Safety profile of biologics evolves, but long-term risk concerns remain

February 1, 2012

New safety profile data continues to emerge on biologics used in psoriasis. Among the findings: Today's biologics do not appear to increase serious infection risk; the drugs' short-term cancer risk profile is promising; but concerns remain about long-term cancer risk with all biologics and cardiovascular risk with interleukin-12/23, ustekinumab (Stelara, Janssen Biotech).

Key Points

"As more and more patients get put on various (biologic) treatments, we gain a better understanding of mature safety profiles," says Craig Leonardi, M.D., clinical professor of dermatology, Saint Louis University, St. Louis.

Especially with tumor necrosis factor-alpha (TNF-alpha) blockers, the evolution of safety data is comforting, he says. This is despite the Food and Drug Administration's Boxed Warning update in September 2011, adding risk of infection from bacterial pathogens legionella and listeria to the entire TNF-alpha blocker class.

TNF-alpha blockers, including Remicade (infliximab, Janssen Biotech), Enbrel (etanercept, Amgen/Pfizer) and Humira (adalimumab, Abbott), had mature safety profiles established in rheumatology before being used to treat psoriasis patients in dermatology, according to Dr. Leonardi.

"We've been rediscovering that safety profile now in our own psoriasis patients," he says.

Dr. Leonardi cites research by Joel M. Gelfand, M.D., M.S.C.E., assistant professor of dermatology, University of Pennsylvania, Philadelphia, which showed no increase in malignancy or serious infections for patients treated with biologics versus those treated with placebo.

"That was quite surprising and very good news," Dr. Leonardi says.

A limitation of the study, however, is that it was a short-term look at malignancy rates from biologic use (mean 17.8 weeks), which isn't long enough to fully address the cancer question, he says.

Dermatologists also have the benefit of years of TNF-alpha blocker safety data from rheumatoid arthritis registries. In general, that data of rheumatoid patients who are on standard-of-care versus standard-of-care plus TNF-alpha blockers show no increase in cancer, except for common skin cancers.

"So, for every malignancy issue that has been identified - breast, colon, lung cancer, renal cell carcinoma, even lymphoma and leukemia - there was no additional price to pay for being on the biologic drugs. That's nice data to have," he says. "The one issue that was increased was common skin cancers - basal and squamous cell carcinoma. Melanoma was trending toward statistical significance but had not yet achieved that."

Psoriasis registries

Whether the rheumatology data will translate to dermatology and psoriasis is a big question, Dr. Leonardi says. Psoriasis registries are up and running, but they are not as mature as in rheumatology. One of the more important psoriasis registries, according to Dr. Leonardi, is the Psoriasis Longitudinal Assessment and Registry (PSOLAR), a disease-specific registry sponsored by Janssen Biotech.

"What's neat about the PSOLAR registry is that it's not confined to just Remicade or Stelara (ustekinumab, Janssen Biotech) patients. We're allowed to put patients that are on any systemic medications, including other biologic drugs, into this registry. (Recently), we finally hit 10,000 patients in this registry," Dr. Leonardi says.