Journal of Clinical and Aesthetic Dermatology

Updates on Psoriasis & Cutaneou Oncology

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S12 P r o c e e D i n G s JCAD jOUrnAl Of ClInICAl And AEsthEtIC dErMAtOlOgy september 2017 • volume 10 • number 9 • supplement was administered six times at Weeks 0, 2, 4, 8, 12, and 16; patients with plaque psoriasis for six or more months involving at least 10 percent of Bsa then entered a treatment- free period up to Week 32; those whose response was better than Pasi 75 at Week 32 were eligible to enter the open-label extension phase. in this phase, patients received 120mg of subcutaneous ixekizumab every four weeks up to Week 88, and then 80mg of subcutaneous ixekizumab every four weeks thereafter to Week 240 (data on fle with eli lilly and company). adverse events caused 10.8 percent of reported adverse events included alanine aminotransferase increase, hepatic enzyme increase, hidradenitis, invasive ductal breast carcinoma, nonsmall-cell lung metastatic cancer, osteomyelitis, psoriatic arthropathy, pyelonephritis, rectal adenocarcinoma, rectal adenoma, or a urinary tract obstruction (all <1%) or due to pregnancy (1.7%). no deaths were reported. treatment-emergent adverse events decreased from 60.0 percent in the frst year to 50.0 percent in the fourth year, but serious adverse events increased from 5.8 percent in the frst year to 10.5 percent in the fourth year. serious infections occurred in 5.0 percent of patients. Brodalumab. in two Phase 3 studies (the aMaGine2 (study of eecacy and safety of Brodalumab compared With Placebo and ustekinumab in Moderate to severe Plaque Psoriasis subjects nct01708603) and aMaGine3 (study of eecacy and safety of Brodalumab compared With Placebo and ustekinumab in Moderate to severe Plaque Psoriasis subjects nct01708629), patients with moderate-to- severe psoriasis were randomized into one of four groups: brodalumab 210mg every two weeks, brodalumab 140mg every two weeks, ustekinumab 45mg or 90mg depending on patient weight, or placebo. 13 after 12 weeks, brodalumab patients were randomized again to a maintenance dose of brodalumab of either 210mg every two weeks, 140mg every two weeks, 140mg every four weeks, and 140mg every eight weeks. ustekinumab patients continued to receive their regimen unchanged, while placebo patients were migrated to the 210mg brodalumab group. at 12 weeks, Pasi 75 response was higher in both 210mg and 140mg brodalumab groups (86% and 67%, respectively) than placebo (8%), p<0.001. the number of brodalumab patients with sPGa scores of 0 and 1 was signifcantly higher than placebo patients (p<0.001). at 12 weeks, Pasi 100 scores were achieved by signifcantly more brodalumab 210mg patients than ustekinumab patients in both studies (44% vs. 22%, respectively, and 37% vs. 19%, respectively, for aMaGine2 and aMaGine3, p<0.001 for both). for adverse events, neutropenia was more common with active treatments than placebo, and mild-to-moderate candidate infections occurred more often in brodalumab patients than ustekinumab or placebo patients. 13 safety concerns have arisen about brodalumab and its possible associations with depression and suicidality. in Phase 3 trials, the drug sponsor, amgen (thousand oaks, california), introduced a psychological survey instrument to better assess patients who might be at risk for these outcomes, but the intervention was not successful in identifying patients at risk. Despite robust eecacy results, studies were halted and amgen stopped developmental activities in the second quarter of 2015. amgen's partners continued development and submitted brodalumab to the fDa where it was reviewed in July of 2016. at the Dermatologic and ophthalmic Drugs advisory committee (DoDac) on July 19, 2016, 18 panelists recommended approval and 14 recommended a risk evaluation and mitigation strategy program (reMs) for brodalumab. thus, brodalumab was approved in february 2017 with a black-box warning, and a reMs program was established to restrict access. Patients who are prescribed brodalumab must be counseled and made aware of the mental health risks, and any new or worsening symptoms of depression or suicidality must be reported and patients will be referred, as appropriate, to competent mental health professionals. Patients must sign a patient-prescriber agreement in order to take brodalumab, which only certifed pharmacies may dispense. Brodalumab is contraindicated in patients with crohn's disease. 14 it has long been reported in the literature that psoriasis patients are at elevated risk for suicidality apart from any particular course of treatment. in a 1993 study, a survey of 217 psoriasis patients revealed that 9.7 percent said they had a wish to be dead and 5.5 percent had active suicidal ideation at the time of the survey. 15 these traits could be associated with a higher score for depression (p<0.0001) and higher self-ratings of severity of psoriasis (p<0.05). this important association between psoriasis and suicidality plus the potential risk factors specifcally associated with brodalumab remain to be further elucidated. treatment targets. the aaD published treatment targets for plaque psoriasis in 2017 that recommended Bsa as the preferred assessment metric and that treatments ought to attain an improvement of at least 75 percent every three months or the equivalent of achieving three percent Bsa improvement every three months. 16 the target response would be less than one percent of Bsa achieved at six months and then maintained every six months thereafter. 16 in order to meet this goal, dermatologists must select highly edective drugs for their psoriasis patients. an important metric for appropriate drug selection is the number needed to treat (nnt), which defnes the average number of patients who must be treated to achieve one additional good

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