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Biologics are revolutionizing how psoriasis is treated, and what psoriasis patients are coming to expect from their psoriasis treatments. Biologics are generated from living things--human and/or animal proteins. Anti-psoriasis biologics have been developed based on current understanding of the abnormal immune system responses that contribute to the disease. As such, they are designed to ‘target’ specific parts of the immune system. The goal is to weaken or immobilize those features of the immune system that are triggering psoriasis without the adverse side effects that can come from broadly weakening the immune system.
The current biologics are:
alefacept (brand name Amevive)
efalizumab (Raptiva)
infliximab (Remicade)
etanercept (Enbrel)
adalimumab (Humira)
Biologics for psoriasis fall into two categories: Amevive and Raptiva inhibit T cells, the immune cells that congregate in psoriasis plaques and trigger inflammation. Remicade, Enbrel and Humira inactivate Tumor Necrosis Factor alpha (TNF-alpha), an inflammation-promoting substance produced by activated T cells in psoriasis patients. [Note: several companies that market psoriasis biologics have provided unrestricted, no-strings-attached grants to Psoriasis Cure Now.]
Generally speaking, these biologics are FDA approved for adults with moderate to severe plaque psoriasis (Humira has an application before the FDA for psoriasis that is likely to be approved later in 2007), and Enbrel, Humira and Remicade are also approved for psoriatic arthritis.  No biologics are currently approved for psoriasis in minors/children, although some of them are approved for pediatric use for other diseases.
These biologic agents are proving to be highly effective at treating psoriasis, including for many people with severe disease, and they are delivering these results with minimal side effects in most cases. Simply put, many people take their biologic, see major improvement in their psoriasis, and experience no side-effects. While the U.S. Food and Drug Administration looks at what percentage of patients achieve a 75% improvement after 12 weeks of treatment, many patients who achieve “just” a 50% improvement are thrilled with the results; and some patients even see 90% improvement with each of these biologics.
But they are not without risks. In rare cases, their side effects can be serious, and there have even been fatalities (although as you will see below under Drawbacks, if a patient does *not* have TB, heart disease, hepatitis B, or other serious preexisting conditions, the rare side effects are even more unlikely to occur). And given that the oldest of these, infliximab, received FDA approval in 1998, their long-term safety record is still being established. There is concern, and considerable debate, about the potential for increasing cancer risk by impacting the immune system with a biologic treatment. But we just don’t know yet if this risk will prove true and if it does, how much risk it will add. Finally, biologics are very expensive; few patients can afford them unless they are covered by insurance, which varies by insurer. Click here for more on insurance coverage.
But for those with significant psoriasis, biologics offer powerful new options and the possibility of dramatic improvements in physical--and emotional--well-being. Click here to listen to a free podcast about biologics for psoriasis and here to read a biologics success story.
Amevive (alefacept)
In 2003, Amevive became the first biologic to get the green light from the FDA for treatment of plaque psoriasis. Amevive is marketed by Astellas Pharma US. In clinical trials, after 12 weeks, about one in five patients met the primary benchmark for improvement set by the FDA for psoriasis treatments; that is, a 75% improvement in psoriasis skin symptoms (called PASI 75). After a second course of treatment, that figure rose to about one in three patients.
How is it administered? Amevive is administered in a physician’s office by injection into the muscle once a week for 12 weeks. After a 12-week rest period, patients can receive a second 12-week course of therapy.
Advantages The anti-psoriasis effects of alefacept can last even months after treatment ends, so for those who like the idea of taking treatment “holidays,” Amevive may offer a way to take significant breaks between treatments regimens.
Drawbacks Alefacept works against psoriasis, in part, by reducing the number of T cells in the body; however, if T cells levels drop too low, the body’s ability to fight infection can be seriously impaired. Therefore, doctors recommend regular monitoring of T cell levels in patients receiving alefacept (with a simple blood test every two weeks during treatment), and discontinuation of the medication if they go below a healthy level.
Alefacept is relatively new, and its patient population is limited, so it could have as-yet-undiscovered, serious side effects.
How does it work? Amevive is a two-part molecule consisting of a portion of the human leukocyte function antigen-3 (LFA-3, a molecule found on the surface of T cells) joined to a portion of IgG1 (a human antibody). Amevive is one of the two biologics (the other being Raptiva) that cripples T cells. Normally, LFA-3 on the surface of T cells binds to a molecule called CD2, and this interaction promotes activation and survival of the T cell. Amevive (alefacept), essentially a “free floating” form of LFA-3, can bind to CD2 instead and prevent CD2 from finding T cell associated LFA-3. As a result, T cells are less active and many die.
Raptiva (efalizumab)
Raptiva, marketed by Genentech, received FDA approval for the treatment of plaque psoriasis in 2003. In clinical trials, roughly three in 10 patients achieved a 75% reduction in psoriasis severity (PASI 75) after 12 weeks. In addition, about half of patients who achieve improvement from 50%-74% after 12 weeks, will reach PASI 75 if treatment continues. And an extended study showed Raptiva continued working for most patients for the three years of the trial (far longer than the 12 weeks reviewed by the FDA).
How is it administered? Raptiva is self-administered by injection under the skin once a week. Raptiva requires continuous treatment to keep psoriasis in check.
Advantages Raptiva can help even people with severe psoriasis achieve dramatic clearing of their psoriasis with a simple, weekly self-injection under the skin. Raptiva has also been clinically shown to be effective against hand and foot psoriasis, particularly challenging types of psoriasis. Click here to listen to a free podcast about hand and foot psoriasis and Raptiva’s use for this type of psoriasis.
Drawbacks Some patients experience potentially serious side-effects, including: a loss of platelets (thrombocytopenia), blood cells essential for clotting; anemia; and a worsening or new forms of psoriasis or arthritis during treatment or after ending treatment. Each of these was seen in less than one percent of those enrolled in the clinical trials. To avoid a “rebound,” or worsening of psoriasis after stopping treatment, it is recommended that a patient move to a new treatment as Raptiva is discontinued.
Patients can also get fevers and chills following the first several injections.
How does it work? Raptiva (efalizumab) is an antibody that binds to leukocyte function antigen-1 (LFA-1), a molecule found on the surface of immune cells, including T cells. Like Amevive, it reduces psoriasis symptoms by inhibiting T cells, specifically by preventing T cells from binding to other cells in the body. During the initial stages of T cell activation, LFA-1 on the T cell needs to contact a molecule on the surface of other immune cells called intercellular adhesion molecule-1 (ICAM-1). Similarly, in order to leave the bloodstream and enter the skin, T cells need to bind via LFA-1 to ICAM-1 located on blood vessel walls. By binding to LFA-1 on T cells, efalizumab interrupts both of these interactions, reducing T cell activity and blocking the ability of T cells to congregate in the skin at the sites of psoriasis plaques.
Remicade (infliximab)
Remicade has proven to be very effective against several inflammatory diseases. The oldest of the biologics currently being used to treat psoriasis, Remicade first received FDA approval in 1998 for the treatment of Crohn’s Disease. Subsequently, it received approval for use in patients with rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and in 2006, severe plaque psoriasis. It is marketed by Centocor. Remicade is very effective for psoriasis, with more than three-fourths of patients achieving 75% reduction in psoriasis severity (PASI 75) after 10 weeks, including nearly 60% of patients who achieved a 90% improvement. Click here for a free podcast about Remicade for psoriasis.
How is it administered? Remicade is administered by IV (intravenous infusion) in a physician’s office; receipt of a single dose takes 2-4 hours. Patients usually receive the first three doses within 10 weeks and then a dose every eight weeks.
Advantages Remicade is highly and rapidly effective, and is approved specifically for severe psoriasis. Once the initial doses are administered, maintenance therapy is just once every eight weeks, and patients typically read or watch TV during the infusions.
With more than 800,000 patients treated with Remicade worldwide for various diseases, the medical community has a strong understanding of the risks of Remicade use. (Of course, as with all biologics [and most other treatments], we don’t know if new risks will emerge after 20/30/40 years.)
Drawbacks A small minority of patients—less than 1%—experiences a life-threatening allergic reaction (anaphylaxis) during infliximab administration. About 20% of patients experience a milder reaction.
There are several very rare, but serious, side effects that occur in patients taking infliximab, and there have been fatalities. Some patients have had serious infections (including TB, tuberculosis) A few patients have developed a reversible lupus-like autoimmune disease. Others have developed a demyelinating disease of the central nervous system, similar to multiple sclerosis (MS). Still others experienced a drop in white blood cell levels. The risk of lymphoma and possibly other cancers appears to be increased in patients taking Remicade and other TNF-alpha inhibitors. Remicade can make congestive heart failure worse and has in rare cases caused liver problems. It can reactivate the hepatitis B virus in those who have had it.
You should not receive a live vaccine while taking Remicade.
How does it work? Remicade (infliximab) is a combination human and mouse antibody that binds to and inactivates TNF-alpha, a pro-inflammatory substance released by activated T cells in psoriasis plaques. An excess of TNF-alpha can lead to psoriasis symptoms. Remicade reduces the amount of TNF-alpha in the body. Enbrel and Humira work by a similar mechanism.
Enbrel (etanercept)
Enbrel is currently used to treat plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and juvenile rheumatoid arthritis. Marketed by Amgen and Wyeth, it received its first FDA approval in 1998. In clinical trials, one-half of patients experienced a 75% reduction in psoriasis severity (PASI 75) after 12 weeks of twice weekly treatments. In addition, about one-third of the patients who did not achieve 75% improvement by week 12 did so by week 24. Also, one-fifth of patients achieved a 90% improvement by week 12.
How is it administered? Enbrel is administered by self-injection under the skin twice weekly for 12 weeks, and once weekly thereafter (although some patients are continued on the twice-weekly dose).
Advantages Enbrel is considered to have a favorable balance between benefit and risk, and brings dramatic improvement to many psoriasis patients safely. Like Remicade, it is approaching a decade since its first FDA approval, and with more than 450,000 patients treated worldwide for various diseases, there is a significant track record for the medical community to assess its potential risks.
Drawbacks Many of the rare but serious side effects associated with Remicade have also occurred very rarely in patients taking Enbrel. These include: serious infections (including TB), central nervous system demyelinating disorders (like MS), lupus-like autoimmune disease, worsening of congestive heart failure, decreased white blood cell count, and cancer. In most cases, these problems have been so rare that is has not been possible to conclusively link them to Enbrel use.
How does it work? Enbrel (etanercept) consists of two copies of part of the TNF-alpha receptor, the natural binding site for TNF-alpha, joined to a portion of a human antibody. The TNF-alpha receptor portion of Enbrel binds and neutralizes TNF-alpha, reducing the excess inflammatory TNF-alpha found in psoriasis patients.
Humira (adalimumab)
Humira first won FDA approval in 2002 and is currently used to treat psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis and Crohn’s disease. Humira is very effective, with more than two-thirds of patients in clinical trials experiencing a 75% reduction in psoriasis severity (PASI 75) after 16 weeks of treatment, including about 40% of patients who achieved a 90% reduction in psoriasis severity.
How is it administered? Humira is administered by self-injection under the skin, typically once every two weeks.
Advantages Humira is highly effective, with convenient self-dosing every other week. In addition, it is a fully human protein, which may make it less allergenic than biologics that are partially derived from animals.
Drawbacks Humira appears to have the same safety concerns as the other two TNF-alpha inhibitors, Remicade and Enbrel. Potential serious side effects of Humira include severe infection, cancer, demyelinating disease, autoimmune disease, worsening of congestive heart failure, and blood cell disorders. There have been several cases of reactivated tuberculosis (TB) in patients taking Humira. While not used as long or as often as Enbrel or Remicade, its 180,000 patients worldwide for a variety of diseases is a significant figure that helps the medical community’s ability to assess Humira’s risks.
How does it work? Humira (adalimumab) is a human antibody that binds to and inactivates TNF-alpha. Like Remicade and Enbrel, it reduces TNF-alpha levels in the body, which leads to improvement in psoriasis symptoms.
Conclusion
Even as these biologics transform many lives, others continue to suffer with psoriasis. Some patients cannot access these treatment due to insurance/cost issues, some are precluded from using them due to preexisting conditions (TB, HIV, etc.), some are concerned about side effects or long term uncertainties, and some are simply not aware of these new treatments. For still others, their first try with a biologic does not work. (After all, no biologic works in 100% of cases.)
This is leading physicians to consider what to do in cases when a biologic does not appear to be working. In some instances, the answer is for a patient to have patience, as clinical response has been shown to continue improving for some patients after 12 weeks, or 16, or even 24. Other psoriasis patients will fail with one biologic but succeed with another (or even a third), probably because the mechanism of action for each is slightly different.
And yet it also appears clear that the current landscape of products will not work for everyone.  Some physicians are willing to experiment with medications approved for other diseases to try to help a desperate psoriasis patient who is not having an adequate response to treatments approved for psoriasis. Known as “off-label” use, it typically involves trying a patient on medications approved for other immune diseases that are known to respond to similar treatments. For example, several treatments are used not just for psoriasis but for rheumatoid arthritis and Crohn’s disease. Even treatments for diabetes and MS are considered, given the immune system roots of these diseases. For a while, it was thought that the diabetes treatment Avandia (rosiglitazone maleate) might work for psoriasis patients, but major, Phase Three studies disproved that theory. Orencia (abatacept), recently approved for rheumatoid arthritis, was shown several years ago in a very small study to improve psoriasis symptoms. (We spoke in support of FDA approval of Orencia for this reason.) As treatments improve for RA, Crohn’s and other immune diseases, options for psoriasis patients may continue to expand as well. And the psoriasis treatment pipeline is brimming with additional potential options. Many of them will not ultimately prove effective as they wind their way through the rigors of clinical trials, but some of them are indeed likely to be added to the treatment arsenal in the years ahead. You can learn more about the psoriasis treatment pipeline here.
But until every psoriasis patient has found safe and effective relief, it is essential that research on psoriasis continue. Even those of us finding relief with a current treatment must stay committed to help the others of us still searching for relief. Will you take two minutes right now to write your lawmakers and ask for expanded psoriasis research?
The biologics revolution is helping many psoriasis patients with moderate to severe disease reclaim a rich quality of life. Hats off to the biotech, pharmaceutical, scientific and medical communities for making these treatments possible.
Selected References:
Boehncke, W-H et al. “Biologic Therapies for Psoriasis. A Systematic Review.” Journal of Rheumatology. 2006 Jul;33(7):1447-51.
Nelson, AA et al. “New treatments for psoriasis: Which biologic is best?” Journal of Dermatological Treatment. 2006;17(2):96-107.
Information on drug approval from the Food and Drug Administration’s website.
Here are links to the biologics websites:
Remicade (infliximab)
Raptiva (efalizumab)
Humira (adalimumab)
Enbrel (etanercept)
Amevive (alefacept)
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