Treating moderate to severe psoriasis is difficult in the best of cases, but the most serious challenge I have encountered in practice is treating patients who were formerly treated with Raptiva.
In the way of background, Raptiva was a new biologic immunomodulating drug that was introduced by Genentech in 2003 for the treatment of moderate to severe psoriasis. Raptiva was a monoclonal antibody directed against a specific component of leucocyte function antigen-1 expressed on human T-lymphocytes. By blocking the interaction of LFA-1 with other molecules, T-cell activation and migration into psoriasis skin lesions was inhibited.
The early pivotal studies of Raptiva in the treatment of psoriasis indicated that it was very successful in clearing skin in about 40% of patients. Raptiva was a little more difficult to use in practice and somewhat less effective than later arriving competitors such as Enbrel, Humira, and Remicade. The latter drugs work by blocking a pro-inflammatory compound called tumor necrosis factor which is elevated in psoriasis patients. This advance caused most dermatologists to shy away from Raptiva in favor of the others, significantly reducing Raptiva’s market share as they began to dominate the marketplace.
Raptiva became a niche drug. First, only very experienced clinicians with a high volume of psoriasis patients would use it. After a while, it seemed that only patients who had failed to respond well to tumor necrosis factor inhibitors became candidates for Raptiva. The other niches were patients with psoriasis of the palms and soles, especially the pustular type, which can be quite disabling, and overweight patients, because the dose of Raptiva was based on the weight of the patient.
It is understood that all of the biologic drugs improve psoriasis by inhibiting a portion of the immune system involved in the inflammatory process which is also required for fighting off and preventing infection and cancer. For this reason, I tell patients who are about to receive any of these drugs that there is an increased risk of infection, especially reactivation of dormant tuberculosis, and certain types of cancer, especially lymphoma. These warnings are also clearly pointed out in the package insert material mandated by the FDA. The infections and lymphomas have been more prevalent in patients with more serious illnesses such as rheumatoid arthritis and Crohn’s disease which are also often treated with other immunosuppressive drugs.
Thus, in 2008 we were surprised to learn of the first cases of progessive multifocal leukoencephalopathy (PML) occurring in otherwise healthy patients with psoriasis who were not also receiving other immunosuppressive drugs. PML is viral infection of the central nervous system caused by the JC-virus which lays dormant in most people. Early on, some of the neurologic symptoms are like multiple sclerosis (MS), but PML is rapidly progressive, not treatable and may be fatal. By the time four cases of PML had been reported in psoriasis patients on Raptiva, in rapid succession, the European Union removed it from the market, the FDA required stronger package insert warning language about PML and other infections, and the manufacturer Genentech voluntarily withdrew the drug . At least three of the affected patients are known to have died. Curiously, another monoclonal antibody called Tysabri which has a different mechanism of action than Raptiva, used in the treatment of MS, was associated with 2 cases of PML , one fatal. Tysabri was withdrawn in 2005 and reapproved by the FDA in 2006.
In the first few months of 2009, I either called or saw all of my patients on Raptiva and asked them if they wanted to stop Raptiva immediately given the newly discovered risk factor, or did they want to continue it until the last vial of stock would be available in June. What would you do? As a doctor, I want to first do no harm and preferred them all to stop immediately. However, you can only answer the question honestly if you have severe disabling psoriasis and have been clear for years on Raptiva alone. Most of my patients had already been through and either failed or had side effects from narrow band UVB phototherapy, hand and foot PUVA, methotrexate, Soriatane, Enbrel, and/or Humira. Some had painful pustular psoriasis of the palms and soles which made them unable to work with their hands or to walk normally. Their psoriasis had been totally gone for years when nothing else had worked. They didn’t even have to think about something that had been the focus of their lives except to give themselves that one little shot once per week. I believe they all used Raptiva to the very last vial, and some tapered it off by dose or by frequency in attempts to both reduce risk while staying clear. No one brought in any unused Raptiva for me to destroy or return to Genentech. On my next blog, I will discuss what happened next and how I handled the cases, but happily, none of my patients developed PML.
