human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    