Alefacept (Intramuscular)

Alefacept is a drug that was marketed under the trade name Amevive in quite a few countries, including the United States, for the immunosuppressive

Overview

Immunosuppressive drugs are used to limit the response of the immune system in certain scenarios, and they have been successfully given for a myriad of problems such as transplant rejection, autoimmune diseases, and also non-autoimmune inflammatory diseases. In many cases, the human body will experience immunosuppression without any medication or treatment, and sometimes different parts of the immune system will exercise this type of suppression on another part. However, these drugs that deliberately induce this response can be useful for certain scenarios. Alefacept is one such drug that was marketed by Astellas Pharma US under the brand name of Amevive. There were a couple of areas of interest in regards to its usefulness in medicine. The primary of these use cases was for the inflammation control in patients with psoriasis of the moderate or severe persuasion. It was also investigated for its usefulness in combating a couple of types of lymphoma (both cutaneous T-cell lymphoma and T-cell non-Hodgkin).

It does well as a fusion protein, but in 2011 the company decided to take it off of the market. While this withdrawal was not because of any Federal Drug Administration recall order or specific safety concerns, it was known that some systemic diseases were more likely to occur in those who were taking this medication.

Treated Conditions

  • Cutaneous T-cell Lymphoma
  • T-cell non-Hodgkin Lymphoma
  • Psoriasis (moderate or severe)

Type of Medicine

  • Amevive 15 mg lyophilized powder (supplied with a diluent)

Side Effects

  • Lymphopenia is one of the side effects that manifested in some of the patients who received alefacept. It was seen that in as many as 59% of the patients there was a reduction in the CD4+ and CD8+ counts, but only a small portion of these people had enough of a reduction in their lymphocytes that it was cause for a concern due to being lower than the acceptable threshold. These patients whose lymphocyte count does fall below that lower limit are more prone to infections and other types of malignancies, and so these counts need to be monitored closely both before and after administering the drug. At first, the white blood cell count can be checked at an interval of two weeks to make sure that the level remains feasible. However, if the count comes back too low at any point then there will need to be weekly checks done, but first, the Amevive dosage needs to either be reduced or the therapy discontinued for a period of time to get everything back in order.
  • Malignancies were seen in a small number of the patients who were treated with Alefacept. These usually manifested in the form of skin cancers (both melanoma and nonmelanoma) as well as tumors and lymphomas.
  • Infections can be more prevalent in the population that is using Alefacept rather than in the control groups in the studies. These infections are also likely to be more severe and lead to more complications. Some of the ones that were seen included sepsis, abscesses, wound infections, pneumonia, and toxic shock syndrome.
  • Hypersensitivity problems are possible side effects, and, of these types of complications, there were seen both angioedema and urticaria in the patients. It is vital that any symptoms of an anaphylactic reaction are reported quickly and that swift medical attention is given to such cases.
  • Alefacept antibodies were seen to form in about 3% of the patients, and these antibodies do not have any known reason for being there as far as the efficiency of the drug is concerned. This could mean that they are going to have some long-term immunity, but this has not been fully researched on these grounds.
  • Hepatic Toxicity has been seen in quite a few people during their Alefacept treatment regimen. These issues occurred in the form of conditions such as fatty liver degeneration all the way to acute liver failure in some instances.
  • General side effects have also shown up with some frequency, but most of these can be handled with either minor medical intervention or through the body's natural processes. These include injection site reactions, pharyngitis, cough, dizziness, myalgias, chills, nausea, and pruritus. One of the most common times for these general side effects to occur was after the drug treatment was discontinued during trials, and these patients had a noticeable rate of lowered white blood cell counts, headaches, and nausea.

Dosage

In the Amevive form, there is a 15mg lyophilized powder that is used along with a supplied diluent in order to administer an intramuscular injection that is given at a rate of once per week for a 12-week regimen. There is also a lighter 7.5mg option that is available for those who need that for lymphocyte maintenance. This 7.5mg version is generally given through an IV rather than intramuscularly. During this time there should be a watch kept on the CD4+ T lymphocyte count of the patient being seen. There is also the chance that a subsequent 12-week regimen of alefacept is within the realm of possibility if there has already been a lapse of at least 12 weeks since the last time that one was given. It is also important to ensure that the CD4+ T count is normal before administering a second dose of the drug. Other medications should not be added to the drug during administration, and old injection sites should not be reused unless they have healed up appropriately.

0.75 mg/kg has been the highest level of alefacept given to a human, and it was administered through an IV. The occurring side effects were all relatively mild and included arthralgia, sinusitis, a headache, and chills. With this in mind, patients who have received too much of the drug (more than the recommended dose) should still be monitored so that it is recognized if any of their lymphocyte counts go askew.

Drug Interactions

One problem that can be a natural byproduct of such a drug is excessive immunosuppression as noted above in regards to the lymphocytes. For this reason, it is imperative that alefacept is not given to those patients who are already in the midst of some other type of immunosuppressive therapy. This might include the general phototherapy, or it might be that the patient is already taking a different type of immunosuppressive prescription medication.

CYP450 substrates are something that should be administered carefully after a patient has undergone an alefacept therapy protocol because of the fact that it can leave them with a normalized CYP450 enzyme level. The effect and drug concentration should be watched as appropriate in order to ensure that everything remains steady. Also, patients with HIV should not be given a treatment of alefacept because of its effect on the lymphocyte level that may cause the disease to progress faster than it otherwise would.

It is possible that those who have been given the traveler's diarrhea and cholera vaccine will have it inactivated by alefacept, and there is also the risk that the infection will take hold because of the mechanism of action. This increase in infection likelihood holds true for any live vaccines that are given at the same time that the alefacept is administered. Both of the versions of the typhoid vaccine that are recommended by the World Health Organization fall into this category and will most likely have their efficacy reduced. Adenovirus types 4 and 7 live as well as the hepatitis vaccine (all types), human papillomavirus vaccine, and the Haemophilus influenza type b vaccine will also all likely have a reduced effectiveness if given concomitantly with this medication.

Warnings

Cancers and serious infections can occur at a greater rate in the population that uses alefacept. It is also important that anyone who has a history of systemic malignancy or HIV avoid using this drug as part of their regimen. Usage in pregnant women has been considered generally acceptable despite the fact that there have been no real focused studies on alefacept in this regard. It is not recommended that breastfeeding is performed if the mother has recently been through a treatment regimen or if she is still in the midst of one during or after the course of a pregnancy term.

Storage

One the product is reconstituted it is necessary to administer it either immediately or else it might be stored in the vial for up to 4 hours while being kept at a temperature that is between 36 and 46 degrees Fahrenheit (2-8 degrees Celsius). The carton that it comes in (Amevive) should be used as the storage container in order to prevent light from interfering with its mechanism of action.

Summary

There are dual mechanisms at work in alefacept that give it its capabilities. To start with, the activation of both the CD4+ and CD8+ T cells is inhibited because of the fact that the drug interferes with CD2. Then, there is a programmed cell death known as apoptosis that takes place on those memory-effector varieties of T lymphocytes. The combined effect of these two mechanisms is what makes alefacept able to help with the improvement of patients who have moderate to severe psoriasis. An antibody protein and a protein are fused together so that the types of T cells that need reduction are limited in their growth ability.

Amevive did seem to be quite a viable prescription drug for some time until the company marketing it (Astellas Pharma US) decided to take it off of the market in 2011. There was never any traction in the European market due to it not getting approved, but there was quite a bit of progression in the United States as well as in Canada, Switzerland, Australia, and Israel. The side effects mentioned above did seem to interfere quite a bit, and then there were some contraindications in regards to live vaccines and such, but overall it seemed to be a promising drug. There may be others with a similar mechanism that make it to the market in the future to fill the gap.

Resources
Last Reviewed:
December 10, 2017
Last Updated:
April 04, 2018
Content Source: