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: BACKGROUND Patients and the course of treatment in daily practice are different from r and omized controlled trials ( RCTs ) . OBJECTIVES PRIMARY OBJECTIVE to analyse the percentage of patients achieving PASI 75 .  SECONDARY OBJECTIVES PASI 50 , PASI 90 , PASI 100 responses , the percentage of patients experiencing at least one serious adverse event ( SAE ) and the response in biologic-naïve vs. non-naïve patients . METHODS Prospect ively collected efficacy and safety data of a cohort of psoriasis patients treated with adalimumab in daily practice between May 2007 and July 2011 were analyzed . Efficacy was determined using an intention-to-treat analysis and an as treated analysis , in comparison with the course baseline PASI before the start of adalimumab and the original baseline PASI before the start of any biologic therapy . RESULTS Eighty-five patients received adalimumab therapy with a mean treatment duration of 1.4 ( range 0.02 - 3.1 ) years . Compared with the original baseline PASI , PASI 75 response rates at week 12 and 24 were 34 % and 38 % ( ITT ) . PASI 75 responses were well maintained until week 132 . Only the PASI 75 response rate at week 12 differed significantly between biologic-naïve ( 56 % ) and non-naïve patients ( 29 % ) . Sixteen patients ( 19 % ) experienced 28 SAEs . Seven patients ( 8 % ) experienced SAEs considered possibly or probably related to adalimumab . CONCLUSIONS In this cohort , PASI75 responses were substantial but lower than in RCTs and other daily practice studies . Efficacy was well maintained during more than 2 years of follow-up and differed only between biologic-naïve and non-naïve patients at week 12 . The incidence of SAEs was low but seems higher than observed in RCTs Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment 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 . OBJECTIVE To describe the use of systemic therapy for psoriasis  ( biologic and nonbiologic [ classic ] drugs ) in patients not adequately represented in r and omized controlled trials ( RCTs ) and the risk of serious adverse events ( SAEs ) in these patients . DESIGN A registry inception cohort was used . SETTING Thirteen dermatology departments in Spain participated . PATIENTS A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy  were evaluated . A total of 1042 patients ( 2179 person-years ) were included . EXPOSURE Inadequate representation in trials was defined as the presence of any of the following factors : elderly age ( > 70 years ) ; type of psoriasis other than chronic plaque psoriasis ; history of infection caused by hepatitis B , hepatitis C , or human immunodeficiency virus ; history of cancer ( excluding nonmelanoma skin cancer ) ; and chronic renal or hepatic disease . MAIN OUTCOME MEASURES Serious adverse events as defined by the International Conference on Harmonization were evaluated . RESULTS In all , 29.8 % of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs . These individuals had an increased risk of SAEs ( incidence rate ratio , 2.7 ; 95 % CI , 1.5 - 4.7 ) . Patients exposed to biologics had an adjusted increased risk of SAEs ( incidence rate ratio , 2.3 ; 95 % CI , 1.1 - 4.8 ) that was similar in patients eligible and ineligible for RCTs . CONCLUSIONS Patients ineligible for RCTs are an important proportion ( 30 % ) of those receiving systemic therapy for psoriasis . These patients have a higher risk of SAEs and should be closely monitored . Patients exposed to biologics ( whether these patients are eligible for RCTs or ineligible ) are susceptible to the same increase in risk of SAEs , but biologics add to a higher baseline risk in patients who are ineligible for RCTs . The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients BACKGROUND Interleukin-17A is considered to be central to the pathogenesis of psoriasis . We evaluated secukinumab , a fully human anti-interleukin-17A monoclonal antibody , in patients with moderate-to-severe plaque psoriasis . METHODS In two phase 3 , double-blind , 52-week trials , ERASURE ( Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis ) and FIXTURE ( Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis ) , we r and omly assigned 738 patients ( in the ERASURE study ) and 1306 patients ( in the FIXTURE study ) to subcutaneous secukinumab at a dose of 300 mg or 150 mg ( administered once weekly for 5 weeks , then every 4 weeks ) , placebo , or ( in the FIXTURE study only ) etanercept at a dose of 50 mg ( administered twice weekly for 12 weeks , then once weekly ) . The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75 % or more from baseline in the psoriasis area- and -severity index score ( PASI 75 ) and a score of 0 ( clear ) or 1 ( almost clear ) on a 5-point modified investigator 's global assessment ( co primary end points ) . RESULTS The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept : in the ERASURE study , the rates were 81.6 % with 300 mg of secukinumab , 71.6 % with 150 mg of secukinumab , and 4.5 % with placebo ; in the FIXTURE study , the rates were 77.1 % with 300 mg of secukinumab , 67.0 % with 150 mg of secukinumab , 44.0 % with etanercept , and 4.9 % with placebo ( P<0.001 for each secukinumab dose vs. comparators ) . The proportion of patients with a response of 0 or 1 on the modified investigator 's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept : in the ERASURE study , the rates were 65.3 % with 300 mg of secukinumab , 51.2 % with 150 mg of secukinumab , and 2.4 % with placebo ; in the FIXTURE study , the rates were 62.5 % with 300 mg of secukinumab , 51.1 % with 150 mg of secukinumab , 27.2 % with etanercept , and 2.8 % with placebo ( P<0.001 for each secukinumab dose vs. comparators ) . The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept . CONCLUSIONS Secukinumab was effective for psoriasis in two r and omized trials , validating interleukin-17A as a therapeutic target . ( Funded by Novartis Pharmaceuticals ; ERASURE and FIXTURE Clinical Trials.gov numbers , NCT01365455 and NCT01358578 , respectively . ) BACKGROUND A problem encountered when analyzing long-term efficacy is that the number of patients in follow-up decreases with time for different reasons . The method used to account for missing observations for the therapy under analysis has a great influence on the inference of efficacy . OBJECTIVE To describe the long-term efficacy of etanercept for psoriasis in daily practice using 3 analytical approaches . METHODS Prospect i ve data from a cohort of patients with psoriasis treated with etanercept for at least 24 weeks were analyzed using 3 analytical approaches : as treated analysis , intention-to-treat analysis ( ITT ) with last observation carried forward ( LOCF ) and intention-to-treat analysis with modified nonresponder imputation ( modified NRI ) . RESULTS One hundred thirty-one patients were treated with etanercept during 134 treatment episodes with a mean treatment duration of 2.7 years . The maximum follow-up was 6.0 years . The method ological approach chosen had a great influence . Psoriasis Area and Severity Index ( PASI ) 75 response rates varied from 60 % in the as-treated approach to 34 % in LOCF and to 29 % in modified NRI at week 264 . LIMITATIONS All analytical methods applied have limitations . Other outcome measures could be used to overcome the bias introduced by each method of analysis , such as drug survival . CONCLUSIONS The method ological approach chosen to analyze long-term efficacy data has a great influence on the inferences that may be drawn regarding the degree of efficacy . Therefore we support the use of different methods to present long-term efficacy data BACKGROUND : Psoriasis is a common , chronic , cell‐mediated , inflammatory skin disease . Treatment limitations and a developing underst and ing of its pathogenesis on a molecular level have encouraged much interest in the field of immunomodulatory therapy . OBJECTIVE : To evaluate the efficacy and safety of fumaric acid esters , in particular dimethylf 
    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: BACKGROUND Patients and the course of treatment in daily practice are different from r and omized controlled trials ( RCTs ) . OBJECTIVES PRIMARY OBJECTIVE to analyse the percentage of patients achieving PASI 75 .  SECONDARY OBJECTIVES PASI 50 , PASI 90 , PASI 100 responses , the percentage of patients experiencing at least one serious adverse event ( SAE ) and the response in biologic-naïve vs. non-naïve patients . METHODS Prospect ively collected efficacy and safety data of a cohort of psoriasis patients treated with adalimumab in daily practice between May 2007 and July 2011 were analyzed . Efficacy was determined using an intention-to-treat analysis and an as treated analysis , in comparison with the course baseline PASI before the start of adalimumab and the original baseline PASI before the start of any biologic therapy . RESULTS Eighty-five patients received adalimumab therapy with a mean treatment duration of 1.4 ( range 0.02 - 3.1 ) years . Compared with the original baseline PASI , PASI 75 response rates at week 12 and 24 were 34 % and 38 % ( ITT ) . PASI 75 responses were well maintained until week 132 . Only the PASI 75 response rate at week 12 differed significantly between biologic-naïve ( 56 % ) and non-naïve patients ( 29 % ) . Sixteen patients ( 19 % ) experienced 28 SAEs . Seven patients ( 8 % ) experienced SAEs considered possibly or probably related to adalimumab . CONCLUSIONS In this cohort , PASI75 responses were substantial but lower than in RCTs and other daily practice studies . Efficacy was well maintained during more than 2 years of follow-up and differed only between biologic-naïve and non-naïve patients at week 12 . The incidence of SAEs was low but seems higher than observed in RCTs Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment 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 . OBJECTIVE To describe the use of systemic therapy for psoriasis  ( biologic and nonbiologic [ classic ] drugs ) in patients not adequately represented in r and omized controlled trials ( RCTs ) and the risk of serious adverse events ( SAEs ) in these patients . DESIGN A registry inception cohort was used . SETTING Thirteen dermatology departments in Spain participated . PATIENTS A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy  were evaluated . A total of 1042 patients ( 2179 person-years ) were included . EXPOSURE Inadequate representation in trials was defined as the presence of any of the following factors : elderly age ( > 70 years ) ; type of psoriasis other than chronic plaque psoriasis ; history of infection caused by hepatitis B , hepatitis C , or human immunodeficiency virus ; history of cancer ( excluding nonmelanoma skin cancer ) ; and chronic renal or hepatic disease . MAIN OUTCOME MEASURES Serious adverse events as defined by the International Conference on Harmonization were evaluated . RESULTS In all , 29.8 % of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs . These individuals had an increased risk of SAEs ( incidence rate ratio , 2.7 ; 95 % CI , 1.5 - 4.7 ) . Patients exposed to biologics had an adjusted increased risk of SAEs ( incidence rate ratio , 2.3 ; 95 % CI , 1.1 - 4.8 ) that was similar in patients eligible and ineligible for RCTs . CONCLUSIONS Patients ineligible for RCTs are an important proportion ( 30 % ) of those receiving systemic therapy for psoriasis . These patients have a higher risk of SAEs and should be closely monitored . Patients exposed to biologics ( whether these patients are eligible for RCTs or ineligible ) are susceptible to the same increase in risk of SAEs , but biologics add to a higher baseline risk in patients who are ineligible for RCTs . The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients BACKGROUND Interleukin-17A is considered to be central to the pathogenesis of psoriasis . We evaluated secukinumab , a fully human anti-interleukin-17A monoclonal antibody , in patients with moderate-to-severe plaque psoriasis . METHODS In two phase 3 , double-blind , 52-week trials , ERASURE ( Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis ) and FIXTURE ( Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis ) , we r and omly assigned 738 patients ( in the ERASURE study ) and 1306 patients ( in the FIXTURE study ) to subcutaneous secukinumab at a dose of 300 mg or 150 mg ( administered once weekly for 5 weeks , then every 4 weeks ) , placebo , or ( in the FIXTURE study only ) etanercept at a dose of 50 mg ( administered twice weekly for 12 weeks , then once weekly ) . The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75 % or more from baseline in the psoriasis area- and -severity index score ( PASI 75 ) and a score of 0 ( clear ) or 1 ( almost clear ) on a 5-point modified investigator 's global assessment ( co primary end points ) . RESULTS The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept : in the ERASURE study , the rates were 81.6 % with 300 mg of secukinumab , 71.6 % with 150 mg of secukinumab , and 4.5 % with placebo ; in the FIXTURE study , the rates were 77.1 % with 300 mg of secukinumab , 67.0 % with 150 mg of secukinumab , 44.0 % with etanercept , and 4.9 % with placebo ( P<0.001 for each secukinumab dose vs. comparators ) . The proportion of patients with a response of 0 or 1 on the modified investigator 's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept : in the ERASURE study , the rates were 65.3 % with 300 mg of secukinumab , 51.2 % with 150 mg of secukinumab , and 2.4 % with placebo ; in the FIXTURE study , the rates were 62.5 % with 300 mg of secukinumab , 51.1 % with 150 mg of secukinumab , 27.2 % with etanercept , and 2.8 % with placebo ( P<0.001 for each secukinumab dose vs. comparators ) . The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept . CONCLUSIONS Secukinumab was effective for psoriasis in two r and omized trials , validating interleukin-17A as a therapeutic target . ( Funded by Novartis Pharmaceuticals ; ERASURE and FIXTURE Clinical Trials.gov numbers , NCT01365455 and NCT01358578 , respectively . ) BACKGROUND A problem encountered when analyzing long-term efficacy is that the number of patients in follow-up decreases with time for different reasons . The method used to account for missing observations for the therapy under analysis has a great influence on the inference of efficacy . OBJECTIVE To describe the long-term efficacy of etanercept for psoriasis in daily practice using 3 analytical approaches . METHODS Prospect i ve data from a cohort of patients with psoriasis treated with etanercept for at least 24 weeks were analyzed using 3 analytical approaches : as treated analysis , intention-to-treat analysis ( ITT ) with last observation carried forward ( LOCF ) and intention-to-treat analysis with modified nonresponder imputation ( modified NRI ) . RESULTS One hundred thirty-one patients were treated with etanercept during 134 treatment episodes with a mean treatment duration of 2.7 years . The maximum follow-up was 6.0 years . The method ological approach chosen had a great influence . Psoriasis Area and Severity Index ( PASI ) 75 response rates varied from 60 % in the as-treated approach to 34 % in LOCF and to 29 % in modified NRI at week 264 . LIMITATIONS All analytical methods applied have limitations . Other outcome measures could be used to overcome the bias introduced by each method of analysis , such as drug survival . CONCLUSIONS The method ological approach chosen to analyze long-term efficacy data has a great influence on the inferences that may be drawn regarding the degree of efficacy . Therefore we support the use of different methods to present long-term efficacy data BACKGROUND : Psoriasis is a common , chronic , cell‐mediated , inflammatory skin disease . Treatment limitations and a developing underst and ing of its pathogenesis on a molecular level have encouraged much interest in the field of immunomodulatory therapy . OBJECTIVE : To evaluate the efficacy and safety of fumaric acid esters , in particular dimethylf 
    Output:
    