Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. Incidence and risk factors for psoriasis in the general population. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study. Treatment of Psoriatic Arthritis with Tumor Necrosis Factor Inhibitors: Longer-term Outcomes Including Enthesitis and Dactylitis with Golimumab Treatment in the Longterm Extension of a Randomized, Placebo-controlled Study (GO-REVEAL) The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial Treating Psoriasis with Etanercept in Italian Clinical Practice Dose-creep of Infliximab during psoriasis treatment: an observational study. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. Efficacy and safety of adalimumab across subgroups of patients with moderate to severe psoriasis. Effectiveness of adalimumab dose escalation, combination therapy of adalimumab with methotrexate, or both in patients with psoriasis in daily practice The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept A randomized, 'head-to-head' pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB-UVB) phototherapy in obese psoriasis patients. Two-year efficacy and safety of infliximab treatment in patients with active psoriatic arthritis: findings of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes. Adalimumab plus narrowband ultraviolet B light phototherapy for the treatment of moderate to severe psoriasis. A randomized study comparing the combination of nbUVB and etanercept to etanercept monotherapy in patients with psoriasis who do not exhibit an excellent response after 12 weeks of etanercept 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) A randomized, open-label trial of continuous versus interrupted etanercept therapy in the treatment of psoriasis. Adalimumab for moderate to severe chronic plaque psoriasis: efficacy and safety of retreatment and disease recurrence following withdrawal from therapy A phase IIIb, multicentre, randomized, double‐blind, vehicle‐controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. Long-term outcomes of interruption and retreatment vs. continuous therapy with adalimumab for psoriasis: subanalysis of REVEAL and the open-label extension study. Etanercept for the treatment of psoriasis in the elderly. Effect of 1-year anti-TNF-α therapy on aortic stiffness, carotid atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled study.
OBJECTIVE To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept , 50 mg twice weekly . DESIGN , SETTING , AND PATIENTS A phase 3 , r and omized , double-blind trial with an open-label extension . A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23 , 2003 , through June 22 , 2005 . INTERVENTIONS Patients were r and omized to receive  placebo or etanercept for 12 weeks . Beginning with week 13 , all patients ( N=591 ) received etanercept . MAIN OUTCOME MEASURES Exposure-adjusted adverse event rates were calculated . Efficacy measures included efficacy and patient global assessment of psoriasis . RESULTS Exposure-adjusted rates of adverse events , serious adverse events , infections , and serious infections were similar for placebo and etanercept treatments . Nonneutralizing antibodies to etanercept , observed in 18.3 % of patients , had no apparent effect on safety or efficacy . Patients responded within 2 weeks to etanercept , with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12 . At week 24 , after 12 weeks of open-label etanercept treatment , patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group . As both groups progressed through the open-label period , the Psoriasis Area and Severity Index response peaked at week 48 . At week 96 , 51.6 % of the original placebo-treated patients and 51.1 % of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75 % . CONCLUSIONS Extended exposure to 50 mg of etanercept twice weekly result ed in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo . Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy . Trial Registration clinical trials.gov Identifier NCT00111449 Objective Evaluate ustekinumab , an anti-interleukin (IL)-12 and IL-23 antibody , effects on radiographic progression in psoriatic arthritis ( PsA ) . Methods We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3 , r and omised , controlled trials . Patients had active PsA despite prior conventional and /or biologic disease-modifying antirheumatic drugs ( ≥5/66 swollen , ≥5/68 tender joints , C-reactive protein ≥3.0 mg/L , documented plaque psoriasis ) . Patients ( PSUMMIT-1 , n=615 ; PSUMMIT-2 , n=312 ) were r and omised  to ustekinumab 45 mg , 90 mg , or placebo , at weeks ( wk ) 0 , 4 and every ( q ) 12 wks . At wk 16 , patients with < 5 % improvement in tender/swollen joint counts entered blinded early escape . All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28 , then q 12 wks . Radiographs of h and s/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp ( vdH-S ) scores ; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis . Treatment effects were assessed using analysis of variance on van der Waerden normal scores ( factors = treatment , baseline methotrexate usage , and study ) . Results Integrated data analysis results indicated that ustekinumab-treated patients ( regardless of dose ) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients ( wk 0–24 total vdH-S score mean changes : 0.4-combined/individual ustekinumab dose groups , 1.0-placebo ; all p<0.02 ) . From wk 24 to wk 52 , inhibition of radiographic progression was maintained for ustekinumab-treated patients , and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 ( wk 24 – wk 52 , total vdH-S score mean change : 0.08 ) . Conclusions Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active 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 OBJECTIVES To study the clinical spectrum of psoriasis and the incidence in the general population and to identify risk factors associated with the occurrence of psoriasis . DESIGN Prospect i ve cohort study with nested case-control analysis . SETTING The data source was the United Kingdom General Practice Research Data base containing computerized clinical information entered by general practitioners ( GPs ) . PATIENTS The study population comprised patients receiving a first-ever diagnosis of psoriasis between January 1 , 1996 , and December 31 , 1997 , and free of cancer . INTERVENTIONS Diagnosis of psoriasis was vali date d in a r and om sample of 14 % of all ascertained cases requesting confirmation by the GPs . Nested case-control analysis included 3994 cases of psoriasis and a r and om sample of 10 000 controls frequency matched to cases by age , sex , and calendar year . MAIN OUTCOME MEASURES Incidence rate of psoriasis and estimates of the odds ratio ( OR ) and 95 % confidence interval ( CI ) for psoriasis as associated with selected risk factors . RESULTS The incidence rate of psoriasis was 14 per 10 000 person-years . Patients with antecedents of skin disorders and skin infection within the last year carried the highest risk of developing psoriasis ( OR , 3.6 [ 95 % CI , 3.2 - 4.1 ] , and OR , 2.1 [ 95 % CI , 1.8 - 2.4 ] , respectively ) . Also , smoking was found to be an independent risk factors for psoriasis ( OR , 1.4 [ 95 % CI , 1.3 - 1.6 ] ) . We did not find an association between risk of psoriasis and antecedents of stress , diabetes , hypertension , hyperlipidemia , cardiovascular disease , or rheumatoid arthritis . CONCLUSIONS The incidence rate in our study was higher than those published in other studies , probably owing to our case definition that considered cases recorded by the GPs independently of a specialist confirmation . Our results confirm the association between psoriasis , skin disorders , and smoking OBJECTIVES To evaluate further in a phase III , double blind trial the efficacy of infliximab in patients with active psoriatic arthritis ( PsA ) , as observed in the smaller IMPACT trial . METHODS 200 patients with active PsA unresponsive to previous treatment were r and omised to infusions of infliximab 5 mg/kg or placebo at weeks 0 , 2 , 6 , 14 , and 22 . Patients with inadequate response entered early escape at week 16 . The primary measure of clinical response was ACR20 . Other measures included Psoriatic Arthritis Response Criteria ( PsARC ) , Psoriasis Area and Severity Index ( PASI ) , and dactylitis and enthesopathy assessment s. RESULTS At week 14 , 58 % of patients receiving infliximab and 11 % of those receiving placebo achieved an ACR20 response and 77 % of infliximab patients and 27 % of placebo patients achieved PsARC ( both p<0.001 ) . Among the 85 % of patients with at least 3 % body surface area psoriasis involvement at baseline , 53/83 ( 64 % ) patients receiving infliximab had at least 75 % improvement in PASI compared with 2/87 ( 2 % ) patients receiving placebo at week 14 ( p<0.001 ) . These therapeutic effects were maintained through the last evaluation ( week 24 ) . Fewer infliximab patients than placebo patients had dactylitis at week 14 ( 18 % v 30 % ; p = 0.025 ) and week 24 ( 12 % v 34 % ; p<0.001 ) . Fewer infliximab patients ( 22 % ) than placebo patients ( 34 % ) had active enthesopathy at week 14 ( p = 0.016 ) ; corresponding figures at week 24 were 20 % and 37 % ( p = 0.002 ) . Infliximab was generally well tolerated , with a similar incidence of adverse events in each group . CONCLUSIONS Infliximab 5 mg/kg through 24 weeks significantly improved active PsA , including dactylitis and enthesopathy , and associated psoriasis BACKGROUND In two previous phase 3 studies , up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated . OBJECTIVE To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis . METHODS A total of 912 patients received 50 mg subcutaneous etanercept once weekly ( OW ) for the first 12 weeks of this extension study . Thereafter , eligible patients could maintain the 50 mg QW dose ( n = 321 ) or escalate to 50 mg twice weekly ( BIW ; n = 591 ) anytime thereafter based on one of three predetermined criteria . RESULTS Etanercept was well tolerated during 1056 patient-years of exposure ; no difference was observed between the 50 mg QW and 50 mg BIW dosages in rates of adverse events and infections . Improvement in skin disease was maintained throughout the study . Patients who stopped and then restarted etanercept also showed improvement in psoriasis . CONCLUSION Psoriatic patients continued to benefit from open-label etanercept treatment , both continuous and interrupted therapy , which was generally well tolerated after a combined 2.5 years of experience Objective . To assess longer-term outcomes , including enthesitis and dactylitis , in patients with active psoriatic arthritis ( PsA ) , in a study of golimumab treatment . Methods . Adult patients with active PsA were r and omized to receive subcutaneous injections of placebo ( n = 113 ) , golimumab 50 mg ( n = 146 ) , or golimumab 100 mg ( n = 146 ) every 4 weeks through Week 20 . All patients received golimumab 50 mg or 100 mg from Week 24 onward . Entheses tenderness was scored in 15 body sites using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score ( MASES ) . Dactylitis was assessed in 20 digits of the h and s and feet . Results . Among the 405 r and omized patients , 77 % presented with enthesitis and 34 % dactylitis at baseline . At Week 24 of the placebo-controlled study phase , significant differences were observed between golimumab 50 mg and /or 100 mg and placebo for mean percent improvement in the PsA-modified MASES [ 46 % ( p < 0.001 ) and 52 % ( p < 0.001 ) vs 13 % , respectively ] and the dactylitis score [ 66 % ( p = 0.09 ) and 82 % ( p < 0.001 ) vs 28 % , respectively ] . By Week 52 , improvements were maintained among patients r and omized to receive golimumab ( mean improvements of 54 % for PsA-modified MASES and 77 % for the dactylitis score ) . Those given placebo who had enthesitis or dactylitis at baseline and who crossed over to golimumab at Week 16 or 24 had somewhat less improvement at Week 52 ( i.e. , 39 % for the PsA-modified MASES , 57 % for dactylitis score ) . Conclusion . Treatment of PsA patients with the TNF inhibitor golimumab was effective across all components of disease , including enthesitis and dactylitis , and efficacy was maintained over longer-term followup Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy . This pilot study , with a small patient population , was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis and inadequate response to methotrexate . Out patients with plaque psoriasis ( Psoriasis Area and Severity Index > or = 8 and /or body surface area > 10 % ) , despite methotrexate treatment ( > or = 3 months ; > or = 7.5 mg/week ) were r and omized to either etanercept with metho nottrexate tapered and discontinued ( n = 28 ) or  etanercept with continuous methotrexate ( n = 31 ) . Significantly more patients had a Physicians ' Global Assessment of " clear"/"almost clear " in the combination group compared with etanercept/methotrexate taper ( 66.7 vs. 37.0 % , respectively ; p = 0.025 ) . Adverse events were similar for both groups , with no cases of tuberculosis , malignancies or opportunistic infections reported . Addition of etanercept to methotrexate achieved significant improvement in psoriasis after 24 weeks OBJECTIVE Clinical and radiographic responses were evaluated in patients with psoriatic arthritis ( PsA ) treated for up to 2 years with etanercept .  METHODS Patients were previously r and omized to receive placebo or etanercept  in a double-blind study and chose to participate in the current open-label extension phase . All patients received etanercept 25 mg twice weekly . Radiographic progression was determined at baseline , 1 year , and 2 years using the Sharp method modified to include joints frequently affected in PsA. Arthritis and psoriasis responses were determined using American College of Rheumatology 20 % ( ACR20 ) improvement criteria , PsA response criteria ( PsARC ) , and the psoriasis area severity index ( PASI ) . RESULTS Of 205 patients r and omized , 169 entered open-label , and 141 [ 71 r and omized to receive placebo ( placebo/etanercept ) and 70 r and omized to receive etanercept ( etanercept/etanercept ) ]  had radiographic data available for analysis at 2 years . ACR20 criteria , PsARC , and PASI 50 criteria were met by 64 % , 84 % , and 62 % , respectively , of etanercept/etanercept patients at the end of the 48-week open-label period . Placebo/etanercept patients achieved comparable results within 12 weeks that were sustained at 48 weeks ( 63 % , 80 % , and 73 % ) . Radiographic progression was inhibited in the etanercept/ etanercept patients ( mean adjusted change in total Sharp score of -0.38 from baseline to 2 yrs ) . In placebo/etanercept patients , disease progression was inhibited once patients began receiving etanercept ( mean adjusted change of -0.22 from 1 year to 2 years ) . Adverse event rates were similar to those observed during r and omized phase , with only one serious adverse event deemed possibly related to etanercept . CONCLUSION These data demonstrate a sustained benefit of etanercept treatment , including inhibition of radiographic progression , in patients with OBJECTIVE Adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody , was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis ( PsA ) . METHODS Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were r and omized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks . Study visits were at baseline , weeks 2 and 4 , and every 4 weeks thereafter . The primary efficacy end points were the American College of Rheumatology 20 % improvement ( ACR20 ) response at week 12 and the change in the modified total Sharp score of structural damage at week 24 . Secondary end points were measures of joint disease , disability , and quality of life in all patients , as well as the severity of skin disease in those patients with psoriasis involving at least 3 % of body surface area . RESULTS At week 12 , 58 % of the adalimumab-treated patients ( 87 of 151 ) achieved an ACR20 response , compared with 14 % of the placebo-treated patients ( 23 of 162 ) ( P < 0.001 ) . At week 24 , similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo ( P < 0.001 ) . Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index ( PASI ) , 59 % achieved a 75 % PASI improvement response at 24 weeks , compared with 1 % of the 69 placebo-treated patients evaluated ( P < 0.001 ) . Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo . Adalimumab was generally safe and well-tolerated . CONCLUSION Adalimumab significantly improved joint and skin manifestations , inhibited structural changes on radiographs , lessened disability due to joint damage , and improved quality of life in patients with moderately to severely active Background  Etanercept plus methotrexate combination therapy  has not been adequately investigated in psoriasis Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy . To evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue , we performed a prospect i ve single-centre study with infliximab therapy combined with stable methotrexate therapy .  Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab ( 3 mg/kg ) at baseline , and at weeks 2 , 6 , 14 and 22 in an open-label study . In addition , patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week . Clinical assessment s , including Psoriasis Area and Severity Index ( PASI ) and Disease Activity Score ( DAS ) , were performed at baseline and every 2 weeks afterward . In addition , skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4 . Immunohistochemical analysis was performed to detect the number of blood vessels , the expression of adhesion molecules and the presence of vascular growth factors . Stained sections were evaluated by digital image analysis . At week 16 , the mean PASI was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 ( P ≤ 0.02 ) . The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 ( P ≤ 0.02 ) . We found some fluctuations in DAS response as compared with the change in PASI , with the latter exhibiting a steady decrease over time . After 4 weeks the cell infiltrate was reduced in both skin and synovium . There was a significant reduction in the number of blood vessels in dermis and synovium at week 4 . A significant reduction in the expression of αvβ3 integrin , a marker of neovascularization , was also found in both skin and synovium at week 4 . In addition , a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4 . We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium . In conclusion , low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium , result ing in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis Objectives To compare the efficacy over 12 weeks of two different etanercept regimens in treating the skin manifestations of psoriasis in patients who also have psoriatic arthritis and to evaluate efficacy and safety over an additional 12 weeks of open label etanercept treatment . Design R and omised double blind multicentre outpatient study . Setting 98 outpatient facilities in Europe , Latin America , and the Asia Pacific region . Participants 752 patients with both psoriasis ( evaluated by dermatologists ) and psoriatic arthritis ( evaluated by rheumatologists ) . Interventions During the blinded portion of the study , participants were r and omised to receive etanercept 50 mg twice weekly ( n=379 ) or 50 mg once weekly ( n=373 ) for 12 weeks by subcutaneous injection . All participants then received open label etanercept 50 mg once weekly for 12 additional weeks , while remaining blinded to the regimen . Main outcome measures The primary efficacy end point was the proportion of participants achieving “ clear ” or “ almost clear ” on the physician ’s global assessment of psoriasis at week 12 . Secondary efficacy analyses included psoriasis area and severity index , American College of Rheumatology responses , psoriatic arthritis response criteria , and improvement in joint and tendon disease manifestations . Results At week 12 , 46 % ( 176/379 ) of participants receiving etanercept 50 mg twice weekly achieved a physician ’s global assessment of psoriasis of “ clear ” or “ almost clear ” compared with 32 % ( 119/373 ) in the group treated with 50 mg once weekly ( P<0.001 ) . In contrast , an equally high percentage of participants in both groups achieved psoriatic arthritis response criteria ( 77 % ( 284/371 ) in the twice weekly/once weekly group versus 76 % ( 282/371 ) in the once weekly/once weekly group ) . Participants treated with 50 mg twice weekly/once weekly had greater mean reductions from baseline in the psoriasis area and severity index at week 12 compared with those who received 50 mg once weekly/once weekly ( 71 % v 62 % , P<0.001 ) , with less difference at week 24 ( 78 % v 74 % , P<0.110 ) . Joint and tendon disease manifestations improved from baseline in both groups to a similar extent . No new safety signals were seen in either etanercept treatment group , and no significant difference in the safety profiles was observed . Conclusions In participants with active psoriasis and psoriatic arthritis , initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than with 50 mg once weekly . A regimen of 50 mg once weekly seems to be appropriate for treatment of joint and tendon rheumatic symptoms . The choice of regimen should be determined by the clinical needs of the individual patient . Trial registration Clinical trials NCT00245960 Abstract Background : Conventional antipsoriatic therapies are often administered until remission , with treatment resumed in the case of relapse , in order to reduce the likelihood of cumulative , dose-dependent toxicities . Biological agents have been safely used in continuous therapy . Objective : To assess the use of etanercept for psoriasis in clinical practice in Italy . Methods : This was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis ( with a Psoriasis Area and Severity Index [ PASI ] score ≥10 ) treated with etanercept . The study comprised a treatment and subsequent discontinuation period . Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008 . Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction ≥50 % ( PASI50 ) and a PASI score < 10 at the end of treatment . Etanercept treatment was restarted if the PASI score reached ≥10 or the patient had a clinical relapse . Data were collected retrospectively up to June 2008 and prospect ively between July 2008 and January 2009 . Patients received etanercept during the treatment period , followed by no etanercept treatment ( other psoriasis treatment permitted ) during the discontinuation period , and etanercept again during re-treatment . The main outcome measures were : PASI scores ( type A responders : PASI reduction ≥75 % [ PASI75 ] ; type B responders : PASI50 and PASI final score < 10 ) , Dermatology Life Quality Index ( DLQI ) scores and body surface area ( BSA ) involvement . Time from discontinuation to retreatment was evaluated . Use of other antipsoriatic medications was recorded throughout . Results : Eighty-five patients were evaluable for the treatment period . Overall , 55 ( 64.7 % ) of these patients were prescribed etanercept 50 mg twice weekly . The mean treatment duration was approximately 25 weeks . In total , 79 patients ( 92.9 % ) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis . Overall , 68/85 ( 80 % ) were type A responders . During the treatment period , 7/85 ( 8.2 % ) patients received other antipsoriatic therapies . Improvements in mean DLQI score ( −71.5 % ) and mean BSA involvement ( −79.2 % ) were also observed . Etanercept was well tolerated . During the discontinuation period , 40/77 ( 51.9 % ) patients used other antipsoriatic medications ( group 1 ) and 37/77 ( 48.1 % ) did not ( group 2 ) . The mean duration of discontinuation was significantly longer in group 1 ( 174 days ) than in group 2 ( 117 days , log-rank test : p = 0.0013 ) . Conclusion : In clinical practice , the duration of discontinuation from etanercept was in accordance with previously reported data , and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not . High rates of PASI50 and PASI75 response were obtained with etanercept , and these rates were higher than those observed in controlled clinical studies . Etanercept treatment was flexible , effective and well tolerated , and was associated with improved quality of life Infliximab ( Remicade ® ) is a chimeric monoclonal antibody that binds to the proinflammatory cytokine , tumour necrosis factor-α ( TNF-α ) , and neutralizes its biologic activity . Data generated from r and omized controlled trials document the efficacy and safety of infliximab for short-term treatment ( up to 1 year ) ( 1 , 2 ) . The efficacy of infliximab also seems to be maintained for longer periods of time , as we documented in a 5-year observational study ( 3 ) . Infliximab showed the highest patient retention rate among the three anti-TNF-α agents included in the analysis ( the others being etanercept and adalimumab ) and the most frequent cause of treatment termination was loss of clinical efficacy . This result contrasted with the review of the data from the clinical trials ( 4 ) , in which drug survival was highest for etanercept , followed by adalimumab and infliximab . One of the explanations of the significantly higher patient retention to infliximab in our data -set could be the flexibility in the adjustment of the dose and the intervals between drug infusions . Infliximab is the only TNF-α antagonist that is dosed by weight , and international expert opinion encourages optimization of the treatment by either decreasing the intervals between infusions ( e.g. from every 8 weeks to every 6 weeks ) or increasing the dose of drug administered ( 5 ) . In this retrospective study , we were able to confirm the hypothesis that the mean dose of infliximab is often adjusted upwards during the course of therapy and many patients require the dosage to exceed the recommended 5 mg/kg every 8 weeks 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 The phase III r and omized controlled evaluation of adalimumab every other week dosing in moderate to severe psoriasis trial ( REVEAL ) demonstrated adalimumab induced significant improvements and was well tolerated for patients with moderate to severe psoriasis . OBJECTIVE We sought to determine the efficacy and safety of adalimumab for various subgroups of patients in REVEAL with moderate to severe psoriasis and to determine whether these profiles were consistent with the overall results . METHODS Patients ( N = 1212 ) with moderate to severe psoriasis were r and omized to adalimumab or placebo during the first 16 weeks of the trial . The primary efficacy endpoint was percentage of patients achieving at least 75 % improvement in the Psoriasis Area and Severity Index ( PASI ) score at week 16 . Post hoc subgroup analyses were conducted to determine relationships between adalimumab efficacy and /or safety and age group , sex , race , baseline weight intervals , baseline body mass index , disease duration , baseline severity , prior treatments , and comorbidities . RESULTS Consistent 75 % or greater improvement in the PASI score responses were observed across all patient subgroups , with moderately reduced responses noted for patients in the greater weight and body mass index categories . A multivariate analysis identified treatment received , weight , and age as the most influential factors for mean percentage change in PASI score at week 16 . No significant differences in the risk of serious adverse events in adalimumab- versus placebo-treated patients were observed across weight categories or for patients with baseline comorbidities . LIMITATIONS These subanalyses are limited by their relatively short , 16-week duration . CONCLUSION Treatment of moderate to severe psoriasis with adalimumab led to consistent 75 % or greater improvement in PASI score response rates across the majority of patient subgroups , with no significant differences in serious adverse events Background : To increase effectiveness of st and ard adalimumab treatment 40 mg every other week ( EOW ) for patients with psoriasis , dose escalation to 40 mg every week or addition of methotrexate ( MTX ) are possible strategies . Methods : Daily practice data about adalimumab treatment were extracted from a prospect i ve observational cohort . We analyzed all patients with insufficient efficacy of adalimumab EOW who received 1 ) adalimumab dose escalation , 2 ) addition of MTX to adalimumab EOW , or 3 ) both .  Effectiveness was analyzed after 12 and 24 weeks using PASI50 , PASI75 , and mean differences in PASI . Results : Forty-seven treatment episodes ( TE ) of adalimumab dose escalations , 11 of MTX addition and six combinations were analyzed . After a first episode of adalimumab dose escalation , 25 % and 35 % achieved PASI50 after 12 and 24 weeks , respectively . After MTX introduction to adalimumab EOW , 9 % and 18 % achieved PASI50 after 12 and 24 weeks , respectively . No related serious adverse events were reported . Conclusions : Twenty-five percent of first TE with adalimumab dose escalation induced a PASI50 response after 12 weeks and 35 % after 24 weeks . Addition of MTX to adalimumab EOW result ed in PASI50 in 9 % after 12 weeks and 18 % after 24 weeks . Defining patient-groups that will benefit from these interventions is important Objective The aim of this study was to test the hypothesis that the reason for non-response ( caused by immunogenicity or not ) to a first tumour necrosis factor ( TNF ) inhibitor defines whether a second TNF inhibitor will be effective . Methods This cohort study consisted of 292 consecutive patients with rheumatoid arthritis ( RA ) , all treated with etanercept .  A total of 89 patients ( 30 % ) were treated previously with infliximab or adalimumab ( ‘ switchers ’ ) , and the remaining 203 ( 70 % ) were anti-TNF naive . All switchers were divided into two groups : with and without antibodies against the previous biological . Differences in clinical response to etanercept between switchers with and without antibodies and patients who were anti-TNF naive were assessed after 28 weeks of treatment using changes in Disease Activity Score in 28 joints ( DAS28 ) . Results After 28 weeks of treatment , response to etanercept  did not differ between patients who were anti-TNF naive and switchers with anti-drug antibodies ( ΔDAS28=2.1±1.3 vs ΔDAS28=2.0±1.3 ; p=0.743 ) . In contrast , switchers without anti-drug antibodies had a diminished response to etanercept treatment compared to patients who were TNF naive ( ΔDAS28=1.2±1.3 vs ΔDAS28=2.1±1.3 ; p=0.001 ) and switchers with antibodies ( ΔDAS28=1.2±1.3 vs ΔDAS28=2.0±1.3 ; p=0.017 ) . Conclusion Patients with RA with an immunogenic response against a first TNF-blocking agent had a better clinical response to a subsequent TNF blocker compared to patients with RA without anti-drug antibodies . Hence , determining immunogenicity can be helpful in deciding in which patient switching could be beneficial and can be part of a personalised treatment regimen BACKGROUND Etanercept is a tumour necrosis factor-alpha antagonist used for the treatment of moderate-to-severe psoriasis . Current opinion suggests that etanercept may have reduced efficacy in obese patients . Narrowb and ultraviolet B ( NB-UVB ) phototherapy is unaffected by body weight and the addition of NB-UVB to etanercept therapy may supplement the efficacy of etanercept in these patients . OBJECTIVE To evaluate the efficacy and safety of NB-UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate-to-severe plaque psoriasis . METHODS Thirty psoriasis patients with a body mass index ( BMI ) greater than 30 were enrolled into this r and omized , ' head-to-head ' comparison study . All subjects received 50 mg of etanercept twice weekly for 12 weeks and then r and omized to receive either etanercept monotherapy or combination etanercept and NB-UVB three times weekly for an additional 12 weeks . Treatment response was evaluated using Psoriasis Area and Severity Index ( PASI ) , body surface area ( BSA ) and Physician 's Global Assessment ( PGA ) scores . RESULTS Twenty-five subjects completed the study . At 12 weeks , 48 % of all patients achieved PASI 75 . By Week 24 , 62.5 % of all patients achieved PASI 75 . Patients in the etanercept monotherapy and combination etanercept and NB-UVB phototherapy arms had similar rates of achieving PASI 75 ( 46.7 % vs. 53.3 % of each group , respectively ) . CONCLUSION Combination etanercept and NB-UVB has similar efficacy to etanercept monotherapy in obese patients . This result indicates that even in the setting of obesity , the majority of patients respond well to etanercept , with or without NB-UVB OBJECTIVE To investigate longterm efficacy/safety of infliximab over 2 years in patients with active psoriatic arthritis ( PsA ) . METHODS Initially , 104 patients were r and omized to receive blinded infusions of infliximab 5 mg/kg or placebo at Weeks 0 , 2 , 6 , and 14 . At Week 16 , all patients received infliximab 5 mg/kg every 8 weeks through Week 46 . Seventy-eight of the 87 patients completing the first year continued into the open-label longterm extension and received infliximab 5 mg/kg at Weeks 54 , 62 , 70 , 78 , 86 , and 94 . The primary efficacy endpoint for the study extension was the proportion of patients with at least 20 % improvement in the American College of Rheumatology response criteria ( ACR20 ) at Week 98 . Radiographic progression was assessed by the PsA-modified van der Heijde-Sharp score in patients with radiographs available at baseline and Week 98 ( n = 43 ) . RESULTS At Week 98 , 62 % ( 48/78 ) of infliximab-treated patients achieved an ACR20 response ; 45 % ( 35/78 ) and 35 % ( 27/78 ) of patients achieved ACR50 and ACR70 responses , respectively . Among patients with baseline Psoriasis Area and Severity Index scores > or= 2.5 , 64 % ( 16/25 ) achieved > 75 % improvement from baseline to Week 98 . The average estimated annual radiographic progression with infliximab treatment was significantly reduced versus the estimated baseline rate of progression . No new safety issues were observed during the second year of the study . CONCLUSION Therapy with infliximab 5 mg/kg through Week 94 produced sustained improvement in joint and skin symptoms , inhibited radiographic progression , and continued to exhibit a favorable benefit-risk ratio in this population with treatment-refractory BACKGROUND Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder . Etanercept and narrow-b and ultraviolet light B ( NB-UVB ) are widely used to treat this disease . OBJECTIVE To evaluate the effectiveness , tolerability , and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis . METHODS This 12-week , single-arm , open-label study evaluated the combination of etanercept 50 mg twice weekly and NB-UVB thrice weekly in 86 patients . The primary outcome measure was > or = 75 % improvement from baseline in the Psoriasis Area and Severity Index ( PASI 75 ) . Other measures included PASI 90 , PASI 100 , and the Dermatology Life Quality Index ( DLQI ) . RESULTS At week 12 , 26.0 % achieved PASI 100 , 58.1 % achieved PASI 90 , and 84.9 % of patients achieved PASI 75 . Mean improvement from baseline in DLQI was 84.4 % . No unexpected , untoward adverse events were noted . CONCLUSIONS A 12-week course of etanercept plus NB-UVB phototherapy was well tolerated and produced clinical ly meaningful improvements in signs and symptoms of moderate to severe plaque psoriasis and in patient-reported outcomes . Further investigation of the safety and efficacy of the use of such combination for this indication in controlled clinical trials would be of interest BACKGROUND Combining systemic agents with phototherapy is becoming a st and ard of care for patients with moderate to severe psoriasis . The combination of adalimumab and phototherapy has not been previously explored . METHODS In this 24-week single-arm open-label study , adults with moderate to severe psoriasis received adalimumab 40 mg every other week and narrowb and (NB)-UVB phototherapy three times a week for 12 weeks and then were followed for 12 weeks without treatment . Response to therapy was determined using the Psoriasis Area and Severity Index ( PASI ) , Body Surface Area ( BSA ) affected and Physician 's Global Assessment ( PGA ) of psoriasis . RESULTS Twenty patients were enrolled with mean baseline scores of 17.0 for PASI , 21.2 for BSA and 3.5 for PGA . Half ( 10/20 ) of the patients achieved PASI 75 response by week 4 . At the end of treatment at week 12 , 19 ( 95 % ) patients achieved PASI-75 , 15 ( 75 % ) patients achieved PASI-90 and 11 ( 55 % ) patients achieved PASI-100 . Seventeen ( 85 % ) patients were clear or almost clear ( PGA score = 1 ) . Mean baseline PASI , BSA and PGA scores improved by 95 percent , 93 percent and 80 percent , respectively . Disease improvement was observed through the end of follow up period at week 24 . No serious adverse events were noted . CONCLUSION Concurrent use of adalimumab and NB-UVB phototherapy was clinical ly effective and well tolerated in patients with moderate to severe psoriasis . This combination regimen represents a new treatment option for clinical practice and warrants further investigation in controlled clinical trials Abstract Background : There is a lack of data on the combination of phototherapy with etanercept in patients who have not shown an excellent response to etanercept monotherapy . Objectives : To study the combination of narrow-b and ultraviolet B ( nbUVB ) phototherapy with etanercept in patients not demonstrating an improvement of 90 % in their Psoriasis Area Severity Index ( PASI-90 ) after 12 weeks of etanercept .  Patients and methods : Psoriatic patients not reaching PASI-90 after 12 weeks of etanercept therapy were r and omized ( 1:1 ) to receive either etanercept ( 50 mg once a week ) monotherapy or in combination with nbUVB three times weekly for periods of 4 weeks . Results : Seventy-five patients were r and omized . Only 21.6 % of patients achieved adherence of 80 % or more for nbUVB treatments . At week 24 , PASI-90 was reached by 16.2 % of patients in the etanercept plus nbUVB group when compared with 15.8 % of patients in the etanercept monotherapy group ( p = 1.000 ) . In patients with high adherence to nbUVB , the PASI-90 at week 16 was 42.9 % for etanercept with nbUVB when compared with 3.4 % for etanercept monotherapy ( p = 0.018 ) . Both treatments were well tolerated . Conclusion : Addition of nbUVB after 12 weeks of etanercept did not significantly improve the clinical response except for a subset of patients with high adherence to nbUVB . Clinical Trials Registration number : NCT00640393 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 Although etanercept is used as a continuous therapy for moderate to severe plaque psoriasis , intermittent use may be necessary in some instances . OBJECTIVE In this r and omized , open-label study , we evaluated the effectiveness and safety of continuous versus interrupted etanercept therapy . METHODS All patients received uninterrupted etanercept 50 mg twice weekly during the first 12 weeks , followed by either continuous ( n = 1272 ) or interrupted ( n = 1274 ) etanercept 50 mg once weekly in the next 12 weeks . The primary effectiveness end point was the proportion of responders ( those who achieved a Physician 's Global Assessment [ PGA ] score < or=2 and improvement from baseline ) at week 24 . Secondary end points included the PGA " clear/almost clear " status , the PGA Scalp Psoriasis score , and the Dermatology Life Quality Index . A modified intent-to-treat analysis was performed . RESULTS At week 12 , comparable high proportions of responders were reported in the continuous ( 71.3 % ) and interrupted ( 72.0 % ) arms . However , the proportion of responders at week 24 was greater in the continuous group than in the interrupted group ( 71.0 % vs 59.5 % ; P < .0001 ) . Similar results were observed in secondary end points . The mean number of etanercept doses ( 1 dose = 50 mg ) received by patients in the continuous group was 33.4 , compared with 28.0 in the interrupted group . Etanercept was well tolerated in both treatment arms . LIMITATIONS We examined one round of discontinuation and re-treatment ; interrupted therapy provided less total medication to responding patients . CONCLUSIONS Continuous and interrupted etanercept therapy was effective and generally well tolerated in patients with psoriasis , with greater improvements observed in the continuous arm at week 24 . Most patients regained their response after reinitiation of etanercept Background Adalimumab is effective for moderate to severe chronic plaque psoriasis ; however , data regarding retreatment following withdrawal and subsequent relapse are limited Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis BACKGROUND Patients with psoriasis tend to be overweight , and the efficacy of fixed-dose biologics may be compromised by high body weight . OBJECTIVE We sought to determine whether the optimal dose of ustekinumab is affected by weight in patients with psoriasis . METHODS Patients were r and omized in two phase III trials ( PHOENIX 1 and 2 ) to receive 45 mg or 90 mg of ustekinumab every 12 weeks ( n = 1331 ) or placebo with crossover to ustekinumab at week 12 ( n = 665 ) . Efficacy and serum ustekinumab concentrations were to be evaluated by 10-kg increments of body weight at week 28 ( steady-state trough level ) . RESULTS Mean baseline weight was 93.9 and 91.0 kg in PHOENIX 1 and 2 , respectively . Based on the analyses by 10-kg increments , a cutoff of 100 kg was determined to best differentiate the dose response . The proportion of patients with at least 75 % improvement from baseline in Psoriasis Area and Severity Index score was 74.2 % for 90 mg and 54.6 % for 45 mg in heavier patients ( > 100 kg ) , but the proportion with a response of at least 75 % improvement from baseline in Psoriasis Area and Severity Index score was similar between doses ( 80.8 % vs 76.9 % ) in lighter patients ( ≤ 100 kg ) . Serum ustekinumab concentrations were also affected by weight , with lower serum concentrations observed in heavier patients at each dose . Safety was not affected by weight . LIMITATIONS Low numbers of patients at the extremes of body weight may limit the analyses of these subgroups . CONCLUSION Results of weight-based analyses of clinical and pharmacokinetic data indicate that fixed dosing of ustekinumab based on weight is appropriate for the treatment of patients with psoriasis BACKGROUND Many patients with psoriasis develop psoriatic arthritis , a chronic inflammatory disease that afflicts peripheral synovial , axial , and entheseal structures . The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis . We did a r and omised , placebo-controlled , phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis . METHODS In this phase 3 , multicentre , double-blind , placebo-controlled trial at 104 sites in Europe , North America , and Asia-Pacific , adults with active psoriatic arthritis ( ≥5 tender and ≥5 swollen joints , C-reactive protein ≥3·0 mg/L ) were r and omly assigned ( 1:1:1 , by dynamic central r and omisation based on an algorithm implemented by an interactive voice-web response system ) to 45 mg ustekinumab , 90 mg ustekinumab , or placebo at week 0 , week 4 , and every 12 weeks thereafter . At week 16 , patients with less than 5 % improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab ( if in the placebo group ) or 90 mg ustekinumab ( if in the 45 mg group ) . At week 24 , all remaining patients in the placebo group received ustekinumab 45 mg , which they continued at week 28 and every 12 weeks thereafter . Our primary endpoint was 20 % or greater improvement in American College of Rheumatology ( ACR20 ) criteria at week 24 . This trial is registered with Clinical Trials.gov ( NCT01009086 ) and EudraCT ( 2009 - 012264 - 14 ) . FINDINGS Between Nov 30 , 2009 , and March 30 , 2011 , 615 patients were r and omly assigned-206 to placebo , 205 to 45 mg ustekinumab , and 204 to 90 mg ustekinumab . More ustekinumab-treated ( 87 of 205 [ 42·4 % ] in the 45 mg group and 101 of 204 [ 49·5 % ] in the 90 mg group ) than placebo-treated ( 47 of 206 [ 22·8 % ] ) patients achieved ACR20 at week 24 ( p<0·0001 for both comparisons ) ; responses were maintained at week 52 . At week 16 , proportions of patients with adverse events were similar in the ustekinumab and placebo groups ( 171 of 409 [ 41·8 % ] vs 86 of 205 [ 42·0 % ] ) . INTERPRETATION Ustekinumab significantly improved active psoriatic arthritis compared with placebo , and might offer an alternative therapeutic mechanism of action to approved biological treatments . FUNDING Janssen Research & Development OBJECTIVE To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis ( PsA ) . METHODS One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug ( DMARD ) had failed were recruited into this investigator-initiated , multicenter , r and omized , double-blind , placebo-controlled clinical trial . During the initial blinded portion of the study , patients received infusions of infliximab ( 5 mg/kg ) or placebo at weeks 0 , 2 , 6 , and 14 . After week 16 , patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50 , while patients initially r and omized to infliximab continued to receive active treatment at the same dose through week 50 . The primary efficacy outcome was achievement of the American College of Rheumatology 20 % criteria for improvement in rheumatoid arthritis ( ACR20 ) at week 16 . Additional predefined clinical efficacy assessment s included the Psoriasis Area and Severity Index ( PASI ) score , the ACR50 and ACR70 criteria , the Disease Activity Score in 28 joints , the Health Assessment Question naire , ratings of enthesitis and dactylitis , and the Psoriatic Arthritis Response Criteria score . RESULTS The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 ( 65 % ) was significantly higher than the proportion of placebo-treated patients who achieved this response ( 10 % ) . In addition , 46 % of infliximab-treated patients achieved an ACR50 response , and 29 % achieved an ACR70 response ; no placebo-treated patient achieved these end points . Among patients who had PASI scores of > /=2.5 at baseline , 68 % of infliximab-treated patients achieved improvement of > /=75 % in the PASI score at week 16 compared with none of the placebo-treated patients . Continued therapy with infliximab result ed in sustained improvement in articular and dermatologic manifestations of PsA through week 50 . The incidence of adverse events was similar between the treatment groups . CONCLUSION Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis , psoriasis , dactylitis , and enthesitis in patients with active PsA that had been resistant to DMARD therapy . With continued infliximab treatment , benefits were sustained through 50 weeks . The benefit-to-risk ratio appeared favorable in this study population BACKGROUND Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor , a key proinflammatory cytokine involved in the pathogenesis of psoriasis . OBJECTIVE We sought to evaluate clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapy . METHODS We conducted a 52-week , multicenter study of 1212 patients r and omized to receive adalimumab ( 40 mg ) or placebo every other week for the first 15 weeks . At least 75 % improvement in the Psoriasis Area and Severity Index ( PASI ) score was the criterion for advancement through this multiphase study . RESULTS At week 16 , 71 % ( 578 of 814 ) of adalimumab- and 7 % ( 26 of 398 ) of placebo-treated patients achieved greater than or equal to 75 % improvement in the PASI score . During weeks 33 to 52 , the percentage of patients rer and omized to placebo who lost adequate response ( defined as < 50 % improvement in the PASI response relative to baseline and at least a 6-point increase in PASI score from week 33 ) was 28 % compared with 5 % of patients treated continuously with adalimumab . LIMITATIONS Lack of an active comparator and evaluation of maintenance of response beyond week 52 are limitations . CONCLUSION Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis . TRIAL REGISTRATION Clinical trials.gov . NCT00237887 BACKGROUND REVEAL was a 52-week study of adalimumab for moderate to severe psoriasis . At Week 33 ,  adalimumab-treated patients with sustained responses ( PASI ≥75 at Weeks 16 and 33 ) were re-r and omized to receive adalimumab or placebo . Subsequently , they could receive adalimumab in an open-label extension ( OLE ) study . OBJECTIVE To compare long-term efficacy and safety of adalimumab 40 mg every other week ( eow ) , given as continuous treatment or with one period of interruption followed by retreatment . METHODS Patients who were re-r and omized to adalimumab or placebo at REVEAL Week 33 and received ≥ 1 dose of OLE adalimumab  were analysed as the continuous and retreatment groups , respectively , for > 2 years of OLE treatment with adalimumab 40 mg eow . LOCF was used for missing efficacy data . RESULTS At OLE Weeks 0 , 12 and 24 , PASI 75 response rates were 84 % , 84 % , 86 % with continuous treatment ( N = 233 ) vs. 45 % , 71 % , 79 % with retreatment ( N = 227 ) . Thereafter , efficacies were slightly greater for continuous treatment but similar between groups , with PASI 75 response rates at OLE Week 108 of 75 % vs. 73 % respectively . Retreatment was most effective for patients with ≥ PASI 50 responses when retreatment was initiated . Adverse event rates for retreatment were equal to or lower than those for continuous treatment . CONCLUSIONS In psoriasis patients with sustained PASI 75 responses  to adalimumab , long-term efficacy of retreatment after a ≤ 19-week interruption was similar to efficacy achieved with > 3 years continuous treatment . Adalimumab retreatment provided the best results when initiated before responses had declined below PASI 50 This study 's objective was to analyze the effect of etanercept on Psoriasis Area and Severity Index ( PASI ) 50 , PASI 75 , and Dermatology Life Quality Index in geriatric and nongeriatric population s. We conducted a post hoc analysis of two large phase III r and omized placebo trials of etanercept . There were no statistically significant differences between the elderly and young with regard to the number of patients reaching a PASI 50 or PASI 75 at any of the 3 dosing regimens . Baseline Dermatology Life Quality Index scores were not statistically significant between both groups and both the elderly and young had similar changes in Dermatology Life Quality Index with therapy . A limitation of the study was the small number of patients in the elderly group . In conclusion , psoriasis and its treatment has a similar impact on quality of life in the elderly as it does in the young BACKGROUND Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis ( RA ) , ankylosing spondylitis ( AS ) and psoriatic arthritis ( PsA ) . The proinflammatory protein calprotectin is associated with inflammatory arthropathies , vascular pathology , and acute coronary events . We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness ( CIMT ) in patients with inflammatory arthropathies , and the relationships to the levels of calprotectin . METHODS Fifty-five patients with RA , AS , or PsA and a clinical indication for anti-TNF-α therapy  were included and followed with regular examinations for 1 year . Thirty-six patients starting with anti-TNF-α therapy  were compared with a nontreatment group of 19 patients . Examinations included assessment s of aortic stiffness ( aortic pulse wave velocity , aPWV ) , CIMT , and plasma calprotectin . RESULTS After 1 year , aPWV ( mean ( s.d . ) ) was improved in the treatment group , but not in the control group ( -0.54 [ 0.79 ] m/s vs. 0.06 [ 0.61 ] m/s , respectively ; P = 0.004 ) , and CIMT progression ( median ( quartile cut-points , 25th and 75th percentiles ) ) was reduced in the treatment group compared to the control group ( -0.002 [ -0.038 , 0.030 ] mm vs. 0.030 [ 0.011 , 0.043 ] mm , respectively ; P = 0.01 ) . In multivariable analyses , anti-TNF-α therapy over time was associated with improved aPWV ( P = 0.02 ) and reduced CIMT progression ( P = 0.04 ) , and calprotectin was longitudinally associated with aPWV ( P = 0.02 ) . CONCLUSIONS Long-term anti-TNF-α therapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies . Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients
INTRODUCTION AND OBJECTIVES A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available .
However , applying the evidence in numerous clinical scenarios has engendered debate ; under these circumstances , the consensus of experts is useful .