Once considered a novelty in psoriasis therapy, biologic agents now play a more prominent role in the treatment of moderate to severe psoriasis. The benefits of biologic agents are seen daily, as a majority of treated patients have clear or almost clear skin for many years. As strong efficacy data have accumulated and use of biologics has becomes more widespread, safety concerns have persisted, in many respects due to a lack of long-term data. While this limitation would uniformly be the case for most new drug therapies, clinicians have been perhaps more sensitive to the lack of long-term data for biologic therapies. For one, the entire therapeutic class is relatively new to dermatology.
Furthermore, withdrawal of Raptiva (efalizumab, Genentech) from the market last year increased interest in safety and raised concerns, especially among dermatologists who have not used these agents and likely would not consider them as appropriate for patients with moderate to severe psoriasis.
Despite these concerns, it is important to remember that several biologic agents have been studied and prescribed for many years in medical specialties other than dermatology.
New Safety Data
We may tend to think of biologic therapies as being new, but how long must a drug be used before it's no longer considered new? Etanercept (Enbrel, Amgen) was first trialed on humans in 1992 and subsequently has received FDA approval for rheumatoid arthritis, psoriatic arthritis, and then psoriasis, and has been used in over 800,000 people for over two million patient years. Adalimumab (Humira, Abbott) has been tested in over 400,000 humans since 1997. Given that both of these agents have been on the market for some time, recent studies have been able to assess the long-term safety of etanercept and adalimumab.
Adalimumab Data. In one study, researchers evaluated data from 36 global trials for patients with rheumatoid arthritis (RA), juvenile RA, Crohn's disease, and psoriasis receiving adalimumab— in some cases for over one year.1 In total, 19,00 patients were treated in these trials. The most common adverse events seen in these trials were infections, which were most common in the RA and Crohn's patients. Among psoriasis patients, the frequency of infection was comparable to that of the general population, with very few cases of opportunistic infections or demyelinating disease. In addition, the risk of malignancy was not any greater in the treated patients versus the general population.
The risk of tuberculosis was also observed to be low for all patients receiving adalimumab. However, there was a slight increase in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) observed in both the psoriasis and Crohn's disease groups. In addition, the number of lymphomas was proportionally higher than those of the general population.
It's worth noting, however, that patients with severe RA already have a 70-fold increased risk of lymphoma.
Finally, there were no more deaths reported (proportionally) among treated patients than in the general population.
Etanercept Data. Another new study, this one evaluating the long-term safety of etanercept, offers firm support for the drug's current strong safety profile. In the study, 912 patients received etanercept for 12 weeks, totaling 1,056 patient years.2 The drug was found to be well-tolerated, with no difference seen in terms of adverse events in patients who received it once a week versus twice a week. For those patients who received treatment for up to a year, some infections such as pneumonia and cellulitis were observed.
There were no cases of TB reported, nor was there an increase in demyelinating diseases. There was one case of melanoma reported, however, it occurred in a patient who previously had been treated with extensive PUVA therapy. Overall, malignancies among treated patients were proportionally less than are seen in the general population.
Based on these recent data, it does not appear that there have been any new safety signals emerging in the post-clinical trial area than were observed in the clinical trial data. Moreover, these studies assessing the long-term safety of etanercept and adalimumab provide further evidence that these established biologic agents are not just efficacious, but safe and appropriate for the treatment of patients with moderate to severe psoriasis.
Dr. Bagel is on the speaker's bureau for Abbott Labs, Amgen, Centocor, Galderma and Leo Pharma.