– Drugs improve the treatment of psoriasis.
During biblical times people with psoriasis were treated by society the same as lepers were and lived as outcasts of society. Today, some people who have lived with scaling rashes for years get their smooth, soft skin back almost as if by magic. However, a lot of research remains to be conducted before there is a drug to suit everybody.
Different phenotypes with different pathogenetic pathways
The red, scaling spots often appear relatively early in life, half of those who suffer psoriasis having a debut before the age of 25. Sometimes tonsillitis is the trigger. The rashes often appear on elbows, knees and in the scalp but in some individuals may spread all over the body.
“Many people have to live with this throughout their whole life. In our current culture, this can entail considerable stress” says Mona Ståhle, Professor of Dermatology and Venereology, and one of the doctors who have their laboratory located at CMM.
Some people do not want to put themselves and their lesions on view. They never wear shorts or short-sleeved shirts, and prefer to go swimming when no one is looking, even though the sun’s rays would do their skin a lot of good.
A quarter of a million people, around 3% of Sweden’s population, have psoriasis. For most of these it is sufficient to daub their patches with a vitamin D-enriched cream. But 10-15 % have such a widespread disease that they have to be treated with oral medicine. In recent years, new treatments have revolutionized life for some people who have severe psoriasis. After years of ointments, light therapy and small doses of chemotherapy, the red, scaling skin has finally healed completely.
“There is no lasting damage to the skin from psoriasis. If you can reduce the inflammation the skin can revert back to completely normal again. For many people, this has changed their life” relates Mona Ståhle.
One important treatment strategy is the use of of the so-called ‘TNF-alpha blockers’, which were actually developed for people with rheumatoid arthritis. Those who have not received clinical benefit by for example TNF-alpha blockers have been able to be treated with another drug, Raptiva.
“It had an incredibly positive effect on around 20 % of all patients with severe psoriasis” says Mona Ståhle.
But last spring the pharmaceutical company that developed Raptiva decided to stop producing it. Four out of the 70 000 patients who were given the preparation world-wide had by that time died from a brain infection called PLM, progressive multifocal leukoencephalopathy. This virus exists in the brain of 70-80 % of all people, but is normally kept in check by the immune system. When Raptiva suppresses the immune system, it gives the virus a chance to flourish.
“That was a real setback” comments Mona Ståhle.
The clinical remission that some patients experienced is now over, and they see their patches reappear. But there is hope. At about the same time that Raptiva was recalled, the Medical Products Agency decided to let another preparation, Stelara, be included in the pharmaceutical benefit. This is especially developed for psoriasis and inhibits two of the substances which activate the immune system in the disease, interleukin-12 and interleukin-23.
“Stelara has had a very positive effect in trials. Around 80 % are helped” Mona Ståhle states.
Those who get these new, so-called ‘biological drugs’ are now carefully monitored through special registries to uncover potentially serious side-effects in time.
“These days, we supervise medication much better than we used to. It is important that we catch early signals of side-effects” Mona Ståhle explains.
Slowing down psoriasis is not merely a cosmetic issue, but also important for the patients’ future. Epidemiological studies have revealed that severe psoriasis can increase the risk of cardiovascular diseases by about four times.
“We have realised that psoriasis is a more serious disease than we had previously believed. It is not a good thing to go around with a chronic inflammation” relates Mona Ståhle.
People with psoriasis are also at greater risk of becoming overweight, although scientists do not understand why. Mona Ståhle views the new drugs of recent years as a start of a new era in which more knowledge will lead to ever more effective drugs with fewer side-effects. When the scientists learn more about what sets different forms of psoriasis apart, they will also be able to provide more specific treatment. Today, a patient may need to try many different treatments before one takes effect.
“The more we learn about the disease, the better we understand which molecules are worth blocking” she says.
An important part of her research is studying skin cells and how they regenerate. In psoriasis the skin cells divide at an extremely rapid pace, which creates the scales. In a study which is unique in the world, her research team monitors the skin at a molecular level in young people who develop psoriasis following a tonsillitis infection. They chart the cells from the first eruption and see what happens when the patches are treated and when they recur again. Parallel to this, they also study the patients’ genes in order to identify genetic risk factors, which make it possible to differentiate between different types of psoriasis. But it is not all about molecules, genes and drugs. Stress and mental illness can also spur the disease on.
“We have started focusing more and more on caring for the whole patient and their lifestyle. If we can help the whole person feel better, they can also respond better to treatment” concludes Mona Ståhle.
According to scientific studies, people with psoriasis feel that it can be difficult to go to public baths, for example, because they feel singled out. Their sex life can also be affected, especially in younger people. Today’s pursuit of the perfect appearance simply makes the disease harder to live with. New and better drugs could therefore make life easier for many people.
Psoriasis is caused by a disturbance to the immune system. The individual experiences an inflammation of the skin which leads to red, scaling rashes.
TNF-alpha blockers are drugs which impede TNF-alpha, a substance which occurs naturally in the body and speeds up the immune system. People with psoriasis often have too much TNF-alpha in their body.
Raptiva is a drug which was recently recalled. It blocks the molecule LFA-1 present on lymphocytes and thereby reduces the infiltration of lymphocytes into the skin. Raptiva had a positive effect in 30-40 % of all patients suffering from severe psoriasis. But in rare cases, the treatment leads to patients developing progressive multifocal leukoencephalopathy, PML, a fatal, opportunistic infection which can occur in individuals with a compromised immune system.
Stelara is a completely new drug. It blocks interleukin-12 and interleukin-23, which are important activators in the immune system. Current research indicates that interleukin-23 is an important molecule for skin inflammation in psoriasis.
Text: Ann Fernholm