Biological treatments for moderate-to-severe psoriasis: indirect comparison. Efficacy and safety of secukinumab in the treatment of moderate‐to‐severe plaque psoriasis: a randomized, double‐blind, placebo‐controlled phase II dose‐ranging study Secukinumab induction and maintenance therapy in moderate‐to‐severe plaque psoriasis: a randomized, double‐blind, placebo‐controlled, phase II regimen‐finding study Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study Efficacy of adalimumab across subgroups of patients with moderate-to-severe chronic plaque psoriasis of the hands and/or feet: post hoc analysis of REACH Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo‐controlled dose‐ranging study Effects of the Tumor Necrosis Factor-&agr; Antagonist Adalimumab on Arterial Inflammation Assessed by Positron Emission Tomography in Patients With Psoriasis: Results of a Randomized Controlled Trial Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. 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 Effects of briakinumab treatment for moderate to severe psoriasis on health-related quality of life and work productivity and activity impairment: results from a randomized phase III study. Ustekinumab improves health-related quality of life in Korean and Taiwanese patients with moderate to severe psoriasis: results from the PEARL 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. Impact of ustekinumab on health-related quality of life in Japanese patients with moderate-to-severe plaque psoriasis: results from a randomized, double-blind, placebo-controlled phase 2 / 3 trial. Effect of adalimumab on sleep parameters in patients with psoriasis and obstructive sleep apnea: a randomized controlled trial Efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (LOTUS). A randomized controlled study of combination therapy with alefacept and narrow band UVB phototherapy (UVB) for moderate to severe psoriasis: efficacy, onset, and duration of response. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.
WHAT IS KNOWN AND OBJECTIVE Psoriasis is a chronic skin disease for which there is an increasing range of treatment options . Biological agents ( ustekinumab , adalimumab , infliximab and etanercept ) are indicated for moderate-to-severe plaque-type psoriasis in adults who fail to respond to , have a contraindication to , or are intolerant to other systemic therapies including cyclosporine , methotrexate and PUVA  Unfortunately , with new drugs , the pivotal trials leading to their licensing are often placebo-controlled trials rather than comparative trials vs. established therapies . Therefore , inference on comparative effectiveness of the newer agents must be derived indirectly , through estimation of effects of the new agents vs. a common comparator . The objective of this study is to compare the relative efficacy of the biological agents through a systematic review of the indirect clinical trial evidence . METHODS A systematic literature search was performed for clinical trials of biological agents in psoriasis . Pivotal , r and omized , double-blind , controlled ( placebo )  trials using intention-to-treat analysis were selected for detailed analysis . Trials must include PASI 75 as a primary end point . The indirect comparison was performed using the method of Bucher adjusted with the ITC calculator ( Indirect Treatment Comparisons of the Canadian Agency for Drugs and Technologies in Health ) , etanercept being the reference drug . We defined delta value for therapeutic equivalence as a difference in the efficacy of 25 % among the different treatment options . RESULTS AND DISCUSSION Fourteen studies ( four for ustekinumab , three for adalimumab , three for infliximab and four for etanercept ) were included . The indirect comparison results reveal that ustekinumab , adalimumab and infliximab were statistically superior to etanercept with an absolute risk difference for PASI 75 of 12 % ( 95 % CI = 5·9 - 18 % ) , 11 % ( 95 % CI = 5·3 - 16·7 % ) and 24 % ( 29·7 - 18·3 % ) respectively . However , in all situations , the 95 % confidence interval does not achieve clinical relevance as no delta exceeds the previously set value ( 25 % ) . WHAT IS NEW AND CONCLUSION Ustekinumab , adalimumab , infliximab and etanercept can be regarded as clinical equivalents for the treatment of psoriasis . Choice between these agents therefore depends on their relative safety profiles , individual contra-indications and cost effectiveness Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients , and although current biologic treatments are generally well tolerated , concerns exist with respect to long‐term safety . Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells , a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity Background Interleukin (IL)‐17A has major proinflammatory activity in psoriatic lesional skin Background Apremilast , a specific inhibitor of phosphodiesterase 4 , modulates pro-inflammatory and anti-inflammatory cytokine production . Objectives Apremilast ’s effect on patient-reported outcomes ( PROs ) in patients with moderate to severe psoriasis was evaluated in a phase IIb r and omized , controlled trial ( NCT00773734 ) . Methods In this 16-week , placebo-controlled study , 352 patients with moderate to severe plaque psoriasis received placebo or apremilast ( 10 , 20 , or 30 mg BID ) . PROs included Dermatology Life Quality Index ( DLQI ) , pruritus visual analog scale ( VAS ) , and Short-Form Health Survey ( SF-36 ) to assess health-related quality of life ( HRQOL ) . Changes from baseline and patients reporting improvements ≥minimum clinical ly important differences ( MCID ) were analyzed . Correlations between changes across various PRO instruments were explored . Results Baseline DLQI ( > 10 points ) and SF-36 MCS and domain scores indicated impairments in HRQOL . At 16 weeks , greater improvements from baseline in DLQI scores were reported with apremilast 20 ( −5.9 ) and 30 mg BID ( −4.4 ) compared with placebo ( 1.9 ; P≤0.005 for both ) , and a greater proportion of patients reported improvements ≥MCID ( 20 mg BID , 49.4 % , 30 mg BID , 44.3 % ) versus placebo ( 25.0 % ; P<0.04 ) . Greater improvements from baseline in pruritus VAS scores were reported with apremilast 20 ( −35.5 % ) and 30 mg BID ( −43.7 % ) versus placebo ( −6.1 % ; P≤0.005 ) . Significant and clinical ly meaningful improvements in SF-36 mental component summary scores ( P≤0.008 ) and Bodily Pain , Mental Health , and Role-Emotional domains were reported with all apremilast doses ( P<0.05 ) , and Social Functioning with 20 and 30 mg BID ( P<0.05 ) and Physical Functioning with 20 mg BID ( P<0.03 ) . Correlations between SF-36 scores and DLQI were moderate ( r>0.30 and ≤0.60 ) and low between SF-36 and pruritus VAS ( r≤0.30 ) , indicating they measure different aspects of the disease . Conclusions Apremilast treatment result ed in improved HRQOL , including DLQI and pruritus VAS over 16 weeks of treatment , in patients with moderate to severe psoriasis Background The R and omized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the H and s and Feet ( REACH ) trial demonstrated that adalimumab was efficacious and well-tolerated for the treatment of h and and /or foot psoriasis through 28 weeks . Objective To evaluate the effects of patient baseline characteristics on efficacy of adalimumab treatment of h and and /or foot psoriasis . Methods Patients with moderate-to-severe chronic plaque psoriasis of the h and s and /or feet were r and omized 2 : 1 to adalimumab or placebo during the 16 week , double-blind period of REACH . Primary endpoint was percentage of patients achieving Physician ’s Global Assessment of the h and s and /or feet of clear/almost clear at week 16 . Post hoc analyses evaluated effects of baseline patient characteristics on the primary endpoint . Patients with nail psoriasis at baseline were assessed for association of Nail Psoriasis Severity Index ( NAPSI ) 50 response with efficacy outcomes at week 16 . Results Seventy-two patients ( 49 adalimumab : 23 placebo )  were analysed . Greater percentages of adalimumab-treated patients achieved the primary endpoint vs. placebo across all subgroups . Among 31 patients with nail psoriasis , a greater percentage of adalimumab-treated patients achieved NAPSI 50 ( 56.5 % ) vs. placebo ( 12.5 % ) at week 16 . In adalimumab-treated patients , greater percentages of NAPSI 50 Responders vs. Non-responders achieved the primary endpoint , and had greater improvements in erythema , scaling , in duration and fissuring , Dermatology Life Quality Index , and pain scores . Conclusions Adalimumab was efficacious in treating chronic plaque psoriasis of the h and s and /or feet over 16 weeks , regardless of baseline characteristics . Marked improvement in nail psoriasis among adalimumab-treated patients correlated with significant improvements in skin disease and patient-reported outcomes This phase 2/3 , double-blind , placebo-controlled study was design ed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis . Overall , 158 patients were r and omized to receive ustekinumab 45 or 90 mg at weeks 0 , 4 , and every 12 weeks , or placebo with cross-over to ustekinumab at week 12 . The primary end-point was the proportion of patients achieving at least 75 % improvement in Psoriasis Area and Severity Index ( PASI 75 ) at week 12 . Physician 's Global Assessment ( PGA ) , Dermatology Life Quality Index ( DLQI ) , Nail Psoriasis Severity Index and joint pain Visual Analog Scale ( VAS ) were also measured . At week 12 , 59.4 % and 67.7 % of ustekinumab 45 and 90 mg patients achieved PASI 75 , respectively , compared with 6.5 % in the placebo group ( P < 0.0001 each ) . PASI 75 responses were maintained through week 64 in 65.0 % and 78.6 % of the ustekinumab-treated patients , respectively . Placebo cross-over patients had similar responses to ustekinumab-treated patients . Significant improvements in PGA , DLQI and VAS scores were observed at week 12 and generally maintained over time . Adverse events during the placebo-controlled period were similar among groups ( 45 mg , 65.6 % ; 90 mg , 59.7 % ; placebo , 65.6 % ) . Serious adverse events were observed in 0 % , 4.8 % and 6.3 % of patients , respectively . Through week 72 , similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg . Rates of injection site reactions and antibodies to ustekinumab were low . Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks . These results are consistent with those reported in the global , phase 3 studies Background  Etanercept plus methotrexate combination therapy  has not been adequately investigated in psoriasis AIMS CF101 demonstrated a marked anti-inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome . The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque-type psoriasis . MATERIAL S AND METHODS This was a phase 2 , multicentre , r and omized , double-blind , dose-ranging , placebo-controlled study . Seventy five patients with moderate to severe plaque-type psoriasis were enrolled , r and omized and treated with CF101 ( 1 , 2 , or 4 mg ) or placebo administered orally twice daily for 12 weeks . Safety and change from base line of Psoriasis Area and Severity Index ( PASI ) score and physician 's global assessment ( PGA ) score over 12 weeks . RESULTS In the 2 mg CF101-treated group , a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed , with a statistically significant difference on weeks 8 and 12 ( P = 0.047 ; P = 0.031 , respectively ) . In this group , 35.3 % of the patients achieved PASI ≥ 50 response , and 23.5 % of the patients achieved a PGA score of 0 or 1 . CF101 was safe and well tolerated . CONCLUSIONS CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis Background Tofacitinib is a novel , oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis Background —Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infa rct ion and stroke . Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation ; however , their effects on vascular inflammation are unknown . Methods and Results —This r and omized , controlled trial included 30 patients with moderate to severe psoriasis and a history , or multiple risk factors , of coronary atherosclerosis . Patients were r and omized ( 2:1 ) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment ( topical therapies or phototherapy ) .  Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15 , by 18F-fluorodeoxyglucose uptake on positron emission tomography . The change in target : background ratio in the vessel with highest baseline target : background ratio ( primary end point ) was significant at week 15 compared with baseline for patients r and omized to adalimumab ( –0.23 [ 95 % CI , –0.39 to –0.08 ] ; P=0.004 ) but not for the control group ( –0.10 [ 95 % CI , –0.32 to 0.12 ] ; P=0.35 ) . The difference between study arms for this primary end point did not reach statistical significance ( –0.13 [ 95 % CI , –0.01 to 0.14 ] ; P=0.32 ) . The change in target : background ratio at week 15 improved with adalimumab compared with controls both in the ascending aorta ( –0.26±0.11 , P=0.021 ) and in carotid arteries ( –0.32±0.15 , P=0.037 ) when analyzed separately ( secondary end points ) . Changes in other positron emission tomography indices also improved significantly with adalimumab compared with controls in the ascending aorta and carotids . High-sensitivity C-reactive protein decreased by 51 % at week 16 with adalimumab compared with 5 % in controls ( P=0·002 ) . Conclusions —The study did not meet its primary end point because the change in target : background ratio in patients r and omized to adalimumab was not different from controls . Although adalimumab may reduce vascular inflammation in patients with moderate to severe psoriasis , this effect is not large enough to be demonstrated in a study with a small sample size . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NTC00940862 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 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 Background Certolizumab pegol ( CZP ) is a PEGylated antitumour necrosis factor agent BACKGROUND Psoriasis is known to have a significant negative impact on a patient 's health-related quality of life , including social , recreational and work activities . OBJECTIVE To evaluate the effects of briakinumab on quality of life and work productivity measures in patients with moderate to severe psoriasis . METHODS Patients received either briakinumab ( n = 981 ) or placebo ( n = 484 ) during the 12-week induction phase of trial M06 - 890 . At week 12 , patients with a Physician 's Global Assessment score of ' Clear ' or ' Minimal ' entered the 40-week maintenance phase and were to receive briakinumab every 4 weeks , briakinumab every 12 weeks , or placebo . At weeks 12 and 52 , treatment groups were compared using mean change from baseline in health-related quality of life and Work Productivity and Activity Impairment Question naire scores and the percentage of patients with minimum clinical ly important differences . RESULTS At week 12 , more than half of the briakinumab-treated patients achieved improvements meeting or exceeding minimum clinical ly important differences for Dermatology Life Quality Index ( 75.9 % ) , and psoriasis- ( 64.8 % ) , and psoriatic arthritis-related ( 54.1 % ) pain scores ; 48.4 % achieved improvements for activity impairment . Although improvements in quality of life and work productivity measures were maintained at week 52 for both briakinumab regimens , responder rates were consistently greater in the every-4-week group than in the every-12-week group . CONCLUSION Briakinumab treatment result ed in clinical ly significant improvements in quality of life and work productivity in adults with moderate to severe psoriasis . Maintenance therapy was associated with a more pronounced benefit for the every-4-week briakinumab regimen BACKGROUND The PEARL study showed that the proportion of psoriasis patients achieving the primary endpoint ( at least 75 % improvement from baseline to week 12 in the Psoriasis Area and Severity Index ) was significantly higher in ustekinumab-treated patients compared with placebo . There is a paucity of data regarding the impact of psoriasis and its treatment on health-related quality of life ( HRQoL ) in Asian patients . OBJECTIVES To evaluate the effect of ustekinumab on HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis enrolled in the phase III , r and omized , double-blind , placebo-controlled PEARL study . METHODS In the PEARL study , 121 patients were r and omized to receive ustekinumab 45 mg at weeks 0 , 4 , and 16 ( n=61 ) or placebo at weeks 0 and 4 with crossover to ustekinumab at weeks 12 and 16 ( n=60 ) . A major secondary endpoint was the change in Dermatology Life Quality Index ( DLQI ) from baseline at week 12 . Other endpoints included the change in individual DLQI domains , proportion of patients achieving DLQI ≤ 1 ( no negative effect ) , and proportion of patients achieving ≥ 5-point reduction in DLQI ( clinical ly meaningful improvement ) at week 12 . RESULTS At baseline , psoriasis had a very large effect on HRQoL ( average DLQI , 15.7 ) . At week 12 , patients treated with ustekinumab 45 mg had significantly greater improvement from baseline in DLQI scores compared with placebo ( mean decrease , 11.2 vs 0.5 ( P<0.001 ) . Likewise , 32.2 % and 1.7 % of patients receiving ustekinumab 45 mg and placebo , respectively , achieved a DLQI ≤ 1 , and 81.4 % and 18.3 % achieved ≥ 5-point reduction ( both P<0.001 vs placebo ) . Individual DLQI domains in the ustekinumab group were significantly improved compared with placebo ( P<0.001 ) . For ustekinumab-r and omized patients , HRQoL improvements were sustained through week 28 . Placebo patients who crossed over to ustekinumab experienced similar improvements compared with those r and omized to ustekinumab . CONCLUSIONS Ustekinumab significantly improves HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis 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 This study evaluates the effect of ustekinumab on health-related quality of life ( HRQoL ) in Japanese patients with moderate-to-severe plaque psoriasis through 64 weeks . A total of 158 patients were r and omized to receive subcutaneous injections of ustekinumab 45 mg ( n = 64 ) or 90 mg ( n = 62 ) at weeks 0 , 4 , and every-12-weeks , or placebo ( n = 32 ) with crossover to ustekinumab at week 12 . Secondary study endpoints included change in Dermatology Life Quality Index ( DLQI ) at week 12 . Other assessment s included the 36-item Short Form health survey to assess Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores , and Psoriasis Disability Index ( PDI ) , a psoriasis-specific instrument to assess HRQoL. Baseline demographic and disease characteristics were similar across r and omized treatment groups . Ustekinumab-treated patients had significantly greater mean improvements in DLQI from baseline to week 12 ( 45 mg : 8.0 ± 6.5 ; 90 mg : 7.4 ± 6.5 ) than placebo-treated patients ( 0.3 ± 5.3 ; P < 0.0001 for each ) , and these improvements were maintained through week 64 . Also at week 12 , significant improvements from baseline in PDI scores were observed in ustekinumab-treated patients ( 45 mg : 8.6 ± 9.6 ; 90 mg : 12.0 ± 11.8 ) compared with placebo-treated patients ( -0.1 ± 4.2 ) . Improvements in the PCS ( 45 mg : 7.8 ± 14.5 ; 90 mg : 5.1 ± 12.0 ) and MCS ( 45 mg : 5.3 ± 9.8 ; 90 mg : 5.8 ± 10.5 ) scores were also observed in ustekinumab-treated patients at week 12 . Placebo-treated patients who crossed-over to ustekinumab achieved improvements in HRQoL comparable to those observed in patients originally r and omized to ustekinumab . Ustekinumab significantly improves HRQoL in Japanese patients with moderate-to-severe plaque psoriasis through week 64 Introduction :  Obstructive sleep apnea ( OSA )  is frequently seen in patients with psoriasis vulgaris . The effect of adalimumab , a TNF-α antagonist , on OSA is unknown . Methods : Patients with at least 5 % of their body surface area covered with psoriasis and a sleep apnea defined as an apnea/hypopnea index ( AHI ) of at least 15 were recruited . They were r and omized to either adalimumab 80 mg followed by adalimumab 40 mg every other week for 7 weeks or placebo . Patients were evaluated by polysomnography at baseline and day 56 . The objective of this trial was to study the efficacy of adalimumab on sleep parameters in patients with psoriasis and OSA . The primary end point of this double-blind study was the change in AHI between baseline and day 56 . Results : A total of 20 patients who were r and omized completed the trial . There was no significant difference ( p = 0.485 ) ( 95 % CI = –21.07–42.73 ) at day 56 in the change from baseline in AHI between groups . Conclusions : Adalimumab used for 8 weeks at 40 mg every other week for the treatment of psoriasis did not improve OSA in this 20-patient study BACKGROUND Available biologic agents for the treatment of psoriasis in China are limited . OBJECTIVES The LOTUS study is a phase 3 , double-blind , placebo-controlled study that evaluated the efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis . PATIENTS AND METHODS Patients ( n=322 ) were r and omized to receive ustekinumab 45 mg or placebo at weeks 0 and 4 , with placebo crossover to ustekinumab at week 12 ; all patients were followed up to week 36 . The primary end point was the proportion of patients achieving at least a 75 % improvement in the Psoriasis Area and Severity Index ( PASI 75 ) at week 12 . Other end points at week 12 included the proportion of patients with a Physician 's Global Assessment ( PGA ) score of 0 or 1 and the change in Dermatology Life Quality Index ( DLQI ) score from baseline . RESULTS At week 12 , 82.5 % of ustekinumab-treated patients achieved PASI 75 responses compared with 11.1 % of placebo-treated patients ( P<.001 ) . Clinical responses were maintained through week 28 , with maximum responses observed at week 24 . Significant improvements in PGA and DLQI were observed at week 12 and were generally maintained through week 28 . At week 12 , adverse events rates were similar between groups ( 45 mg : 42.5 % vs placebo : 38.5 % ) , and serious adverse events were reported in 0.6 % of patients in each group . Through week 36 , no cases of active tuberculosis , serious infections , malignancies , or major adverse cardiovascular events were reported . CONCLUSIONS Consistent with results previously reported in global phase 3 studies , ustekinumab was highly effective and generally well tolerated in Chinese patients with moderate to severe psoriasis through 36 weeks BACKGROUND Alefacept is an effective intermittent treatment for psoriasis that can provide long-lasting remissions . Combination therapy with narrow-b and ultraviolet B ( nbUVB ) phototherapy may enhance treatment outcomes and accelerate the onset of clinical response . OBJECTIVE To assess the efficacy of alefacept in combination with nbUVB phototherapy compared to alefacept alone in subjects with moderate to severe psoriasis . METHODS Ninety-eight adults with moderate to severe psoriasis were r and omized to treatment with alefacept 15 mg intramuscularly ( i.m . ) once weekly for 12 weeks alone or in combination with three times weekly nbUVB treatments in this prospect i ve , open-label , assessor-blinded , r and omized , multicenter , parallel-group , 36-week study . RESULTS A statistically significantly greater proportion of subjects in the alefacept plus nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to subjects in the alefacept alone arm ( 44.9 % vs 22.5 % , P=0.032 ) . Secondary outcomes were also in favor of the alefacept plus nbUVB group , including the proportion of subjects achieving a Physician Global Assessment ( PGA ) score of clear or almost clear at any time during the study ( 59.2 % vs 34.7 % , P=0.026 ) and reduction in percent body surface area ( BSA ) involved with psoriasis at week 16 ( 13.4 % vs 8.0 % , P<0.001 ) . The onset of clinical response was significantly faster in the combination therapy group compared to monotherapy ( mean time to PASI 75 : 82 vs 107 days , P=0.007 ) . Both treatments were generally well tolerated . LIMITATIONS Open-label , assessor-blinded study without a phototherapy-only treatment arm . CONCLUSION The addition of nbUVB to treatment with alefacept significantly enhanced and accelerated the clinical benefits of alefacept therapy and was generally safe and well-tolerated BACKGROUND Psoriasis is a chronic , inflammatory skin disease with a significant impact on health-related quality of life ( HRQoL ) . Tofacitinib ( CP-690,550 ) is a novel , oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator . OBJECTIVE This Phase 2b study assessed three tofacitinib dosage regimens vs. placebo to characterize the efficacy and safety of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis . We report the patient-reported outcome ( PRO ) data . METHODS A total of 197 patients were r and omized to tofacitinib 2 , 5 , 15 mg twice daily or placebo for 12 weeks . Six PRO question naires were completed during the study : Dermatology Life Quality Index , Itch Severity Score ( ISS ) , Short Form-36 question naire , version 2 ( SF-36 ) , Pain/Discomfort Assessment ( PDA ) , Patient Satisfaction with Study Medication ( PSSM ) item and Patient Global Assessment of psoriasis . RESULTS Treatment with tofacitinib result ed in significant , dose-dependent improvements in several PROs vs. placebo from week 2 onwards . At week 12 , least squares mean changes from baseline for Dermatology life quality index , ISS and SF-36 mental component scores were significantly greater for all active drug arms vs. placebo ( P < 0.05 ) , and significantly greater for tofacitinib 5 and 15 mg for SF-36 physical component scores vs. placebo ( P < 0.05 ) . At week 12 , all dose groups had significantly greater numbers of patients reporting ' Clear ' or ' Almost clear ' on the PtGA vs. placebo . CONCLUSION In patients with moderate-to-severe chronic plaque psoriasis , short-term ( 12-week ) treatment with oral twice-daily tofacitinib improves HRQoL outcomes and patient assessment of disease severity and symptoms , with an early onset noted 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 A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb briakinumab was efficacious in moderate-to-severe psoriasis .  A subsequent 52-week , double-blind , placebo-controlled phase III study evaluated induction and maintenance treatment . Patients were r and omized 2:1 to briakinumab ( 200 mg at weeks 0 and 4 and 100 mg at week 8) or placebo ; those with physician 's global assessment " clear " or " minimal " ( PGA " clear/minimal " ) at week 12 were then re-r and omized 2:2:1 to briakinumab 100 mg every 4 weeks ( q4-wk ) , every 12 weeks ( q12-wk ) , or to matching placebo to week 52 . Primary analyses conducted by nonresponder imputation compared proportions achieving PGA " clear/minimal " ( weeks 12 and 52 ) and ≥75 % improvement in psoriasis area and severity index ( PASI 75 ; week 12 ) . In all , 76.0 % of briakinumab vs. 4.3 % of placebo-treated patients achieved PGA " clear/minimal , " and 80.7 % vs. 4.5 % , respectively , achieved PASI 75 at week 12 ( P<0.001 each ) . At week 52 , 79.2 % of q4-wk-treated patients achieved PGA " clear/minimal " compared with 41.6 % and 6.0 % of q12-wk and placebo-treated patients , respectively ( P<0.001 for all treatment comparisons ) . Higher numbers of the following adverse events ( AEs ) of interest were observed with briakinumab during the placebo-controlled period , suggesting the need for surveillance for these events : serious infections ( five vs. one event with briakinumab vs. placebo , respectively ) , nonmelanoma skin cancers ( NMSCs ; four vs. zero squamous cell carcinomas ( SCCs ) ) , and major adverse cardiovascular events ( MACEs ; five vs. zero events ) BACKGROUND In this phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study , we assessed the efficacy and safety of brodalumab ( AMG 827 ) , a human anti-interleukin-17-receptor monoclonal antibody , for the treatment of moderate-to-severe plaque psoriasis . METHODS We r and omly assigned patients with a score of 12 or higher on the psoriasis area- and -severity index ( PASI , on which scores range from 0 to 72 , with higher scores indicating more severe disease ) and with 10 % or more of their body-surface area affected by psoriasis to receive brodalumab ( 70 mg , 140 mg , or 210 mg at day 1 and weeks 1 , 2 , 4 , 6 , 8 , and 10 or 280 mg monthly ) or placebo . The primary end point was the percentage improvement from baseline in the PASI score at week 12 . Secondary end points included improvement of at least 75 % and at least 90 % in the PASI score and the score on the static physician 's global assessment at week 12 . RESULTS A total of 198 patients underwent r and omization . At week 12 , the mean percentage improvements in the PASI score were 45.0 % among patients receiving 70 mg of brodalumab , 85.9 % among those receiving 140 mg , 86.3 % among those receiving 210 mg , 76.0 % among those receiving 280 mg , and 16.0 % among those receiving placebo ( P<0.001 for all comparisons with placebo ) . An improvement of at least 75 % and at least 90 % in the PASI score at week 12 was seen in 77 % and 72 % , respectively , of the patients in the 140-mg brodalumab group and in 82 % and 75 % , respectively , of the patients in the 210-mg group , as compared with 0 % in the placebo group ( P<0.001 for all comparisons ) . The percentage of patients with a static physician 's global assessment of clear or minimal disease was 26 % , 85 % , 80 % , and 69 % with the 70-mg , 140-mg , 210-mg , and 280-mg doses , respectively , of brodalumab , as compared with 3 % with placebo ( P<0.01 for all comparisons with placebo ) . Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group . The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis ( 8 % ) , upper respiratory tract infection ( 8 % ) , and injection-site erythema ( 6 % ) . CONCLUSIONS Brodalumab significantly improved plaque psoriasis in this 12-week , phase 2 study . ( Funded by Amgen ; Clinical Trials.gov number , NCT00975637 . ) BACKGROUND Type 17 helper T cells have been suggested to play a pathological role in psoriasis . They secrete several proinflammatory cytokines , including interleukin-17A ( also known as interleukin-17 ) . We evaluated the safety and efficacy of ixekizumab ( LY2439821 ) , a humanized anti-interleukin-17 monoclonal antibody , for psoriasis treatment . METHODS In our phase 2 , double-blind , placebo-controlled trial , we r and omly assigned 142 patients with chronic moderate-to-severe plaque psoriasis to receive subcutaneous injections of 10 , 25 , 75 , or 150 mg of ixekizumab or placebo at 0 , 2 , 4 , 8 , 12 , and 16 weeks . The primary end point was the proportion of patients with reduction in the psoriasis area- and -severity index ( PASI ) score by at least 75 % at 12 weeks . Secondary end points included the proportion of patients with reduction in the PASI score by at least 90 % or by 100 % . RESULTS At 12 weeks , the percentage of patients with a reduction in the PASI score by at least 75 % was significantly greater with ixekizumab ( except with the lowest , 10-mg dose)--150 mg ( 82.1 % ) , 75 mg ( 82.8 % ) , and 25 mg (76.7%)--than with placebo ( 7.7 % , P<0.001 for each comparison ) , as was the percentage of patients with a reduction in the PASI score by at least 90 % : 150 mg ( 71.4 % ) , 75 mg ( 58.6 % ) , and 25 mg ( 50.0 % ) versus placebo ( 0 % , P<0.001 for each comparison ) . Similarly , a 100 % reduction in the PASI score was achieved in significantly more patients in the 150-mg group ( 39.3 % ) and the 75-mg group ( 37.9 % ) than in the placebo group ( 0 % ) ( P<0.001 for both comparisons ) . Significant differences occurred at as early as 1 week and were sustained through 20 weeks . Adverse events occurred in 63 % of patients in both the combined ixekizumab groups and in the placebo group . No serious adverse events or major cardiovascular events were observed . CONCLUSIONS Use of a humanized anti-interleukin-17 monoclonal antibody , ixekizumab , improved the clinical symptoms of psoriasis . Further studies are needed to establish its long-term safety and efficacy in patients with psoriasis . ( Funded by Eli Lilly ; Clinical Trials.gov number , NCT01107457 . ) BACKGROUND Psoriasis significantly impairs work productivity and daily activities . OBJECTIVES We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis . METHODS Data were from the first 16 weeks of the R and omized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL ( REVEAL ) . Outcomes as measured by the Work Productivity and Activity Impairment Question naire for Psoriasis ( WPAI-Psoriasis ) included employment status , total work productivity impairment , and total activity impairment . Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response ( ≥ 75 % improvement in Psoriasis Area and Severity Index responders ) on WPAI-Psoriasis outcomes . Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity . RESULTS Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo ( 15.5 and 11.1 percentage points , respectively ; P < .001 ) . Unemployment rate , total work productivity impairment , and total activity impairment were significantly associated with greater baseline psoriasis severity . Changes in WPAI outcomes were significantly correlated with greater psoriasis severity . The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures ( Psoriasis Area and Severity Index and Physician Global Assessment ) . LIMITATIONS REVEAL only included WPAI data for 16 weeks . Therefore , long-term impact of adalimumab treatment on productivity outcomes could not be assessed . In addition , information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis . CONCLUSIONS Adalimumab reduced psoriasis-related  work productivity and activity impairment in patients with moderate to severe psoriasis
Background The treatment of psoriasis has evolved over the years , with the focus now largely on the use of biologic agents .
With treatment options exp and ing , evidence -based studies to guide physicians ’ treatment decisions become increasingly important .
Objective Our objective was to review current literature to provide an evidence -based up date on systemic therapies for psoriasis .