I do believe Dr. Levine gives an overly optimistic view of the benefits of these four drugs over biologics.
Dr. Levine's main thrust of his current commentary relates to "risks, benefits and costs of therapy," as well as his concern of "pushing the healthcare system over the cliff of affordability." He then chooses to discuss four systemic "pre-biologic therapies," ie. methotrexate, cyclosporine, acitretin and thioguanine, giving predominantly positive views on all, while briefly touching on "rare or unusual side effects" relating to these drugs.
Having published data on three liver transplants from our institution due to excessive methotrexate use, as well as having sat anxiously with a patient's family for a weekend after hepatic shutdown from 6-thioguanine, and being unable to utilize acitretin for females of child-bearing potential (significant proportion of our patient population), I do believe Dr. Levine gives an overly optimistic view of the benefits of these four drugs over biologics.
I do believe Dr. Levine belittles our psoriatic population by stating that there is "no compelling reason to choose these extraordinarily expensive and relatively untested medications." TNF agents, for instance, have been used in more than half a million patients with disorders such as rheumatoid arthritis and Crohn's disease, which inherently have more co-morbidities than our psoriasis population. Thus, why should our psoriasis population, with quality of life issues equal to, if not exceeding, these two aforementioned diseases, also not be eligible for the "extraordinarily expensive" agents? Psoriasis patients deserve equal access to medications that are safe for the long-term.
My personal use of the three traditional agents (thioguanine excepted) has continued unabated since the biologics have been introduced. Certainly, they should be considered as first line systemic agents. However, there are many patients in whom I cannot use methotrexate, cyclosporine or acitretin, ie. patients with hepatitis C, patients with hypertension, patients considering pregnancies, etc. In addition, cyclosporine is only approved for one year of therapy. What do I do then if the patient is unwilling to forsake alcohol and is a patient of child-bearing potential? Do I "push the envelope" with methotrexate, recognizing also that a significant proportion of patients on methotrexate feel "washed out" for 24 to 48 hours after their weekly dose? It is incumbent upon psoriasis specialists to create specific paradigms for treatment for our patient population with moderate to severe psoriasis requiring systemic therapy for the long term. Just as the mode of administration and dosage of methotrexate went through a great deal of change for the first five to 10 years of its existence in the 1970's, so we will learn how best to use biologics in the future, both from an efficacy, safety and cost perspective.
To belittle biologics because of their expense belittles our patients who are deserving of expensive medications when appropriate. The fact that we, as dermatologists, now have a full range of treatments available to us, including traditional systemics and biologics, puts us on a par with our colleagues in rheumatology and gastroenterology. Why should we settle for being second-rate physicians?! Medical dermatology is under siege already. Abandoning biologics along the lines of what Dr. Levine proposes will further diminish its importance.
I sincerely appreciate the opportunity of responding to Dr. Levine, a colleague and close friend, for whom I have great respect but opposing views in the area of safe long-term effective therapy for our psoriasis population.
Alan Menter, M.D., President, International Psoriasis Council.