COPENHAGEN – Ixekizumab showed no hint of an increased malignancy risk of any sort in 4,208 patients with moderate to severe psoriasis who had 6,480 patient-years of exposure to the investigational interleukin-17A inhibitor in seven clinical trials.
“Patients were studied for an average of 18 months on ixekizumab. You may say that’s not enough time to assess the true risk for malignancy, and I would say you’re probably right. But 18 months isn’t shabby. From such an exposure, we can get some sense of the malignancy risk with this drug,” Dr. Bruce E. Strober asserted at the annual congress of the European Academy of Dermatology and Venereology.
That’s a key issue whenever a dermatologist prescribes a potent immune-altering anti-inflammatory medication for an indefinite period of time, he added.
In the randomized trials in which more than 2,300 patients who received 80 mg of ixekizumab every 2 or 4 weeks were compared with 739 patients assigned to etanercept (Enbrel) and 791 on placebo, malignancy rates were similarly low, at 0.1-0.3 cases per 100 patient-years across all four treatment arms, reported Dr. Strober, chair of the department of dermatology at the University of Connecticut, Farmington.
Moreover, in the long-term maintenance studies featuring 60 months of follow-up, the risks of both nonmelanoma skin cancer and other types of cancer were similarly low in patients randomized to ixekizumab at 80 mg every 2 weeks and those dosed every 4 weeks. That’s reassuring, because if a drug causes cancer one would expect to see that the more of the drug given, the higher the malignancy rate.
“You really don’t see any kind of a pattern or any difference between the various compared groups, including patients on etanercept, a drug that all of us feel very comfortable using in patients with psoriasis,” the dermatologist observed.
It’s thought that psoriasis patients have a higher background risk of malignancy than the general population due to the nature of the chronic disease, which involves immune dysregulation and chronic inflammation. In the studies to date, however, the malignancy risk in ixekizumab-treated patients is similar to those on placebo or etanercept.
“In my opinion, it’s comforting that the malignancy rates of the currently approved biologic agents for psoriasis are low and – one could argue – not above that which you would expect for the population of patients we’re treating. So I’ve always felt that monotherapy – and that’s an important point, not combination therapy with other immunosuppressive drugs – offers very little risk of de novo malignancy with the currently approved biologics,” Dr. Strober said.
Lumping together the results of the seven studies in his analysis, the incidence of squamous cell carcinoma was 0.1 cases per 100 patient-years of ixekizumab exposure, the risk of basal cell carcinoma was 0.3 cases per 100 patient-years, and the risk of malignancies other than nonmelanoma skin cancer was 0.5 per 100 patient-years of exposure to ixekizumab.
“That’s basically in line with every other biologic that I’ve examined with regard to malignancy rates: about 1 in 200 patients treated for 1 year gets a nonmelanoma skin cancer of some nature if you look at all data sources, including long-term registries and clinical trials. So it appears that this drug falls right in line with the other biologics in terms of rates of the more serious cancers, at least over the time period studied,” Dr. Strober commented.
He offered a caveat, however: “What will happen in patients given combination therapy with other immunosuppressive drugs? Or special populations, such as patients at higher risk for malignancy, be it skin cancer or other types of cancer? Or – and here’s the question we often have the most difficulty answering – what about people with a prior history of malignancy? What would be their risk of malignancy in being placed on a drug of this nature? Only time and really good registry data will allow us to answer these questions.”
Dr. Strober is a consultant to Eli Lilly, which sponsored the seven ixekizumab studies, as well as to numerous other pharmaceutical companies.
bjancin@frontlinemedcom.com
