Impact of previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE-2 and AMAGINE-3

BackgroundBiologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics. ObjectivesTo investigate the impact of previous biologic exposure on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. MethodsTwo placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with brodalumab [210mg or 140mg every 2weeks (Q2W)], ustekinumab or placebo. Efficacy end points included 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout. ResultsIn total, 493 patients [334 (27%) brodalumab 210mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40<bold></bold>9% and 39<bold></bold>5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21<bold></bold>1% and 17<bold></bold>0% with ustekinumab (both P<0<bold></bold>001). In patients where prior biologics had been successful or failed, 41<bold></bold>7% and 32<bold></bold>0% achieved PASI 100, compared with 21<bold></bold>1% and 11<bold></bold>3% with ustekinumab. Tolerability was similar, and did not appear to be influenced by previous treatment with biologics. ConclusionsThe efficacy of brodalumab 210mg Q2W was similar regardless of prior biological therapy (P=0<bold></bold>31, 0<bold></bold>32 and 0<bold></bold>64 for PASI 75, 90 and 100, respectively). Almost twice as many patients achieved PASI 100 or complete clearance with brodalumab at week 12 compared with ustekinumab; the differences were most noticeable where previous biologics had failed. Both treatments were well tolerated. What's already known about this topic? Biologics are highly effective in treating moderate-to-severe psoriasis. Efficacy rates may differ in patients with previous exposure to biologics, and in patients where previous biologics have failed. Published data are not conclusive regarding the effect of prior biologic use, and the efficacy of subsequent biologics in patients who had failed prior biological therapy has not been published. What does this study add? The efficacy of brodalumab was similar regardless of prior biological therapy. Approximately twice as many patients on brodalumab achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) compared with ustekinumab, irrespectively of whether they had prior biologic experience. The efficacy results in those patients who had failed previous biologics are most noteworthy, where the benefits are three times those seen with ustekinumab for PASI 100 (32<bold></bold>0% vs. 11<bold></bold>3%). Safety results were similar in patients who had previous exposure to biologics vs. those who were biologic naive.