Magazine article Clinical Psychiatry News

Hype and Hope of Psoriasis Biologics Examined

Magazine article Clinical Psychiatry News

Hype and Hope of Psoriasis Biologics Examined

Article excerpt

NEW YORK -- Collectively hailed as the biggest breakthrough for psoriasis therapy in decades, infliximab, etanercept, alefacept, and the other "targeted biologics" seem poised to revolutionize how dermatologists treat moderate to severe psoriasis.

Alongside the well-warranted excitement, however, psoriasis experts at the Ninth International Psoriasis Symposium also voiced their concerns about the costs of the new medications, their potential for adverse effects, and their ability to be combined with one another or with older drugs.

Currently, three of the new biologics have been approved by the Food and Drug Administration: etanercept (Enbrel), for psoriatic arthritis and rheumatoid arthritis (RA) in both adults and children; infliximab (Remicade), approved for Crohn's disease and RA; and most recently, alefacept (Amevive), which is the only one officially approved for psoriasis. More approvals are expected in the next few years.

The highly specific nature of the biologics is supposed to reduce the risk of toxicity and adverse effects associated with older, systemic immunosuppressants such as methotrexate and cyclosporine, Dr. Menno de Rie said at the meeting, sponsored by the Skin Disease Education Foundation. The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

Nevertheless, one should not be lulled into thinking that targeted biologics are trouble free. "TNF [tumor necrosis factor] inhibitors do have adverse effects," said Dr. de Rie, of the University of Amsterdam.

The major adverse events include immune reactions at or around the site or injection, autoimmune phenomena, and infections, including tuberculosis, granulomas, and lymphomas. The latter is particularly disturbing.

Though the absolute numbers are still small, Dr. de Rie noted that the etanercept clinical trials show a two- to threefold increase in lymphoma among patients on active treatment, compared with placebo. In the infliximab trials, the increase was six-to ninefold. For adalimumab, a drug that has not yet hit the psoriasis market, there was a fivefold increase.

In terms of treatment-related infections, Dr. de Rie explained that "TNF-[alpha] is crucial for killing bacteria. Macrophages produce TNF-[alpha], and it is also important for natural killer cells. If you block TNF-[alpha], it could have negative effects, which is a cause for concern."

On the basis of data submitted to the FDA, there is a treatment-associated tuberculosis rate of 82 per 170,000 treated patients for infliximab, and of 11 per 104,000 for etanercept. While the latter is consistent with general background incidence rates, the former is somewhat higher.

In general, the side-effect profiles of the biologics are quite acceptable, given the devastating day-to-day impact of severe psoriasis. But at the same time, it is important to keep potential side effects in mind and to monitor patients closely.

When it comes to rapidly clearing severe psoriasis, the biologics deliver "socko" efficacy, as Dr. Alice Gottlieb likes to say.

"The future holds far better things than we have now, but ... for those of use who actually use the targeted biologics, they really have an impact on real peoples' lives. We can clear psoriasis," said Dr. Gottlieb, chair of clinical pharmacology at Robert Wood Johnson Medical School, New Brunswick, N.J.

The clinical trials seem to bear out her assertion. In one phase II trial, 59% of patients with moderate to severe psoriasis treated with 50 mg etanercept twice weekly for 24 weeks had 75% reductions in Psoriasis Area and Severity Index (PASI) scores. The "PASI 75" has been the primary therapeutic end point in all of the major biologics' trials, and 49% of patients on the 50-mg dose reached this milestone within 12 weeks. At 25 mg, etanercept was not as effective, with only 34% of patients reaching PASI 75. In the placebo group, only 4% reached PASI 75 at 24 weeks. …

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