A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial The efficacy and safety of apremilast, etanercept and placebo in patients with moderate‐to‐severe plaque psoriasis: 52‐week results from a phase IIIb, randomized, placebo‐controlled trial (LIBERATE) Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis Etanercept as monotherapy in patients with psoriasis. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24‐week, randomized, controlled, investigator‐blinded pilot trial Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long‐term results from a randomized controlled, double‐blind, 52‐week, phase III trial in patients with moderate‐to‐severe plaque psoriasis 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 Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75–89 response: results from two phase 3 studies of secukinumab Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial) Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate‐to‐severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2) A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction Infliximab monotherapy in Japanese patients with moderate-to-severe plaque psoriasis and psoriatic arthritis. A randomized, double-blind, placebo-controlled multicenter trial. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate‐to‐severe plaque psoriasis up to 1 year: Results from the CLEAR study Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: Results from IXORA‐S, a phase 3 study Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate‐to‐severe chronic plaque psoriasis: a randomized, double‐blind, Fumaderm®‐ and placebo‐controlled trial (BRIDGE)
BACKGROUND Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy . OBJECTIVE The efficacy and safety of continuous ( every-8-week ) and intermittent ( as-needed ) maintenance regimens were compared . METHODS Patients with moderate-to-severe psoriasis ( n = 835 ) were r and omized to induction therapy ( weeks 0 , 2 , and 6 ) with infliximab 3 mg/kg or 5 mg/kg or placebo . Infliximab-treated patients were r and omized again at week 14 to continuous or intermittent maintenance regimens at their induction dose . RESULTS At week 10 , 75.5 % and 70.3 % of patients in the infliximab 5 mg/kg and 3 mg/kg groups , respectively , achieved PASI 75 ; 45.2 % and 37.1 % achieved PASI 90 ( vs 1.9 % [ PASI 75 ] and 0.5 % [ PASI 90 ] for placebo ; P < .001 ) . Through week 50 , PASI responses were better maintained with continuous compared with intermittent therapy within each dose , and with 5 mg/kg compared with 3 mg/kg continuous therapy . LIMITATIONS Longer term ( > 1 year ) maintenance therapy and further study of  infliximab serum concentrations over this period , in both PASI 75 responders and non-responders , would be preferable . CONCLUSIONS Through week 50 , response was best maintained with continuous infliximab therapy . Infliximab was generally well-tolerated in most patients Abstract Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , works intracellularly within immune cells to regulate inflammatory mediators . This phase 2b r and omized , placebo‐controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis . In total , 254 patients were r and omized to placebo , apremilast 20 mg b.i.d . ( apremilast 20 ) or apremilast 30 mg b.i.d . ( apremilast 30 ) through week 16 ; thereafter , all placebo patients were re‐r and omized to apremilast 20 or 30 through week 68 . Efficacy assessment s included achievement of 75 % or more reduction from baseline in Psoriasis Area and Severity Index score ( PASI‐75 ; primary ) and achievement of static Physician Global Assessment ( sPGA ; secondary ) score of 0 ( clear ) or 1 ( minimal ) at week 16 . Safety was assessed through week 68 . At week 16 , PASI‐75 response rates were 7.1 % ( placebo ) , 23.5 % ( apremilast 20 ; P = 0.0032 vs placebo ) and 28.2 % ( apremilast 30 ; P = 0.0003 vs placebo ) ; sPGA response rates ( score of 0 or 1 ) were 8.8 % ( placebo ) , 23.9 % ( apremilast 20 ; P = 0.0165 vs placebo ) and 29.6 % ( apremilast 30 ; P = 0.0020 vs placebo ) . Responses were maintained with apremilast through week 68 . Most common adverse events ( AEs ) with placebo , apremilast 20 and apremilast 30 ( 0–16 weeks ) were nasopharyngitis ( 8.3 % , 11.8 % , 11.8 % ) , diarrhea ( 1.2 % , 8.2 % , 9.4 % ) , and abdominal discomfort ( 1.2 % , 1.2 % , 7.1 % ) , respectively . Exposure‐adjusted incidence of these AEs did not increase with continued apremilast treatment ( up to 68 weeks ) . Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies Background Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , has demonstrated efficacy in patients with moderate‐to‐severe psoriasis . Objective Evaluate efficacy and safety of apremilast vs. placebo in biologic‐naive patients with moderate‐to‐severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb , r and omized , double‐blind , placebo‐controlled study ( NCT01690299 ) . Methods Two hundred and fifty patients were r and omized to placebo ( n = 84 ) , apremilast 30 mg BID ( n = 83 ) or etanercept 50 mg QW ( n = 83 ) through Week 16 ; thereafter , all patients continued or switched to apremilast through Week 104 . The primary efficacy endpoint was achievement of PASI‐75 at Week 16 with apremilast vs. placebo . Secondary endpoints included achievement of PASI‐75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16 . Outcomes were assessed through Week 52 . This study was not design ed for apremilast vs. etanercept comparisons . Results At Week 16 , PASI‐75 achievement was greater with apremilast ( 39.8 % ) vs. placebo ( 11.9 % ; P < 0.0001 ) ; 48.2 % of patients achieved PASI‐75  with etanercept ( P < 0.0001 vs. placebo ) . PASI‐75 response was maintained in 47.3 % ( apremilast/apremilast ) , 49.4 % ( etanercept/apremilast ) and 47.9 % ( placebo/apremilast ) of patients at Week 52 . Most common adverse events ( ≥5 % ) with apremilast , including nausea , diarrhoea , upper respiratory tract infection , nasopharyngitis , tension headache and headache , were mild or moderate in severity ; diarrhoea and nausea generally resolved in the first month . No new safety or tolerability issues were observed through Week 52 with apremilast . Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic‐naive patients with psoriasis , which was sustained over 52 weeks , and demonstrated safety consistent with the known safety profile of apremilast . Switching from etanercept to apremilast did not result in any new or clinical ly significant safety findings , and efficacy was maintained with apremilast through Week 52 Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies . The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study BACKGROUND Inflammatory cytokines such as tumor necrosis factor ( TNF ) have been implicated in the pathogenesis of psoriasis . We evaluated the safety and efficacy of etanercept , a TNF antagonist , for the treatment of plaque psoriasis . METHODS In this 24-week , double-blind study , 672 patients underwent r and omization and 652 either received placebo or received etanercept subcutaneously at a low dose ( 25 mg once weekly ) , a medium dose ( 25 mg twice weekly ) , or a high dose ( 50 mg twice weekly ) . After 12 weeks , patients in the placebo group began twice-weekly treatment with 25 mg of etanercept . The primary measure of clinical response was the psoriasis area- and -severity index . RESULTS At week 12 , there was an improvement from base line of 75 percent or more in the psoriasis area- and -severity index in 4 percent of the patients in the placebo group , as compared with 14 percent of those in the low-dose -- etanercept group , 34 percent in the medium-dose -- etanercept group , and 49 percent in the high-dose-etanercept group ( P<0.001 for all three comparisons with the placebo group ) . The clinical responses continued to improve with longer treatment . At week 24 , there was at least a 75 percent improvement in the psoriasis area- and -severity index in 25 percent of the patients in the low-dose group , 44 percent of those in the medium-dose group , and 59 percent in the high-dose group . The responses as measured by improvements in the psoriasis area- and -severity index were paralleled by improvements in global assessment s by physicians and the patients and in quality -of-life measures .  Etanercept was generally well tolerated . CONCLUSIONS The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks BACKGROUND New therapeutic options are needed for patients with psoriasis .  Tofacitinib , an oral Janus kinase inhibitor , is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis . In this study , we aim ed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population . METHODS In this phase 3 , r and omised , multicentre , double-dummy , placebo-controlled , 12-week , non-inferiority trial , adult patients with chronic stable plaque psoriasis ( for ≥12 months ) who were c and i date s for systemic or phototherapy and had a Psoriasis Area and Severity Index ( PASI ) score of 12 or higher and a Physician 's Global Assessment ( PGA ) of moderate or severe , and had failed to respond to , had a contraindication to , or were intolerant to at least one conventional systemic therapy , were enrolled from 122 investigational dermatology centres worldwide . Eligible patients were r and omly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals , etanercept 50 mg subcutaneously twice weekly at about 3 - 4 day intervals , or placebo . R and omisation was done by a computer-generated r and omisation schedule , and all patients and study personnel were masked to treatment assignment . The co- primary endpoints were the proportion of patients at week 12 with at least a 75 % reduction in the PASI score from baseline ( PASI75 response ) and the proportion of patients achieving a PGA score of " clear " or " almost clear " ( PGA response ) , analysed in the full analysis set ( all patients who were r and omised and received at least one dose of study drug ) . This study is registered with Clinical Trials.gov , number NCT01241591 . FINDINGS Between Nov 29 , 2010 , and Sept 13 , 2012 , we enrolled 1106 eligible adult patients with chronic plaque psoriasis and r and omly assigned them to the four treatment groups ( 330 to tofacitinib 5 mg twice daily , 332 to tofacitinib 10 mg twice daily , 336 to etanercept 50 mg twice weekly , and 108 to placebo ) . Of these patients , 1101 actually received their assigned study medication ( 329 in the tofactinib 5 mg group , 330 in the tofacitinib 10 mg group , 335 in the etanercept group , and 107 in the placebo group ) . At week 12 , PASI75 responses were recorded in 130 ( 39·5 % ) of 329 patients in the tofacitinib 5 mg group , 210 ( 63·6 % ) of 330 in the tofacitinib 10 mg group , 197 ( 58·8 % ) of 335 in the etanercept group , and six ( 5·6 % ) of 107 in the placebo group . A PGA response was achieved by 155 ( 47·1 % ) of 329 patients in the tofacitinib 5 mg group , 225 ( 68·2 % ) of 330 in the tofacitinib 10 mg group , 222 ( 66·3 % ) of 335 in the etanercept group , and 16 ( 15·0 % ) of 107 in the placebo group . The rate of adverse events was similar across the four groups , with serious adverse events occurring in seven ( 2 % ) of 329 patients in the tofacitinib 5 mg group , five ( 2 % ) of 330 in the tofacitinib 10 mg group , seven ( 2 % ) of 335 in the etanercept group , and two ( 2 % ) of 107 in the placebo group . Three ( 1 % ) of 329 patients in the tofacitinib 5 mg group , ten ( 3 % ) of 330 in the tofacitinib 10 mg group , 11 ( 3 % ) of 335 in the etanercept group , and four ( 4 % ) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events . INTERPRETATION In patients with moderate-to-severe plaque psoriasis , the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo , but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly . The adverse event rates over 12 weeks were similar for tofacitinib and etanercept . This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis . FUNDING Pfizer BACKGROUND Tumour necrosis factor alpha ( TNFalpha ) is thought to play a part in the pathogenesis of psoriasis . We assessed the efficacy and safety of continuous treatment with infliximab , a monoclonal antibody that binds to and neutralises the activity of TNFalpha , in patients with psoriasis . METHODS In this phase III , multicentre , double-blind trial , 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 , then every 8 weeks to week 46 . At week 24 , placebo-treated patients crossed over to infliximab treatment .  Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index ( PASI ) and nail psoriasis severity index ( NAPSI ) , respectively . The primary endpoint , analysed on an intention-to-treat-basis , was the proportion of patients achieving at least a 75 % improvement in PASI from baseline to week 10 . FINDINGS At week 10 , 80 % ( 242/301 ) of patients treated with infliximab achieved at least a 75 % improvement from their baseline PASI ( PASI 75 ) and 57 % ( 172/301 ) achieved at least a 90 % improvement ( PASI 90 ) , compared with 3 % and 1 % in the placebo group , respectively ( p<0.0001 ) . At week 24 , PASI 75 ( 82 % for infliximab vs 4 % for placebo ) and PASI 90 ( 58%vs 1 % ) were maintained ( p<0.0001 ) . At week 50 , 61 % achieved PASI 75 and 45 % achieved PASI 90 in the infliximab group . Infliximab was generally well tolerated in most patients . INTERPRETATION Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis , with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents . No r and omized controlled trials have been published combining biologics with conventional agents for psoriasis BACKGROUND Biologic agents offer a range of new therapeutic options for patients with psoriasis ; however , the relative benefit-risk profiles of such therapies are not well known . We compared two biologic agents , ustekinumab ( an interleukin-12 and interleukin-23 blocker ) and etanercept ( an inhibitor of tumor necrosis factor alpha ) , for the treatment of psoriasis . METHODS We r and omly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab ( at weeks 0 and 4 ) or high-dose etanercept ( 50 mg twice weekly for 12 weeks ) . The primary end point was the proportion of patients with at least 75 % improvement in the psoriasis area- and -severity index ( PASI ) at week 12 ; a secondary end point was the proportion with cleared or minimal disease on the basis of the physician 's global assessment . Assessors were unaware of the treatment assignments . The efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12 . RESULTS There was at least 75 % improvement in the PASI at week 12 in 67.5 % of patients who received 45 mg of ustekinumab and 73.8 % of patients who received 90 mg , as compared with 56.8 % of those who received etanercept ( P=0.01 and P<0.001 , respectively ) . Similarly , 65.1 % of patients who received 45 mg of ustekinumab and 70.6 % of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician 's global assessment , as compared with 49.0 % of those who received etanercept ( P<0.001 for both comparisons ) . Among patients who did not have a response to etanercept , 48.9 % had at least 75 % improvement in the PASI within 12 weeks after crossover to ustekinumab . One or more adverse events occurred through week 12 in 66.0 % of patients who received 45 mg of ustekinumab and 69.2 % of patients who received 90 mg of ustekinumab and in 70.0 % who received etanercept ; 1.9 % , 1.2 % , and 1.2 % , respectively , had serious adverse events . Safety patterns were similar before and after crossover from etanercept to ustekinumab . CONCLUSIONS The efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high-dose etanercept over a 12-week period in patients with psoriasis . ( Clinical Trials.gov number , NCT00454584 . BACKGROUND Tumor necrosis factor-α is a key mediator in the pathogenesis of psoriasis . Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α . The purpose of this study was to vali date the efficacy and safety of 5 mg/kg infliximab therapy in Chinese patients with moderate to severe plaque psoriasis . METHODS In this multicenter , double-blind , placebo-controlled trial , 129 patients with moderate-to-severe psoriasis were r and omized to the induction therapy ( weeks 0 , 2 and 6 ) with infliximab 5 mg/kg ( n = 84 ) or placebo ( n = 45 ) , followed with infliximab 5 mg/kg scheduled at week 14 and week 22 in the infliximab group , and infliximab 5 mg/kg scheduled at weeks 10 , 12 and 16 in the placebo group . The primary end point was the proportion of patients who achieved at least 75 % improvement in Psoriasis Area and Severity Index ( PASI 75 response rate ) from baseline at week 10 . RESULTS At week 10 , 81.0 % of patients treated with infliximab ( 5 mg/kg ) achieved a 75 % or greater improvement compared with 2.2 % of patients treated with placebo ( P < 0.001 ) . A significant improvement in PASI , Physician 's Global Assessment ( PGA ) and Dermatology Life Quality Index ( DLQI ) , was seen from week 6 through week 14 in the infliximab group compared with the placebo group . Through week 22 , PASI , PGA , DLQI were well maintained . The incidence of adverse events for the infliximab treatment group was slightly higher in comparison to the placebo treatment group during the first 10 weeks without statistical significance . However , there were 3 cases of tuberculosis that developed during the 26 weeks treatment with infliximal . CONCLUSIONS Infliximab treatment was effective as induction and maintenance treatments for Chinese patients with moderate to severe plaque psoriasis . Most drug-induced adverse events were mild to moderate , and well tolerated . Screening for tuberculosis is essential and prophylactic treatment should be given if necessary Objective To evaluate the effect of secukinumab , an interleukin-17A inhibitor , on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis ( AS ) . Methods In the phase III MEASURE 1 study , patients were r and omised to receive intravenous secukinumab 10 mg/kg ( at baseline , week 2 and week 4 ) followed by subcutaneous secukinumab 150 mg ( intravenous 150 mg ; n=125 ) or 75 mg ( intravenous 75 mg ; n=124 ) every four weeks , or matched placebo ( n=122 ) . Placebo-treated patients were re-r and omised to subcutaneous secukinumab 150 or 75 mg from week 16 . Clinical efficacy assessment s included Assessment of SpondyloArthritis international Society 20 ( ASAS20 ) response rates through week 104 . Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Results 97 ( 77.6 % ) and 103 ( 83.1 % ) patients in the intravenous 150 mg and intravenous 75 mg groups , respectively , completed week 104 . In the full analysis set ( intent-to-treat ) , ASAS20 response rates at week 104 were 73.7 % and 68.0 % in the intravenous 150 mg and intravenous 75 mg groups , respectively . Among patients with evaluable X-rays who were originally r and omised to secukinumab  ( n=168 ) , mean change in mSASSS from baseline to week 104 was 0.30±2.53 . Serious adverse events were reported in 12.2 % and 13.4 % of patients in the 150 mg and 75 mg groups , respectively . Conclusions Secukinumab improved AS signs and symptoms through 2 years of therapy , with no unexpected safety findings . Data from this study suggest a low mean progression of spinal radiographic changes , which will need to be confirmed in longer-term controlled studies . Trial registration number NCT01358175 BACKGROUND Biologic therapies are used to treat moderate to severe psoriasis , but evidence from r and omized , controlled studies is lacking regarding scalp-related effectiveness . OBJECTIVE To evaluate the efficacy and safety of etanercept for scalp symptoms ( erythema , in duration , scale , and percentage of scalp involvement ) in patients with moderate to severe plaque psoriasis and scalp involvement . METHODS In this r and omized , placebo-controlled study , adult patients with stable plaque psoriasis and significant scalp symptoms received etanercept 50 mg twice weekly ( BIW ) by subcutaneous injection ( SC ) for 12 weeks , followed by etanercept 50 mg once weekly ( QW ) and placebo QW ( Group A , n = 62 ) or SC placebo BIW for 12 weeks , followed by etanercept 50 mg BIW for 12 weeks ( Group B , n = 62 ) . The primary end point was percentage change in Psoriasis Scalp Severity Index ( PSSI ) at week 12 . RESULTS Demographics and disease characteristics were balanced : 56 % men , 73 % white , median age 41 years , median BMI 30.2 kg/m(2 ) . At week 12 , mean PSSI improvement was 86.8 % ( st and ard deviation [ SD ] , 18.0 % ) in Group A and 20.4 % ( SD , 39.3 % ) in Group B ( P < .0001 ) . At week 24 , mean PSSI improvements were as follows : Group A , 90.6 % ( SD 13.1 % ) ; Group B , 79.1 % ( SD 33.6 % ) . At week 12 , 51 of 59 ( 86 % ) Group A patients and 7 of 61 ( 11 % ) Group B patients achieved PSSI 75 ( P < .0001 ) . Three patients ( 2.7 % ) reported 5 serious adverse events : cholecystitis/cholelithiasis , fall/rib fracture , and metastatic malignant melanoma . LIMITATIONS The study was insufficiently powered to detect rare adverse events potentially associated with etanercept . CONCLUSIONS Etanercept is an effective , well-tolerated treatment for plaque psoriasis involving the scalp ABP 501 , a U.S.A. Food and Drug Administration‐ and European Medicines Agency‐approved biosimilar , is highly similar to adalimumab in structure , function and pharmacokinetics . Background Certolizumab pegol ( CZP ) is a PEGylated antitumour necrosis factor agent Abstract Background : The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index ( PASI ) 90 response has provided the possibility of both greater skin clearance and increased quality of life ( QOL ) . Objective : To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks . Methods : Subjects achieving various levels of skin clearance ( PASI 90–100 or PASI 75–89 ) and Dermatology  Life Quality Index ( DLQI ) ( 0/1 ) response were compared using ERASURE and FIXTURE trial data . Similar analyses with IGA ratings of Clear or Almost Clear were performed . Results : Significantly more PASI 90–100 responders at week 12 had DLQI 0/1 response than PASI 75–89 ( 69.4 % vs. 47.1 % ; p < .001 ) and sustained DLQI 0/1 response at week 52 ( 74.0 % vs. 56.7 % ; p < .001 ) . IGA results were similar . Conclusions : These results show that PASI 90–100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75–89 when considering patients ’ QOL BACKGROUND Apremilast works intracellularly to regulate inflammatory mediators . OBJECTIVE ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis . METHODS This phase III , multicenter , double-blind , placebo-controlled study r and omized adults ( 2:1 ) to apremilast or placebo .  At week 16 , the placebo group switched to apremilast through week 32 , followed by a r and omized treatment withdrawal phase to week 52 . Binary end points were analyzed using χ(2 ) test ; continuous end points used analysis of covariance . RESULTS In all , 844 patients were r and omized ( n = 282 , placebo ; n = 562 , apremilast ) . At week 16 , significantly more patients taking apremilast achieved 75 % or greater reduction from baseline Psoriasis Area and Severity Index score ( PASI-75 ) ( 33.1 % ) versus placebo ( 5.3 % , P < .0001 ; primary end point ) . Most ( 61.0 % ) patients rer and omized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7 % rer and omized to placebo . Of patients rer and omized to apremilast at week 32 , mean percentage change from baseline PASI score was -88 % to -81 % ( weeks 32 - 52 ) . During the placebo-controlled period , 55.7 % and 69.3 % of patients r and omized to placebo and apremilast , respectively , had 1 or more adverse events . Most adverse events were mild/moderate in severity . No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period . LIMITATIONS Data were limited to 52 weeks and may not generalize to nonplaque psoriasis . CONCLUSIONS Apremilast was effective in moderate to severe plaque psoriasis Abstract Objective : To assess the efficacy and safety of two etanercept dose regimens for psoriasis treatment . Methods : Subjects were ≥18 years old with stable moderate-to-severe plaque psoriasis . Subjects were r and omised to etanercept 50 mg once weekly ( QW ) or 50 mg twice weekly ( BIW ) double-blind for 12 weeks , followed by 50 mg QW open label in all subjects through week 24 . Only mild topical corticosteroids were permitted on scalp , axillae and groin for first 12 weeks ; topical medications ( corticosteroids of all potencies , vitamin D analogues and combination products ) were allowed as needed for second 12 weeks at physicians ' discretion , consistent with “ real-world ” therapeutic practice . An independent ethics committee review ed and approved the study protocol . Results : At week 24 , 59.9 % and 78.2 % in the QW/QW and BIW/QW groups achieved PASI 75 improvement . Mean percentage PASI improvement in these groups was 58.5 % and 74.1 % at week 12 and 70.7 % and 81.3 % at week 24 . Although permitted from weeks 12 to 24 , topical agents were used in only 27.7 % and 22.6 % in the QW/QW and BIW/QW groups by week 24 . Conclusion : Both etanercept regimens were efficacious in moderate-to-severe psoriasis , although the BIW/QW regimen consistently provided higher response rates than the QW/QW regimen . More potent topical medications were used electively in < 25 % of subjects in each group BACKGROUND Apremilast , a small molecule specific inhibitor of phosphodiesterase 4 , works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production . OBJECTIVE Assess apremilast  efficacy and safety in moderate to severe plaque psoriasis . METHODS Phase II , 12-week , multicenter , double-blind , placebo-controlled , parallel-group , dose-comparison study of 259 subjects r and omized 1 : 1 : 1 to placebo , apremilast 20 mg QD or apremilast 20 mg BID . RESULTS More subjects receiving apremilast 20 mg BID achieved ≥ 75 % reduction in Psoriasis Area and Severity Index ( PASI-75 ) vs. placebo ( 24.4 % vs. 10.3 % ; P = 0.023 ) . A similar proportion of subjects receiving apremilast 20 mg QD and placebo achieved PASI-75 at week 12 [ 9/87 ( 10.3 % , each group ) ] . Mean per cent reduction in PASI from baseline was 17.4 % for placebo , 30.3 % for apremilast 20 mg QD ( P = 0.021 vs. placebo ) and 52.1 % for apremilast 20 mg BID ( P < 0.001 ) . Apremilast 20 mg BID significantly decreased mean body surface area involvement vs. placebo ( 30.8 % vs. 3.2 % ; P < 0.001 ) . The most common adverse events were headache , nasopharyngitis , diarrhoea and nausea . Most events ( > 90 % ) were mild to moderate and did not lead to study discontinuation . Serious adverse events occurred in four placebo subjects ( panic attack , hospitalization for rehabilitation , hospitalization for alcoholism , worsening psoriasis ) , one receiving apremilast 20 mg QD ( knee surgery ) and in one receiving apremilast 20 mg BID ( worsening psoriasis ) . The panic attack was considered treatment-related ; both cases of worsening psoriasis occurred after medication discontinuation . No deaths or opportunistic infections were reported . CONCLUSION Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis Apremilast , an oral phosphodiesterase 4 inhibitor , regulates immune responses associated with psoriasis Background In previous studies , etanercept significantly improved plaque psoriasis and was well tolerated BACKGROUND A clinical trial of infliximab in psoriasis has not yet been performed in Asian population s , although infliximab has been approved for the indications of psoriatic arthritis and plaque psoriasis in the US and the EU . OBJECTIVE This study aims to vali date the efficacy and safety of infliximab in Japanese patients with plaque psoriasis and psoriatic arthritis . METHODS Patients with moderate-to-severe psoriasis , including psoriatic arthritis , were r and omized to the induction therapy ( Weeks 0 , 2 and 6 ) with infliximab 5 mg/kg ( n=37 ) or placebo ( n=17 ) . For the maintenance therapy , infliximab was administered every 8 weeks from Week 14 to Week 62 in the infliximab group , and placebo was switched to infliximab in the placebo group starting at Week 16 . The primary efficacy endpoint was the proportion of patients who had achieved at least 75 % improvement in the psoriasis area and severity index ( PASI 75 response rate ) from baseline at Week 10 . RESULTS At Week 10 , a total of 68.6 % of patients receiving infliximab and none of those receiving placebo , achieved PASI 75 response ( p<0.001 ) . A significant improvement in PASI , PGA , DLQI , and patient 's pain assessment was seen from Week 6 through Week 14 in the infliximab group compared with the placebo group . Through Week 66 , PASI , PGA , DLQI as well as pain relief were better maintained . CONCLUSION Infliximab could provide a sustained improvement effect on skin and joint symptoms , and accordingly contributed to a sustained improvement in the QOL of patients with moderate-to-severe plaque psoriasis and psoriatic arthritis .  Infliximab was generally well tolerated in most patients . These results corresponded with the results of the trials in the US and the EU BACKGROUND Tumor necrosis factor-alpha is a key mediator in the pathogenesis of psoriasis . Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-alpha , blocking its biologic activity . OBJECTIVE The purpose of this study was to access the efficacy and safety of infliximab induction therapy for patients with severe plaque psoriasis . METHODS In this multicenter , double-blind , placebo-controlled trial , 249 patients with severe plaque psoriasis were r and omly assigned to receive intravenous infusions of either 3 or 5 mg/kg of infliximab or placebo given at weeks 0 , 2 , and 6 . The primary end point was the proportion of patients who achieved at least 75 % improvement in Psoriasis Area and Severity Index score from baseline at week 10 . At week 26 , patients whose Physician Global Assessment indicated moderate or severe disease were eligible for a single intravenous infusion of their assigned treatment to assess the safety of retreatment after a 20-week , treatment-free interval . RESULTS At week 10 , 72 % of patients treated with infliximab ( 3 mg/kg ) and 88 % of patients treated with infliximab ( 5 mg/kg ) achieved a 75 % or greater improvement from baseline in Psoriasis Area and Severity Index score compared with 6 % of patients treated with placebo ( P < .001 ) . Improvement was observed in both infliximab groups as early as 2 weeks . Overall , 63 % , 78 % , and 79 % of patients in the placebo , 3- , and 5-mg/kg groups , respectively , reported one or more adverse events . CONCLUSIONS Infliximab treatment result ed in a rapid and significant improvement in the signs and symptoms of psoriasis .  Infliximab was generally well tolerated Background : Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study , with comparable safety , in subjects with moderate‐to‐severe plaque psoriasis . Objective : To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks . Methods : Analysis of 52‐week data from CLEAR , a r and omized , double‐blind , phase 3b study . Results : Among 676 r and omized subjects , secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90 % improvement in Psoriasis Area and Severity Index ( PASI 90 ) ( 76 % vs 61 % [ P < .0001 ] ) ; PASI 100 responses were 46 % versus 36 % ( P = .0103 ) and Investigator 's Global Assessment responses of clear/almost clear skin were 80 % versus 65 % ( P < .0001 ) . Subjects on secukinumab  reported greater reductions in psoriasis‐related pain , itching , and scaling , and greater improvement across all quality ‐of‐life measures evaluated ( Dermatology Life Quality Index [ DLQI ] , EuroQoL 5‐Dimension Health Question naire , Work Productivity and Activity Impairment Question naire‐Psoriasis , and Health Assessment Question naire‐Disability Index ) . At week 52 , 72 % of subjects on secukinumab versus 59 % on ustekinumab ( P = .0008 ) reported no impact of skin disease on their lives ( DLQI 0/1 response ) . Safety and tolerability was comparable . Limitations : There was no placebo arm . Conclusion : In this head‐to‐head , double‐blind study , secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52 , greater improvement in quality of life , and a favorable and comparable safety profile BACKGROUND Currently available treatments for moderate to severe psoriasis are either incompletely effective in some patients , or are associated with toxic effects . Since tumour necrosis factor alpha ( TNF-alpha ) is thought to have a role in the pathogenesis of psoriasis , we did a double-blind , r and omised trial to assess the clinical benefit and safety of infliximab-a monoclonal antibody against TNF-alpha . METHODS 33 patients with moderate to severe plaque psoriasis were r and omly assigned intravenous placebo ( n=11 ) , infliximab 5 mg/kg ( n=11 ) , or infliximab 10 mg/kg ( n=11 ) at weeks 0 , 2 , and 6 . Patients were assessed at week 10 for the primary endpoint ( score on the physician 's global assessment [ PGA ] ) . Analysis was by intention to treat . FINDINGS Of the 33 patients enrolled , three dropped out . Nine of 11 ( 82 % ) patients in the infliximab 5 mg/kg group were responders ( good , excellent , or clear rating on PGA ) , compared with two of 11 ( 18 % ) in the placebo group ( difference 64 % [ 95 % CI 20 - 89 ] , p=0.0089 ) , and ten of 11 ( 91 % ) patients in the infliximab 10 mg/kg group were responders ( difference from placebo 73 % [ 30 - 94 ] , p=0.0019 ) . The median time to response was 4 weeks for patients in both infliximab groups . There were no serious adverse events , and infliximab was well tolerated . INTERPRETATION In this controlled trial , patients receiving the anti-TNF-alpha agent infliximab as monotherapy experienced a high degree of clinical benefit and rapid time to response in the treatment of moderate to severe plaque psoriasis compared with patients who received placebo . These findings suggest that TNF-alpha has a pivotal role in the pathogenesis of psoriasis BACKGROUND Apremilast , a small-molecule inhibitor of phosphodiesterase 4 , works intracellularly to modulate proinflammatory and anti-inflammatory mediator production , and doses of 20 mg twice daily have shown efficacy in the treatment of moderate to severe plaque psoriasis in a 12-week phase 2 study . We assessed the clinical efficacy and safety of different doses of apremilast in the treatment of patients with moderate to severe plaque psoriasis . METHODS In this phase 2b , multicentre , r and omised , placebo-controlled , dose-ranging study , patients ( aged ≥18 years ) with moderate to severe psoriasis were r and omly assigned ( in a 1:1:1:1 ratio ) to receive oral placebo or apremilast 10 , 20 , or 30 mg twice daily at 35 US and Canadian sites between Sept 24 , 2008 , and Oct 21 , 2009 . At week 16 , patients in the placebo group were assigned apremilast 20 or 30 mg twice daily until week 24 . R and omisation was generated with a permuted-block r and omisation list via interactive voice response system . For the first 16 weeks , treatment assignment was concealed from both investigators and participants . During weeks 16 - 24 , investigators and participants all knew that treatment was active , but the dose was concealed . The primary endpoint was the proportion of patients achieving at least 75 % reduction from baseline psoriasis area and severity index ( PASI-75 ) at week 16 . Analyses were by intention to treat ; missing values were imputed by last-observation-carried-forward . This trial is registered with Clinical Trials.gov , number NCT00773734 . FINDINGS 89 patients were r and omly assigned apremilast 10 mg , 87 apremilast 20 mg , and 88 apremilast 30 mg twice daily ; 88 were assigned placebo . At week 16 , PASI-75 was achieved in five patients ( 6 % ) assigned placebo , ten ( 11 % ) assigned apremilast 10 mg , 25 ( 29 % ) assigned 20 mg , and 36 ( 41 % ) assigned 30 mg . Apremilast 10 mg did not differ significantly  from  placebo in achievement of the endpoint ( odds ratio 2·10 ; 95 % CI 0·69 - 6·42 ) ; for both apremilast 20 mg ( 6·69 ; 2·43 - 18·5 ; p<0·0001 ) and apremilast 30 mg ( 11·5 ; 4·24 - 31·2 ; p<0·0001 ) , the differences from placebo were significant . Most adverse events ( 96 % ) were mild or moderate ; at least 5 % of patients had nausea , upper respiratory tract infection , diarrhoea , nasopharyngitis , headache , arthralgia ( placebo ) , gastroenteritis , or dyspepsia . Eight serious adverse events occurred ( three each , placebo and apremilast 20 mg ; two , apremilast 30 mg ) ; none were judged to be related to apremilast . Apremilast had no apparent effect on the results of haematological , urinalysis , immunological or inflammation , serum chemistry , or electrocardiographic tests . INTERPRETATION Apremilast , given orally at 20 or 30 mg twice daily , seems to be efficacious , safe , and tolerable for patients with moderate to severe plaque psoriasis . Our results support continuing , longer-term studies . FUNDING Celgene Corporation Background : Biologics targeting interleukin 17A ( IL‐17A ) allow for rapid clearance of psoriatic plaques , with a clinical ly favorable safety profile . Objectives : To compare the safety and efficacy of ixekizumab , an IL‐17A antagonist , with the safety and efficacy of the IL‐12/23 inhibitor ustekinumab through 52 weeks of treatment in the head‐to‐head trial IXORA‐S. Methods : Patients were r and omized to ixekizumab ( n = 136 ) or ustekinumab ( n = 166 ) and dosed per the approved labels . After 1 year , efficacy was assessed via improvements in Psoriasis Area and Severity Index ( PASI ) score ( with PASI 90 indicating a 90 % or greater improvement from baseline PASI score ) and a static Physician 's Global Assessment ( sPGA ) response of either 0 or 0 or 1 , with dropouts counted as nonresponders . Safety analyses included treatment‐emergent adverse events ( AEs ) . Results : At week 52 , significantly more ixekizumab‐treated patients ( P < .01 ) reported PASI 90 ( 104 [ 76.5 % ] ) , an sPGA response of 0 ( 72 [ 52.9 % ] ) , or an sPGA response of 0 or 1 ( 110 [ 82.1 % ] ) responses than did ustekinumab‐treated patients ( PASI 90 , 98 [ 59.0 % ] ; sPGA response of 0 , 60 [ 36.1 % ] ; and sPGA response of 0 or 1 , 108 [ 65.1 % ] ) . Treatment‐emergent AEs , serious AEs , and discontinuation rates were not different between the treatment groups . Injection site reactions occurred more frequently in the ixekizumab‐treated group ( ixekizumab , 22 [ 16.3 % ] ; ustekinumab , 2 [ 1.2 % ] ) ( P < .001 ) . Limitations : This study was not design ed to compare safety end points related to rare events . Conclusions : Compared with ustekinumab , ixekizumab showed superior efficacy and comparable safety outcomes through 52 weeks of treatment Fumaric acid esters ( FAEs ) are recommended in international guidelines for induction and long‐term treatment of adults with moderate‐to‐severe chronic plaque psoriasis . The fixed combination Fumaderm ® is approved in Germany , with dimethyl fumarate ( DMF ) being the main active ingredient
INTRODUCTION New generation biologics , including interleukin (IL)-17 and IL-23 inhibitors , have delivered higher rates of skin clearance than older treatments in head-to-head studies .
However , studies comparing these new biologics directly to one another are limited .
OBJECTIVES To compare the short-term efficacy of available ( or imminently available ) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis .