Brodalumab achieved primary endpoints for moderate to severe psoriasis at 52 weeks

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.