Alefacept

Last updated
Alefacept
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a603011
Pregnancy
category
  • AU:C
Routes of
administration
Intravenous, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 63% (IM)
Elimination half-life ~270 hours
Identifiers
  • 1-92-LFA-3 (Antigen) (human) fusion protein with immunoglobin G1 (human hinge CH2-CH3γ1-chain) dimer
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C2306H3594N610O694S26
Molar mass 51801.25 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Alefacept is a genetically engineered immunosuppressive drug. It was sold under the brand name Amevive in Canada, the United States, Israel, Switzerland and Australia. In 2011, the manufacturers made a decision to cease promotion, manufacturing, distribution and sales of Amevive during a supply disruption. According to Astellas Pharma US, Inc., [1] the decision to cease Amevive sales was neither the result of any specific safety concern nor the result of any FDA-mandated or voluntary product recall. On the other hand, usage of Amevive was associated with a certain risk of development systemic diseases such as malignancies. This drug was never approved for the European drug market.

Contents

Alefacept is used to control inflammation in moderate to severe psoriasis with plaque formation, where it interferes with lymphocyte activation. [2] It is also being studied in the treatment of cutaneous T-cell lymphoma and T-cell non-Hodgkin lymphoma. [3]

Alefacept is a fusion protein: it combines part of an antibody with a protein that blocks the growth of some types of T cells. [3]

Mechanism of action

The mechanism of action involves dual mechanisms. Alefacept inhibits the activation of CD4 + and CD8 + T cells by interfering with CD2 on the T cell membrane thereby blocking the costimulatory molecule LFA-3/CD2 interaction. Another mechanism is inducing apoptosis of memory-effector T lymphocytes. If the T cells were to become activated they would stimulate proliferation of keratinocytes resulting in the typical psoriatic symptoms. Therefore, alefacept leads to clinical improvement of moderate to severe psoriasis by blunting these reactions. Combinations of therapeutic modalities have been utilized to meet the challenge of difficult to treat psoriasis. [4]

Indications

Alefacept is indicated for the management of patients with moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. The concomitant use of low-potency topical corticosteroids was permitted during the treatment phase with alefacept and does not seem to pose any additional risks.

The drug was approved based upon studies involving 1,869 patients altogether with plaques covering at least 10% of body surface. Either 7.5 mg IV or 15 mg IM once a week were applied. The long-term results (reduction of at least 75% in pretreatment PASI scores) were 14% and 21%, respectively. Additional improvements ensuing after completion of the 12-week treatment phase or after completion of a second alefacept treatment were also seen. Often the remissions were maintained for 7 to 12 months after end of treatment.

Contraindications and precautions

Pregnancy and lactation

Pediatric patients

No clinical experience exists in patients under 18 years of age. The drug should therefore not be used in pediatric patients.

Side effects

Interactions

Necessary laboratory examinations

Dosage regimens

The standard dosage regimen is the weekly application of either 7.5 mg IV or 15 mg IM for a course of 12 weeks. The benefits and risks of repeated courses have not been explored in sufficient detail. Therapy should be conducted under the supervision of a physician experienced in the use of immunosuppressant agents.

Withdrawal

Due to availability of better tolerated and more efficacious molecules for psoriasis, alefacept was withdrawn from use by its sponsor in 2011. [5]

Notes

  1. "Archived copy". Archived from the original on 2018-10-13. Retrieved 2017-05-06.CS1 maint: archived copy as title (link)
  2. "New drugs". Australian Prescriber. 27 (101): 5. 2004. Archived from the original on 2006-08-24. Retrieved 2006-08-20.
  3. 1 2 PD-icon.svg This article incorporates  public domain material from the U.S. National Cancer Institute document: "Alefacept".
  4. Scheinfeld N (2005). "Therapy-resistant psoriasis treated with alefacept and subsequent narrow band ultraviolet B phototherapy with total clearing of psoriasis". Dermatol. Online J. 11 (2): 7. PMID   16150215.
  5. "Alefacept", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID   31643667 , retrieved 2021-08-16

Related Research Articles

Psoriasis Skin disease

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, or purple on some people with darker skin, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

Immunosuppressive drug

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.

Methotrexate Chemotherapy and immunosuppressant medication

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy and for medical abortions. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

Infliximab

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

Light therapy Treatment for seasonal affective disorder or exposure of the skin to specific wavelengths of light

Light therapy—or phototherapy, classically referred to as heliotherapy—consists either of exposure to daylight or some equivalent form of light as a treatment for seasonal affective disorder (SAD), or exposure of the skin to specific wavelengths of light using polychromatic polarised light to treat a skin condition.

Ketoconazole Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive hair growth and Cushing's syndrome.

Pimecrolimus

{{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464206673 | IUPAC_name = (3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-3-{(E)-2-[(1R,3R,4S)-4-chloro-3 -methoxycyclohexyl]-1-methylvinyl}-8-ethyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosin-1,7,20,21(4H,23H)-tetrone | image = Pimecrolimus2DACS.svg | width = 200 | image2 = Pimecrolimus ball-and-stick.png | tradename = Elidel | Drugs.com = Monograph | pregnancy_AU = B3 | pregnancy_US = C | legal_US = Rx-only | routes_of_administration = topical | bioavailability = low systemic absorption | protein_bound = 74%–87% | metabolism = Hepatic CYP3A | elimination_half-life = | excretion = | CAS_number_Ref =   | CAS_number = 137071-32-0 | ATC_prefix = D11 | ATC_suffix = AH02 | PubChem = 16051947 | DrugBank_Ref =  

| DrugBank = DB00337

PUVA is an ultraviolet light therapy treatment for skin diseases: eczema, psoriasis, graft-versus-host disease, vitiligo, mycosis fungoides, large plaque parapsoriasis and cutaneous T-cell lymphoma using the sensitizing effects of the drug psoralen. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA.

Cyclophosphamide Medication used as chemotherapy and to suppress the immune system

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, small cell lung cancer, neuroblastoma, and sarcoma. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis, and following organ transplant, among other conditions. It is taken by mouth or injection into a vein.

Cladribine

Cladribine, sold under the brand names Leustatin among others, is a medication used to treat hairy cell leukemia and B-cell chronic lymphocytic leukemia.

Febrile neutrophilic dermatosis Medical condition

Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a skin disease characterized by the sudden onset of fever, an elevated white blood cell count, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination.

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, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

Ustekinumab, sold under the brand name Stelara®, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

Marginal zone B-cell lymphoma Group of lymphomas

Marginal zone B-cell lymphomas, also known as marginal zone lymphomas (MZLs), are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. Marginal zone B cells are innate lymphoid cells that normally function by rapidly mounting IgM antibody immune responses to antigens such as those presented by infectious agents and damaged tissues. They are lymphocytes of the B-cell line that originate and mature in secondary lymphoid follicles and then move to the marginal zones of mucosa-associated lymphoid tissue, the spleen, or lymph nodes. Mucosa-associated lymphoid tissue is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as the gastrointestinal tract, mouth, nasal cavity, pharynx, thyroid gland, breast, lung, salivary glands, eye, skin and the human spleen.

Tofacitinib medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.

Secukinumab Monoclonal antibody against IL-17 used for treatment of psoriasis

Secukinumab, sold under the brand name Cosentyx, is a human IgG1κ monoclonal antibody that binds to the protein interleukin (IL)-17A, and is marketed by Novartis for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It inhibits a member of the cytokine family, interleukin 17A.

Apremilast

Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. It may also be useful for other immune system-related inflammatory diseases. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.

Tildrakizumab is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders. It is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis in the United States and the European Union.

Idelalisib

Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers.