilage degradation associated with 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...
, by competitively inhibiting the binding of IL-1 to the Interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory
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...
and immunologic reactions. IL-1 additionally stimulates bone resorption
Bone resorption
Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood....
and induces tissue damage like cartilage degradation as a result of loss of proteoglycans. In patients with rheumatoid arthritis the natural IL-1 receptor antagonist is not found in effective concentrations in synovium
Synovium
Synovial membrane is the soft tissue found between the articular capsule and the joint cavity of synovial joints....
and synovial fluid
Synovial fluid
Synovial fluid is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its yolk-like consistency , the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.-Overview:The inner membrane of synovial joints...
to counteract the elevated IL-1 concentrations in these patients.
Anakinra is not considered a 'Disease-modifying antirheumatic drug
Disease-modifying antirheumatic drug
Disease-modifying antirheumatic drugs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression...
' (DMARD) but rather a 'Biological Response Modifier' (BRM) because its able to selectively target the pathologic element of the disease.
Basic chemical, pharmacological, and marketing data
The anakinra molecule is a recombinant, non-glycosylated version of human IL-1RA (RA for receptor antagonist)prepared from cultures of genetically modified Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
using recombinant DNA technology. It consists of 153 amino acids and has a molecular weight of 17,257.6 g/mol (approx. 17.3 kilodaltons) and differs from native human IL-1RA in that it has the addition of a single methionine residue on its amino terminus.
Anakinra had an absolute bioavailability of 95% for healthy adults (n = 11) after a 70 mg subcutaneous bolus injection. Peak plasma concentrations of anakinra generally occurred 3 to 7 hours after s.c. administration of clinically relevant doses (1 to 2 mg/kg: n = 18) for patients with rheumatoid arthritis. The terminal half-life ranged from 4 to 6 hours. After daily s.c. dosing for up to 24 weeks, no unexpected accumulations of anakinra were observed in the plasma samples of rheumatoid arthritis patients.
This drug is sold under the tradename "Kineret" and is produced by the pharmaceutical company Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
. Since 15 December 2008 Swedish Orphan Biovitrum AB is the global Market Authorisation Holder for Kineret on the indication adult rheumatoid arthritis. It is delivered as injection concentrate containing 100 mg each single dose.
Indications
Anakinra is indicated for the management of signs and symptoms of rheumatoid arthritis and to inhibit the progression of structural damage associated with the disease in adults with moderately to severely active disease who have had an absence of clinical improvement of symptoms or inadequate response in therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs). It is used as monotherapeutic agent or in combination with DMARDs. Anakinra should not be used in combination with anti-TNF agents such as etanerceptEtanercept
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), infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
(Remicade) or 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).
Anakinra showed moderate but statistically significant therapeutic efficacy; in most studies 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...
was administered concomitantly. In the methotrexate plus anakinra group 38% of 250 patients reached an improvement/relief of symptoms of at least 20% within 24 weeks. In the control group of 251 patients under methotrexate treatment alone response was seen in 22% only. The clinical response was measured according to ACR-criteria (20, 50, and 70).
There are no direct studies comparing anakinra with TNF-α inhibitors, but indirect data suggests that anakinra may be inferior to TNF-α inhibitors. In a study with infliximab plus methotrexate 50% of all patients had significant remission (according to at least ACR 20 criteria) after a 30-week treatment period.
Contraindications and precautions
- HypersensitivityHypersensitivityHypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
to anakinra, other E. coli derived proteins, or to any other ingredient (absolute contraindication). - Preexisting malignant diseases (e.g., solid cancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s, leukemiaLeukemiaLeukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
): absolutely contraindicated (anakinra may be a human carcinogen and the suppression of immune function may worsen already existing malignancies). - Patients with neutropeniaNeutropeniaNeutropenia, 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...
due to any reason : absolutely contraindicated. Neutrophil counts should be obtained before initiating therapy and regularly thereafter (see recommended laboratory tests). - Severely impaired renal functionRenal functionRenal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
(creatinine clearance less than 30 ml/minute): absolutely contraindicated. - Preexisting active tuberculosisTuberculosisTuberculosis, 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...
(disease may be worsened – see side-effects). - Concomitant application of live-virus vaccines (see Interactions).
- LactationLactationLactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
: it is unknown if anakinra is distributed into human milk. Nursing mothers should either discontinue the drug or breast-feeding, taking into account the importance of the drug to the mother. - Pediatric patients: no well controlled human data exists in patients under age 18. Therefore, therapy is contraindicated in those patients.
Precautions:
- Geriatric patients (over 65 yrs of age): risk of infections is increased.
- AsthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
: increased risk of severe infections. - Women of childbearing potential should use effective contraceptionContraceptionContraception is the prevention of the fusion of gametes during or after sexual activity. The term contraception is a contraction of contra, which means against, and the word conception, meaning fertilization...
methods. - Pregnancy: animal studies showed no adverse effects. Human data is not available. The drug should be applied to pregnant women only if clearly indicated.
- Mild to moderately impaired renal function: caution.
Side-effects
- GITGastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
: Frequently, nausea (8%), diarrhea (7%), unspecific abdominal pain (5%). - AllergyAllergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
: Rare cases of allergic reactions including severe anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
have been noticed. If necessary, the usual symptomatic therapy with corticosteroids, epinephrineEpinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, antihistaminics and i.v. fluid correction should be initiated as soon as possible. Rare cases of allergic skin rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
have also been seen. - Respiratory tractRespiratory tractIn humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
: Frequently, infections of upper respiratory tract (13%), sinusitisSinusitisSinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
(7%), flu-like syndrome (6%), Infrequently, pneumoniaPneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
and tuberculosisTuberculosisTuberculosis, 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...
. - SkinSkin-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...
: Frequently ecchymoses, infrequently skin mycosisMycosisA mycosis is a fungal infection of animals, including humans. Mycoses are common, and a variety of environmental and physiological conditions can contribute to the development of fungal diseases...
, Lupus-erythematosis-like syndrome, urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, and isolated cases of melanoma (see malignancies). - Immune systemImmune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
: Frequently, infections (40%, severe in 2%). Infrequently, production of antibodies with neutralizing activity. - Blood and blood forming organs : Frequently, decrease in neutrophil counts (8% under anakinra, placebo 2%), infrequent significant neutropenia (0.4% under anakinra), moderate eosinophiliaEosinophiliaEosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
, moderate thrombocytopeniaThrombocytopeniaThrombocytopenia 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 malignant lymphomaLymphomaLymphoma 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...
s (0.12 cases/patient year) (see malignancies). - Musculosceletal system : Infrequent are arthritic symptoms, arthritic symptoms associated with inflammation, bony infections.
- Pain, inflammation, and erythema at injection sites : Very frequently (70% of patients), usually during first 4 weeks of therapy, reversible within 1 to 2 weeks. These reactions are reasons why many patients discontinue therapy.
Recommended Laboratory Tests
In patients receiving anakinra a decrease in neutrophil counts may be found. In the placebo-controlled studies 8% of patients receiving anakinra had decreases in neutrophil counts of at least 1 World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) toxicity grade compared with 2% in the placebo control group. anakinra-treated patients experienced defined neutropenia (ANC < 1 x 109/L) in 0.4%.
Neutrophil counts should be assessed prior to initiating anakinra treatment, and while receiving anakinra, monthly for 3 months, and thereafter quarterly for a period up to 1 year.
Malignancies
Among 5,300 rheumatoid arthritis patients treated with anakinra in clinical trials for a mean of 15 months (approximately 6,400 patient years of treatment), 8 cases of lymphomas were observed resulting in a rate of 0.12 cases/100 patient years. This is 3.6 fold higher than the rate of lymphomas expected in the general population. However, the 'natural' incidence of lymphomas in patients with rheumatoid arthritis is considerably increased and may even be higher in patients with high disease activity.Additionally, 37 solid tumors of different origination have been found. Of these, the number of 3 melanomas reported in study 4 is significant (1 case expected), but the clear association to anakinra therapy remains unclear.
The Cochrane Collaboration (www.cochrane.org) is an independent body which produces systematic literature reviews to a high academic standard. The Cochrane review entitled, ‘Anakinra for rheumatoid arthritis’ (Mertens and Singh, 2009; http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD005121/pdf_standard_fs.html) evaluates the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis, using data from 2876 patients, from five trials which constituted in total 781 randomized to placebo and 2065 to anakinra. The authors conclude, “There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively”. These injection site reactions last for no more than four months and are not serious. Each of the trials reviewed measured prevalence of malignancies and found no evidence that these are increased amongst patients taking anakinra.
Interactions
- TNF-Blocking Agents:
An increased incidence of serious infections and an increased risk of neutropenia have been seen when anakinra and etanercept were used concomitantly in patients with rheumatoid arthritis. Similar interactions can be anticipated for the combination therapy of anakinra together with other agents blocking TNF (alpha) (e.g., adalimumab, infliximab). Therefore, combined drug therapy with anakinra and any TNF-blocking agent is not recommended and should be avoided. Moreover, in a 24-week clinical study a regime with anakinra and etanercept did not provide any additional benefit to the patients.
- Methotrexate:
Methotrexate has been coadministered with anakinra in quite extended clinical studies. Neither specific drug interactions nor increased toxicity of anakinra and/or methotrexate have been noticed. In animal models (rats) studying the effects of both drugs when coadminstered, no effects on clearing of both drugs form plasma or on the respective toxicologic properties have been seen. Therefore, the concomitant use of both disease modifiers in patients with rheumatoid arthritis can be regarded as safe.
- Vaccines:
Live-virus vaccines should not be given to patients during anakinra treatment. Information is not available, if anakinra would affect the rate of secondary transmission of vaccine virus (e.g., measles or poliomyelitis viruses) following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug. Due to the fact that anakinra decreases the immune response to antigens in general, vaccine efficacy may be reduced in patients receiving anakinra.
Dosage regimen
The usual dosage is 100 mg subcutaneosly (s.c.) once a day. Dose reduction to 100 mg s.c. every other day should be considered in patients with severe renal impairment, if these are treated in exceptional cases (see contraindications and precautions). No additional benefits of doses exceeding 100 mg daily have been seen.Duration of treatment
In the pre-clinical and clinical studies the usual duration of therapy was 24 weeks. It is possible to extend therapy to 48 weeks in patients with satisfying remission after 24 weeks to maintain clinically evident improvements. Under continued therapy anakinra has been shown to slow progression of disease over a period of at least 12 month evidenced by X-ray studies or other clinical examinations. Some experience with 48 to 60 weeks (15 months) treatment duration has already been gained and no evidence has been seen regarding additional toxicity.Possible future indications
Due to the specific mechanism of action of anakinra, a possible efficiency may be anticipated in patients with inflammatory joint diseases such as psoriatic arthritisPsoriatic 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 spondylarthritis. Possibly, anakinra may even benefit patients with destructive osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
in inflammatory phases. Anakinra may also be effective in pediatric patients with juvenile rheumatoid arthritis (JRA). Clinical studies have not been initiated so far regarding these diseases. Currently, the use of anakinra in these patients is therefore not recommended.
On April 12, 2007 an article in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
discussed the possibility of using anakinra for treatment of type 2 diabetes. A few studies have looked at the effectiveness of anakinra in some familial periodic fever syndrome
Periodic fever syndrome
The periodic fever syndromes are a set of disorders, many of which are genetic disorders in which the mechanisms which initiate and control inflammation are disturbed, leading to uncontrolled inflammation throughout the body...
s.
On May 2, 2008 an article in the review Science
Science
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe...
discussed the possibility of using anakinra for treatment of asbestosis
Asbestosis
Asbestosis is a chronic inflammatory and fibrotic medical condition affecting the parenchymal tissue of the lungs caused by the inhalation and retention of asbestos fibers...
.
"Since Anakinra (IL-1ra) is efficiently used in the clinical treatment of autoinflammatory
syndromes as well as gout patients, the present study suggests a potential use of
Anakinra in order to slow down progression of asbestosis, silicosis and possibly other
inflammatory lung diseases."
There is anecdotal evidence suggesting that IL-1 inhibitors may indeed be effective in gouty arthritis,and this approach is currently under study.
In 2008, an article in the European Journal of Pediatrics discussed treatment of colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
-resistant Familial Mediterranean Fever
Familial Mediterranean fever
Familial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin....
with anakinra.
External links
- Kineret homepage
- http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/tumorrisiko.html (on the risk of cancerogenity (in German))
- http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/ausblicke-moegliche-zukuenftige-anwendungen-von-anakinra-kineret.html (same site on future indications)
- http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/anakinra-kineret-in-der-kinderrheumatologie.html (same site on possible pediatric indications)