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BACKGROUND	Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A .
BACKGROUND	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 prospective , 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 ( randomisation ) , 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 .
METHODS	Participants were randomly assigned ( 1:2:2:2 ) by computer-generated random 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 .
METHODS	Blinding was maintained with a double-dummy design .
METHODS	Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75 % or greater improvement in PASI at week 12 .
METHODS	Analysis was by intention to treat .
METHODS	These trials are registered with ClinicalTrials.gov , numbers NCT01597245 and NCT01646177 .
RESULTS	Between May 30 , 2012 , and Dec 30 , 2013 , 1224 patients in UNCOVER-2 were randomly 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 randomly assigned to receive placebo ( n = 193 ) , etanercept ( n = 382 ) , ixekizumab every 2 weeks ( n = 385 ) , or ixekizumab every 4 weeks ( n = 386 ) .
RESULTS	At week 12 , both primary endpoints were met in both studies .
RESULTS	For UNCOVER-2 and UNCOVER-3 respectively , in the ixekizumab every 2 weeks group , PASI 75 was achieved by 315 ( response rate 897 % ; [ effect size 874 % ( 975 % CI 829-918 ) vs placebo ; 481 % ( 412-550 ) vs etanercept ] ) and 336 ( 873 % ; [ 800 % ( 744-857 ) vs placebo ; 339 % ( 270-407 ) vs etanercept ] ) patients ; in the ixekizumab every 4 weeks group , by 269 ( 775 % ; [ 751 % ( 695-808 ) vs placebo ; 359 % ( 282-436 ) vs etanercept ] ) and 325 ( 842 % ; [ 769 % ( 710-828 ) vs placebo ; 308 % ( 237-379 ) vs etanercept ] ) patients ; in the placebo group , by four ( 24 % ) and 14 ( 73 % ) patients ; and in the etanercept group by 149 ( 416 % ) and 204 ( 534 % ) patients ( all p < 00001 vs placebo or etanercept ) .
RESULTS	In the ixekizumab every 2 weeks group , sPGA 0/1 was achieved by 292 ( response rate 832 % ; [ effect size 808 % ( 975 % CI 756-860 ) vs placebo ; 472 % ( 399-544 ) vs etanercept ] ) and 310 ( 805 % ; [ 738 % ( 677-799 ) vs placebo ; 389 % ( 317-461 ) vs etanercept ] ) patients ; in the ixekizumab every 4 weeks group by 253 ( 729 % ; [ 705 % ( 646-765 ) vs placebo ; 369 % ( 291-447 ) vs etanercept ] ) and 291 ( 754 % ; [ 687 % ( 623-750 ) vs placebo ; 338 % ( 263-413 ) vs etanercept ] ) patients ; in the placebo group by four ( 24 % ) and 13 ( 67 % ) patients ; and in the etanercept group by 129 ( 360 % ) and 159 ( 416 % ) patients ( all p < 00001 vs placebo or etanercept ) .
RESULTS	In combined studies , serious adverse events were reported in 14 ( 19 % ) of 734 patients given ixekizumab every 2 weeks , 14 ( 19 % ) of 729 given ixekizumab every 4 weeks , seven ( 19 % ) of 360 given placebo , and 14 ( 19 % ) of 739 given etanercept ; no deaths were noted .
CONCLUSIONS	Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies .
CONCLUSIONS	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 .
BACKGROUND	Eli Lilly and Co. .

