Ixekizumab Is Effective in Subjects With Moderate to Severe Plaque Psoriasis With Significant Nail Involvement: Results From UNCOVER 3. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials A prospective phase III, randomized, double‐blind, placebo‐controlled study of brodalumab in patients with moderate‐to‐severe plaque psoriasis First‐in‐human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL‐17A and IL‐17F, in mild psoriasis Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: Results from 3 phase III psoriasis clinical trials. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab′ certolizumab pegol: results of a phase II randomized, placebo‐controlled trial with a re‐treatment extension Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis. Efficacy and safety of guselkumab, an anti‐interleukin‐23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double‐blind, placebo‐ and active comparator–controlled VOYA Efficacy and safety of guselkumab, an anti‐interleukin‐23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double‐blinded, placebo‐ and active comparator–controlled VOYAGE 1 trial Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. Risankizumab versus Ustekinumab for Moderate‐to‐Severe Plaque Psoriasis
BACKGROUND Ixekizumab , a monoclonal antibody that selectively targets interleukin-17A , has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis . The lifetime incidence of psoriatic nail disease is 80%-90 % of patients , and approximately 50 % of patients with psoriasis have nail involvement . MATERIAL S AND METHODS The design of UNCOVER-3 , a Phase 3 , multicenter , double-blind , placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis , has been published previously . Patients were r and omized to receive blinded placebo , etanercept ( 50 mg twice weekly ) or 80 mg ixekizumab every 2 weeks ( IXEQ2W ) or every 4 weeks ( IXEQ4W ) for 12 weeks . At week 12 , all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60 . In this 60-week post hoc subset analysis , we evaluated only those patients with significant baseline nail involvement , defined as fingernail NAPSI ≥16 and at least 4 fingernails involved .  RESULTS Ixekizumab Q2W or Q4W result ed in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration , as measured by percent NAPSI reduction ( IXEQ2W 39 % improvement , IXEQ4W 40 % , etanercept 28 % , placebo -4.7 % ) . At week 24 , significantly more patients receiving ixekizumab exhibited no signs of nail involvement ( IXEQ2W/Q4W 34 % , IXEQ4W/Q4W 30 % ) . Similar gains were observed at 60 weeks in all treatment groups . CONCLUSION Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo . Continued improvement in fingernail psoriasis with ixekizumab was observed , with > 50 % of patients achieving complete fingernail psoriasis resolution ( NAPSI=0 ) at week 60 . J Drugs Dermatol . 2016;15(8):958 - 961 BACKGROUND Brodalumab ( anti-interleukin-17-receptor antibody ) was effective in treating moderate to severe psoriasis in a 12-week , dose-ranging , placebo-controlled trial . OBJECTIVE We sought to evaluate efficacy and safety of long-term brodalumab treatment . METHODS In this interim analysis at week 120 of an open-label extension study , patients received brodalumab 210 mg every 2 weeks . Protocol amendments reduced the dose ( 140 mg ) in patients weighing 100 kg or less and subsequently increased the dose ( 210 mg ) in patients with inadequate responses . Efficacy was measured by static physician global assessment and 75 % or greater , 90 % or greater , or 100 % improvement in Psoriasis Area and Severity Index score ( PASI-75 , PASI-90 , and PASI-100 , respectively ) . RESULTS Of 181 patients , 144 completed week 120 .  Static physician global assessment scores of clear/almost clear and clear were achieved by 90 % and 63 % of patients , respectively , at week 12 and by 72 % and 51 % at week 120 . The PASI-75 , PASI-90 , and PASI-100 response rates at week 12 ( 95%/85%/63 % ) were sustained through week 120 ( 86%/70%/51 % ) . Most commonly reported adverse events were nasopharyngitis ( 26.5 % ) , upper respiratory tract infection ( 19.9 % ) , arthralgia ( 16.0 % ) , and back pain ( 11.0 % ) . Four patients had grade -2 absolute neutrophil count . LIMITATIONS There was no control group in this open-label extension . CONCLUSION Brodalumab demonstrated sustained clinical response and an acceptable safety profile through 120 weeks in patients with moderate to severe psoriasis BACKGROUND Tildrakizumab is a high-affinity , humanised , IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis . Previous research suggested clinical improvement with inhibition of interleukin 23 p19 . We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis . METHODS We did two three-part , parallel group , double-blind , r and omised controlled studies , reSURFACE 1 ( at 118 sites in Australia , Canada , Japan , the UK , and the USA ) and reSURFACE 2 ( at 132 sites in Europe , Israel , and the USA ) . Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis ( body surface area involvement ≥10 % , Physician 's Global Assessment [ PGA ] score ≥3 , and Psoriasis Area and Severity Index [ PASI ] score ≥12 ) were r and omised ( via interactive voice and web response system ) to tildrakizumab 200 mg , tildrakizumab 100 mg , or placebo in reSURFACE 1 ( 2:2:1 ) , or to tildrakizumab 200 mg , tildrakizumab 100 mg , placebo , or etanercept 50 mg ( 2:2:1:2 ) . R and omisation was done by region and stratified for bodyweight ( ≤90 kg or > 90 kg ) and previous exposure to biologics therapy for psoriasis . Investigators , participants , and study personnel were blinded to group allocation and remained blinded until completion of the studies . Assigned medication was identical in appearance and packaging . Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 ( weeks 12 and 16 for participants re-r and omised from placebo to tildrakizumab ; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2 ) . The co- primary endpoints were the proportion of patients achieving PASI 75 and PGA response ( score of 0 or 1 with ≥2 grade score reduction from baseline ) at week 12 . Safety was assessed in the all- participants -as-treated population , and efficacy in the full- analysis set . These trials are registered with Clinical Trials.gov , numbers NCT01722331 ( reSURFACE 1 ) and NCT01729754 ( reSURFACE 2 ) . These studies are completed , but extension studies are ongoing . FINDINGS reSURFACE 1 ran from Dec 10 , 2012 , to Oct 28 , 2015 . reSURFACE 2 ran from Feb 12 , 2013 , to Sept 28 , 2015 . In reSURFACE 1 , 772 patients were r and omly assigned , 308 to tildrakizumab 200 mg , 309 to tildrakizumab 100 mg , and 155 to placebo . At week 12 , 192 patients ( 62 % ) in the 200 mg group and 197 patients ( 64 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . 182 patients ( 59 % ) in the 200 mg group and 179 patients ( 58 % ) in the 100 mg group achieved PGA responses , compared with 11 patients ( 7 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . In reSURFACE 2 , 1090 patients were r and omly assigned , 314 to tildrakizumab 200 mg , 307 to tildrakizumab 100 mg , 156 to placebo , and 313 to etanercept . At week 12 , 206 patients ( 66 % ) in the 200 mg group , and 188 patients ( 61 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group and 151 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept ) . 186 patients ( 59 % ) in the 200 mg group , and 168 patients ( 59 % ) [ corrected ] in the 100 mg group achieved a PGA response , compared with 7 patients ( 4 % ) in the placebo group and 149 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept ) . Serious adverse events were similar and low in all groups in both trials . One patient died in reSURFACE 2 , in the tildrakizumab 100 mg group ; the patient had alcoholic cardiomyopathy and steatohepatitis , and adjudication was unable to determine the cause of death . INTERPRETATION In two phase 3 trials , tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis . FUNDING Merck & The interleukin‐17 cytokine family plays a central role in psoriasis pathogenesis Aims To assess safety , pharmacokinetics ( PK ) and clinical efficacy of bimekizumab ( formerly UCB4940 ) , a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)‐17A and IL‐17F , in subjects with mild plaque psoriasis . Methods R and omized , double‐blind , first‐in‐human study of bimekizumab in 39 subjects who received single‐dose intravenous bimekizumab ( 8–640 mg ) or placebo ( NCT02529956 ) .  Results Bimekizumab demonstrated dose‐proportional linear PK and was tolerated across the dose range assessed . No subject discontinued due to treatment‐emergent adverse events and no severe adverse events were reported . Bimekizumab demonstrated fast onset of clinical ly‐meaningful effects on skin of patients with mild psoriasis  as early as Week 2 . Maximal improvements ( 100 % or near 100 % reductions from baseline ) in all measures of disease activity were observed between Weeks 8–12 in subjects receiving 160–640 mg bimekizumab . The duration of effect at doses ≥160 mg was evident up to Weeks 12–20 after a single intravenous dose , dependent on endpoint . Conclusions This is the first study to demonstrate the safety , tolerability and clinical efficacy of a dual IL‐17A and IL‐17F inhibitor , in subjects with mild psoriasis .  Bimekizumab showed fast onset of clinical ly‐meaningful efficacy by Week 2 , with a maximal or near‐maximal magnitude of response that was maintained up to study Weeks 12–20 . These findings support the continued clinical development of bimekizumab for diseases mediated by both IL‐17A and IL‐17F , including psoriasis Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn 's disease . Design In a double-blind , r and omised , placebo-controlled proof-of-concept study , 59 patients with moderate to severe Crohn 's disease ( Crohn 's Disease Activity Index ( CDAI ) ≥220 to ≤450 ) were assigned in a 2:1 ratio to 2 × 10 mg/kg intravenous secukinumab or placebo . The primary end point , addressed by Bayesian statistics augmented with historical placebo information , was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6 . Ancillary analyses explored associations of 35 c and i date genetic polymorphisms and faecal calprotectin response . Results 59 patients ( 39 secukinumab , 20 placebo , mean baseline CDAI 307 and 301 , respectively ) were recruited . 18/59 ( 31 % ) patients discontinued prematurely ( 12/39 ( 31 % ) secukinumab , 6/20 ( 30 % ) placebo ) , 10/59 ( 17 % ) due to insufficient therapeutic effect ( 8/39 ( 21 % ) secukinumab , 2/20 ( 10 % ) placebo ) . Fourteen serious adverse events occurred in 10 patients ( seven secukinumab , three placebo ) ; 20 infections , including four local fungal infections , were seen on secukinumab versus none on placebo . Primary end point analysis estimated < 0.1 % probability ( ∆CDAI ( SD ) = 33.9 ( 19.7 ) , 95 % credible interval −4.9 to 72.9 ) that secukinumab  reduces CDAI by ≥50 points more than placebo . Secondary area under the curve analysis ( weeks 4–10 ) showed a significant difference ( mean ΔCDAI=49 ; 95 % CI ( 2 to 96 ) , p=0.043 ) in favour of placebo . Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers ( CRP≥10 mg/l and /or faecal calprotectin≥200 ng/ml ; mean ΔCDAI=62 ; 95 % CI ( −1 to 125 ) , p=0.054 in favour of placebo ) . Absence of the minor allele of tumour necrosis factor-like lig and 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 ( p=0.00035 Bonferroni-corrected ) . Conclusions Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo . Clinical trial registration This trial was registered at Clinical Trial.gov with the number NCT01009281 BACKGROUND Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A . We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis . METHODS In two prospect i ve , double-blind , multicentre , phase 3 studies ( UNCOVER-2 and UNCOVER-3 ) , eligible patients were aged 18 years or older , had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline ( r and omisation ) , 10 % or greater body-surface area involvement at both screening and baseline visits , at least a moderate clinical severity as measured by a static physician global assessment ( sPGA ) score of 3 or more , and a psoriasis area and severity index ( PASI ) score of 12 . Participants were r and omly assigned ( 1:2:2:2 ) by computer-generated r and om sequence with an interactive voice response system to receive subcutaneous placebo , etanercept ( 50 mg twice weekly ) , or one injection of 80 mg ixekizumab every 2 weeks , or every 4 weeks after a 160 mg starting dose . Blinding was maintained with a double-dummy design . Co primary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75 % or greater improvement in PASI at week 12 . Analysis was by intention to treat . These trials are registered with Clinical Trials.gov , numbers NCT01597245 and NCT01646177 . FINDINGS Between May 30 , 2012 , and Dec 30 , 2013 , 1224 patients in UNCOVER-2 were r and omly assigned to receive subcutaneous placebo ( n=168 ) , etanercept ( n=358 ) , or ixekizumab every 2 weeks ( n=351 ) or every 4 weeks ( n=347 ) ; between Aug 11 , 2012 , and Feb 27 , 2014 , 1346 patients in UNCOVER-3 were r and omly assigned to receive placebo ( n=193 ) , etanercept ( n=382 ) , ixekizumab every 2 weeks ( n=385 ) , or ixekizumab every 4 weeks ( n=386 ) . At week 12 , both primary endpoints were met in both studies . For UNCOVER-2 and UNCOVER-3 respectively , in the ixekizumab every 2 weeks group , PASI 75 was achieved by 315 ( response rate 89·7 % ; [ effect size 87·4 % ( 97·5 % CI 82·9 - 91·8 ) vs placebo ; 48·1 % ( 41·2 - 55·0 ) vs etanercept ] ) and 336 ( 87·3 % ; [ 80·0 % ( 74·4 - 85·7 ) vs placebo ; 33·9 % ( 27·0 - 40·7 ) vs etanercept ] ) patients ; in the ixekizumab every 4 weeks group , by 269 ( 77·5 % ; [ 75·1 % ( 69·5 - 80·8 ) vs placebo ; 35·9 % ( 28·2 - 43·6 ) vs etanercept ] ) and 325 ( 84·2 % ; [ 76·9 % ( 71·0 - 82·8 ) vs placebo ; 30·8 % ( 23·7 - 37·9 ) vs etanercept ] ) patients ; in the placebo group , by four ( 2·4 % ) and 14 ( 7·3 % ) patients ; and in the etanercept group by 149 ( 41·6 % ) and 204 ( 53·4 % ) patients ( all p<0·0001 vs placebo or etanercept ) . In the ixekizumab every 2 weeks group , sPGA 0/1 was achieved by 292 ( response rate 83·2 % ; [ effect size 80·8 % ( 97·5 % CI 75·6 - 86·0 ) vs placebo ; 47·2 % ( 39·9 - 54·4 ) vs etanercept ] ) and 310 ( 80·5 % ; [ 73·8 % ( 67·7 - 79·9 ) vs placebo ; 38·9 % ( 31·7 - 46·1 ) vs etanercept ] ) patients ; in the ixekizumab every 4 weeks group by 253 ( 72·9 % ; [ 70·5 % ( 64·6 - 76·5 ) vs placebo ; 36·9 % ( 29·1 - 44·7 ) vs etanercept ] ) and 291 ( 75·4 % ; [ 68·7 % ( 62·3 - 75·0 ) vs placebo ; 33·8 % ( 26·3 - 41·3 ) vs etanercept ] ) patients ; in the placebo group by four ( 2·4 % ) and 13 ( 6·7 % ) patients ; and in the etanercept group by 129 ( 36·0 % ) and 159 ( 41·6 % ) patients ( all p<0·0001 vs placebo or etanercept ) . In combined studies , serious adverse events were reported in 14 ( 1·9 % ) of 734 patients given ixekizumab every 2 weeks , 14 ( 1·9 % ) of 729 given ixekizumab every 4 weeks , seven ( 1·9 % ) of 360 given placebo , and 14 ( 1·9 % ) of 739 given etanercept ; no deaths were noted . INTERPRETATION Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies . These studies show that selectively neutralising interleukin 17A with a high affinity antibody potentially gives patients with psoriasis a new and effective biological therapy option . FUNDING Eli Lilly and BACKGROUND Itch is a prevalent symptom of psoriasis that impacts quality of life . OBJECTIVE We sought to describe improvements in itch severity , skin pain , and bothersomeness of skin appearance caused by psoriasis among patients who received ixekizumab , etanercept , or placebo in three 12-week , phase III clinical trials ( UNCOVER-1 , -2 , and -3 ) . METHODS The itch numeric rating scale evaluated psoriasis itch severity in all 3 trials . Skin pain was assessed by skin pain visual analog scale . Bothersomeness because of redness/discoloration , thickness , and scaling/flaking was assessed with the Psoriasis Skin Appearance Bothersomeness instrument . Psoriasis skin appearance bothersomeness and skin pain were assessed at baseline and week 12 ; itch numeric rating scale score was assessed at baseline and weeks 1 , 2 , 4 , 8 , and 12 . RESULTS Patients who received ixekizumab  demonstrated statistically significant improvements ( P < .001 ) in itch severity , reduction in skin pain , and degree of bothersomeness compared with those who received etanercept or placebo . Clinical ly meaningful improvements in itch severity were achieved as early as week 1 . LIMITATIONS Longer-term evaluations of psoriasis symptom improvement with ixekizumab treatment are needed . CONCLUSION After treatment with ixekizumab , patients reported fast , significant , and clinical ly meaningful improvements in itch severity and other psoriasis-related symptoms such as skin pain and skin appearance bothersomeness Background Certolizumab pegol ( CZP ) is a PEGylated antitumour necrosis factor agent BACKGROUND Novel therapies are needed for difficult-to-treat population s of patients with psoriasis . OBJECTIVE We sought to assess the efficacy and safety of the interleukin-17 Receptor A inhibitor brodalumab in patients with psoriasis with or without a self-reported history of psoriatic arthritis ( PsA ) and with or without a history of biologic use . METHODS Subset analyses of a phase II , r and omized , double-blind , placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis were performed . Improvement from baseline in Psoriasis Area and Severity Index score of 75 % , 90 % , and 100 % at week 12 ; static Physician Global Assessment ( 0/1 ) score ; Dermatology Life Quality Index response ; and Psoriasis Symptom Inventory response were evaluated within subgroups . RESULTS Efficacy and quality -of-life measures were generally similar between subgroups of patients with or without a history of PsA and with or without a history of biologic use across brodalumab doses and were significantly higher among patients who received brodalumab 140 mg every 2 weeks or 210 mg every 2 weeks versus placebo . LIMITATIONS Differences between subgroups were not compared statistically , PsA was self-reported , only skin involvement/symptoms were reported , and reasons for discontinuation of prior biologic were not captured . CONCLUSION Brodalumab is efficacious in patients with psoriasis with or without a history of PsA or biologic use Background : Phase II data suggested that guselkumab , an anti‐interleukin‐23 monoclonal antibody , was efficacious in psoriasis . Objective : We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab , including interrupted treatment and switching adalimumab nonresponders to guselkumab . Methods : Patients were r and omized to guselkumab 100 mg ( weeks 0 and 4 , then every 8 weeks ; n = 496 ) ; placebo→guselkumab ( weeks 0 , 4 , and 12 then guselkumab at weeks 16 and 20 ; n = 248 ) ; or adalimumab ( 80 mg week 0 , then 40 mg week 1 , and every 2 weeks through week 23 ; n = 248 ) . At week 28 , guselkumab 90 % or greater improvement in Psoriasis Area and Severity Index ( PASI ) score from baseline ( PASI 90 ) responders were rer and omized to guselkumab or placebo with guselkumab after loss of response . Placebo→guselkumab responders and adalimumab responders received placebo , then guselkumab after loss of response . Nonresponders received guselkumab . Results : At week 16 , more patients receiving guselkumab achieved an Investigator Global Assessment ( IGA ) score 0/1 ( cleared/minimal ) ( 84.1 % vs 8.5 % ) and PASI 90 ( 70.0 % vs 2.4 % ) versus placebo ( co primary end points ) . Guselkumab was superior to adalimumab at week 16 ( IGA score 0/1 , 75 % or greater improvement in PASI score from baseline , and PASI 90 ) and week 24 ( IGA score 0/1 and 0 , PASI 90 , 100 % improvement in PASI score from baseline ) ( P < .001 ) . From weeks 28 to 48 , better persistence of response was observed in guselkumab maintenance versus withdrawal groups ( P < .001 ) . Of adalimumab nonresponders who switched to guselkumab , 66.1 % achieved PASI 90 at week 48 . Guselkumab improved patient‐reported outcomes . Adverse events were comparable among groups . Limitations : One‐year follow‐up limits retreatment data . Conclusions : Guselkumab is a highly effective , well‐tolerated , maintenance therapy , including in adalimumab nonresponders Background : Guselkumab , an interleukin‐23 blocker , was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial . Objectives : We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year . Methods : Patients were r and omized to guselkumab  100 mg ( weeks 0 and 4 , then every 8 weeks ; n = 329 ) ; placebo→guselkumab ( weeks 0 , 4 , and 12 then guselkumab at weeks 16 and 20 , then every 8 weeks ; n = 174 ) ; or adalimumab ( 80 mg week 0 , 40 mg week 1 , then 40 mg every 2 weeks through week 47 ; n = 334 ) . Physician‐reported outcomes ( Investigator Global Assessment , Psoriasis Area and Severity Index [ PASI ] ) , patient‐reported outcomes ( Dermatology Life Quality Index , Psoriasis Symptoms and Signs Diary ) , and safety were evaluated through week 48 . Results : Guselkumab was superior ( P < .001 ) to placebo at week 16 ( 85.1 % vs 6.9 % [ Investigator Global Assessment score of 0/1 ( cleared/minimal ) ] and 73.3 % vs 2.9 % [ 90 % or greater improvement in PASI score from baseline ( PASI 90 ) ] ) . Guselkumab was also superior ( P < .001 ) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 ( 85.1 % vs 65.9 % and 73.3 % vs 49.7 % ) , week 24 ( 84.2 % vs 61.7 % and 80.2 % vs 53.0 % ) , and week 48 ( 80.5 % vs 55.4 % and 76.3 % vs 47.9 % ) . Furthermore , guselkumab  significantly improved patient‐reported outcomes through week 48 . Adverse event rates were comparable between treatments . Limitations : Analyses were limited to 48 weeks . Conclusions : Guselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year BACKGROUND Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis . METHODS In two phase 3 studies ( AMAGINE-2 and AMAGINE-3 ) , patients with moderate-to-severe psoriasis were r and omly assigned to receive brodalumab ( 210 mg or 140 mg every 2 weeks ) , ustekinumab ( 45 mg for patients with a body weight ≤100 kg and 90 mg for patients > 100 kg ) , or placebo . At week 12 , patients receiving  brodalumab were r and omly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks , every 4 weeks , or every 8 weeks ; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks , and patients receiving placebo received 210 mg of brodalumab every 2 weeks . The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75 % reduction in the psoriasis area- and -severity index score ( PASI 75 ) and a static physician 's global assessment ( sPGA ) score of 0 or 1 ( clear or almost clear skin ) , as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100 % reduction in PASI score ( PASI 100 ) . RESULTS At week 12 , the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo ( 86 % and 67 % , respectively , vs. 8 % [ AMAGINE-2 ] and 85 % and 69 % , respectively , vs. 6 % [ AMAGINE-3 ] ; P<0.001 ) ; the rates of sPGA scores of 0 or 1 were also higher with brodalumab ( P<0.001 ) . The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab ( 44 % vs. 22 % [ AMAGINE-2 ] and 37 % vs. 19 % [ AMAGINE-3 ] , P<0.001 ) . The PASI 100 response rates with 140 mg of brodalumab were 26 % in AMAGINE-2 ( P=0.08 for the comparison with ustekinumab ) and 27 % in AMAGINE-3 ( P=0.007 ) . Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo .  Mild or moderate c and ida infections were more frequent with brodalumab than with ustekinumab or placebo . Through week 52 , the rates of serious infectious episodes were 1.0 ( AMAGINE-2 ) and 1.3 ( AMAGINE-3 ) per 100 patient-years of exposure to brodalumab . CONCLUSIONS Brodalumab treatment result ed in significant clinical improvements in patients with moderate-to-severe psoriasis . ( Funded by Amgen ; AMAGINE-2 and AMAGINE-3 Clinical Trials.gov numbers , NCT01708603 and NCT01708629 . ) BACKGROUND Two phase 3 trials ( UNCOVER-2 and UNCOVER-3 ) showed that at 12 weeks of treatment , ixekizumab , a monoclonal antibody against interleukin-17A , was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis . We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials , as well as 12-week and 60-week data from a third phase 3 trial , UNCOVER-1 . METHODS We r and omly assigned 1296 patients in the UNCOVER-1 trial , 1224 patients in the UNCOVER-2 trial , and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo ( placebo group ) , 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg ( 2-wk dosing group ) , or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg ( 4-wk dosing group ) . Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were r and omly assigned to receive 50 mg of etanercept twice weekly . At week 12 in the UNCOVER-3 trial , the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60 ; at week 12 in the UNCOVER-1 and UNCOVER-2 trials , the patients who had a response to ixekizumab ( defined as a static Physicians Global Assessment [ sPGA ] score of 0 [ clear ] or 1 [ minimal psoriasis ] ) were r and omly reassigned to receive placebo , 80 mg of ixekizumab every 4 weeks , or 80 mg of ixekizumab every 12 weeks through week 60 . Co primary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75 % or greater reduction from baseline in Psoriasis Area and Severity Index ( PASI 75 ) at week 12 . RESULTS In the UNCOVER-1 trial , at week 12 , the patients had better responses to ixekizumab than to placebo ; in the 2-wk dosing group , 81.8 % had an sPGA score of 0 or 1 and 89.1 % had a PASI 75 response ; in the 4-wk dosing group , the respective rates were 76.4 % and 82.6 % ; and in the placebo group , the rates were 3.2 % and 3.9 % ( P<0.001 for all comparisons of ixekizumab with placebo ) . In the UNCOVER-1 and UNCOVER-2 trials , among the patients who were r and omly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks , 80 mg of ixekizumab every 12 weeks , or placebo , an sPGA score of 0 or 1 was maintained by 73.8 % , 39.0 % , and 7.0 % of the patients , respectively . Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60 , and at week 60 , at least 73 % had an sPGA score of 0 or 1 and at least 80 % had a PASI 75 response . Adverse events reported during ixekizumab use included neutropenia , c and idal infections , and inflammatory bowel disease . CONCLUSIONS In three phase 3 trials involving patients with psoriasis , ixekizumab was effective through 60 weeks of treatment . As with any treatment , the benefits need to be weighed against the risks of adverse events . The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known . ( Funded by Eli Lilly ; UNCOVER-1 , UNCOVER-2 , and UNCOVER-3 Clinical Trials.gov numbers NCT01474512 , NCT01597245 , and NCT01646177 , respectively . ) BACKGROUND Interleukin‐23 is thought to be critical to the pathogenesis of psoriasis . We compared risankizumab ( BI 655066 ) , a humanized IgG1 monoclonal antibody that inhibits interleukin‐23 by specifically targeting the p19 subunit and thus prevents interleukin‐23 signaling , and ustekinumab , an interleukin‐12 and interleukin‐23 inhibitor , in patients with moderate‐to‐severe plaque psoriasis . METHODS We r and omly assigned a total of 166 patients to receive subcutaneous injections of risankizumab ( a single 18‐mg dose at week 0 or 90‐mg or 180‐mg doses at weeks 0 , 4 , and 16 ) or ustekinumab ( 45 or 90 mg , according to body weight , at weeks 0 , 4 , and 16 ) . The primary end point was a 90 % or greater reduction from baseline in the Psoriasis Area and Severity Index ( PASI ) score at week 12 . RESULTS At week 12 , the percentage of patients with a 90 % or greater reduction in the PASI score was 77 % ( 64 of 83 patients ) for risankizumab ( 90‐mg and 180‐mg groups , pooled ) , as compared with 40 % ( 16 of 40 patients ) for ustekinumab ( P<0.001 ) ; the percentage of patients with a 100 % reduction in the PASI score was 45 % in the pooled 90‐mg and 180‐mg risankizumab groups , as compared with 18 % in the ustekinumab group . Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab . In the 18‐mg and 90‐mg risankizumab groups and the ustekinumab group , 5 patients ( 12 % ) , 6 patients ( 15 % ) , and 3 patients ( 8 % ) , respectively , had serious adverse events , including two basal‐cell carcinomas and one major cardiovascular adverse event ; there were no serious adverse events in the 180‐mg risankizumab group . CONCLUSIONS In this phase 2 trial , selective blockade of interleukin‐23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab . This trial was not large enough or of long enough duration to draw conclusions about safety . ( Funded by Boehringer Ingelheim ; Clinical Trials.gov number , NCT02054481 )
Many new biologics are being studied for use in psoriasis .
In this review , we evaluate and summarize findings about emerging biologic therapies for psoriasis .