Brodalumab shows low rate of malignancy in psoriasis treatment

Brodalumab, an anti-interleukin-17 receptor A monoclonal antibody used to treat adults with moderate to severe plaque psoriasis, was shown to have low rates of malignancy, according to findings published in American Journal of Clinical Dermatology.

Data pooled from a 12-week, open-label phase 2 study and three 52-week, randomized, multicenter phase 3 studies (AMAGINE-1, AMAGINE-2 and AMAGINE-3) looked at the rate of malignancy events as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY).

Benign, malignant and unspecified malignancy events were reviewed blind by study staff. Confirmed malignancies were categorized as adjudicated malignancies, which were then further categorized as Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies or nonmelanoma skin cancers (NMSCs).

Each study included adults older than 18 years with plaque psoriasis and Psoriasis Area and Severity Index (PASI) score greater than 12.

Baseline characteristics were similar among patients across the initial 12-week period; 70% of patients were men, 90% were white and 57% were 40 to 65 years old. The mean duration of psoriasis was around 18.5 years, 21% had psoriatic arthritis, the mean PASI score was 20.1, and 2% to 3% of patients reported a history of malignancy.

The studies were placebo controlled for the first 12 weeks, but AMAGINE-2 and AMAGINE-3 included ustekinumab as a comparison up to week 52.

In the initial 12-week period of the phase 2 study, brodalumab was given in dosages of 70 mg, 140 mg or 210 mg every 2 weeks (with an additional dose during the first week) or in a dosage of 280 mg every 4 weeks. In AMAGINE-1 patients were given brodalumab 140 mg or 210 mg every 2 weeks (with an additional dose during the first week) until the end of the open-label extension (week 266). In AMAGINE-2 and AMAGINE-3, patients were given brodalumab 140 or 210 mg every two weeks (with the additional first week dose) until week 12. From week 12 to 266, patients given brodalumab received 140 mg every 2 weeks, every 4 weeks or every 8 weeks or 210 mg every 2 weeks.

In the ustekinumab group, doses were given according to the label: 45 mg in patients with body weight less than 100 kg and 90 mg in patients more than 100 kg, given on day 1, week 4 and every 12 weeks after until week 52.

During the initial 12-weeks of the studies, four adjudicated malignancies (three cases of NMSCs and one SEER-adjudicated malignancy) were reported over a total of 688 PY among all patients receiving brodalumab. There were no malignancies in the placebo group over a total of 195 PY and one SEER-adjudicated malignancy over a total of 140 PY in the ustekinumab group.

Through 52 weeks, exposure-adjusted adjudicated malignancy rates were lower in the brodalumab group (0.9 events per 100 PY) than in the ustekinumab group (2.6 events per 100 PY).

In the long-term analysis of 4,464 patients given brodalumab over 8,655 PY of exposure, the malignancy event rate was 0.9 per 100 PY. The event rate for NMSCs was 0.6 per 100 PY. Three NMSCs were reported in patients with prior malignancy, receiving 210 mg of brodalumab every two weeks through 52 weeks. Thirty-seven patients experienced SEER-adjudicated malignancies over a total of 9,174 PY of exposure.

“Overall, there is limited clinical evidence that use of biologic treatments for psoriasis increase malignancy risk,” Alice Gottlieb, MD, PhD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues wrote in the study. “Longer follow-up and real-world evidence are needed to characterize the long-term risk of malignancy with brodalumab.” – by Kaitlin McGee

Disclosures: Gottlieb reports she has served as a consultant or an advisory board member for Janssen, Celgene, Bausch Health, Bristol-Myers Squibb, Beiersdorf, AbbVie, UCB, Novartis, Incyte, Eli Lilly, Dr. Reddy’s Laboratories, Dermira, Allergan, Sun Pharma, XBiotech, Leo Pharmaceuticals, Avotres Therapeutics and Boehringer Ingelheim and has received research or educational grants from Janssen, Incyte, Novartis, XBiotech, UCB and Boehringer Ingelheim. Please see the study for all other authors’ relevant financial disclosures.