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: Abstract Objective : To monitor the safety and efficacy profile of long-term treatment with diclofenac , nabumetone , meloxicam and celecoxib in patients with rheumatoid arthritis . Design and methods : This r and omised , prospect i ve clinical trial included a total of 461 subjects ( 313 females and 148 males ) with clinical ly diagnosed rheumatoid arthritis . Their average age was 46.9 ± 14.4 years ( range 20–69 years ) , and the average disease duration was 1333.7 ± 992.85 days . Subjects were r and omly assigned daily administration of one of the following : diclofenac 75–100 mg , meloxicam 15 mg , nabumetone l000 mg or celecoxib 200 mg . During the 6-month treatment period , a monthly patient interview was conducted to evaluate drug efficacy and safety . Results : 407 subjects successfully completed the 6-month treatment . Sixteen patients ( 12.2 % ) withdrew from the diclofenac group , 16 ( 12.2 % ) from the nabumetone group , 17 ( 11.8 % ) from the meloxicam group and five ( 9.1 % ) from the celecoxib group . Most withdrawals occurred during the first 3 months of treatment . Reasons for withdrawals in the first three groups were lack of efficacy ( 44.9 % ) and adverse effects ( 38.8 % ) . For the celecoxib group , high cost ( 80 % ) was the main reason for withdrawal . Adverse drug reactions to NSAIDs mostly occurred at an early stage of treatment , with an incidence rate of 31.9 % for the diclofenac group , 19.9 % for the nabumetone group , 25.2 % for the meloxicam group , and 7.27 % for the celecoxib group . Clinical efficacy rates for the four NSAIDs were positively related to the length of treatment . During the first 4 months , diclofenac , meloxicam and celecoxib showed better efficacy than nabumetone . There were no significant differences in efficacy during the fifth and sixth months . The overall 6-month effectiveness rates were 68.8 % for diclofenac , 59.8 % for nabumetone , 67.6 % for meloxicam and 69.1 % for celecoxib . Conclusions : Adverse drug reactions and their related withdrawals occurred mostly at an early stage of NSAID treatment , so it is crucial to strengthen pharmacovigilance during this period . Among the investigated NSAIDs , celecoxib did not prove to be superior to diclofenac , nabumetone or meloxicam with respect to its efficacy in the treatment of rheumatoid arthritis ; however , it did show good patient compliance and safety profiles BACKGROUND SKI306X , which consists of biologically active ingredients from Clematis m and sburica , Tricbosantbes kirilowii , and Prunella vulgaris , was developed and tested in pre clinical trials in Korea . Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect , and that it can delay the destruction of cartilage in rheumatoid arthritis ( RA ) . OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA . METHODS This study was a 6-week , multicenter , r and omized , double-blind , double-dummy , Phase III , noninferiority clinical trial . Eligible patients were aged 18 to 80 years , had a history of RA with a disease duration of > or =3 months , and were functional American College of Rheumatology ( ACR ) class I , II , or III before entry . After a washout period of 2 weeks , patients were r and omized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks . The primary end point was a change in patient assessment of pain intensity using a visual analog scale ( VAS ) . The secondary end points were a 20 % improvement in response rate as defined by the ACR ( ACR20 ) and the frequency of rescue medication use . Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups , and all patients were assessed for adverse events ( AEs ) , clinical laboratory data , and vital signs . AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator . RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and r and omized to 1 of 2 treatment groups . Ninety-one patients ( 10 male , 81 female ; mean [ SD ] age , 52.13 [ 12.64 ] years ; mean [ SD ] duration of RA , 9.08 [ 10.23 ] years ; no. [ % ] of ACR class I , II , and III , 13 [ 14.29 ] , 44 [ 48.35 ] and 34 [ 37.36 ] patients , respectively ) received SKI306X 200 mg TID and 92 patients ( 10 male , 82 female ; mean [ SD ] age , 51.78 [ 10.94 ] years ; mean [ SD ] duration of RA , 8.78 [ 7.78 ] years ; no. [ % ] of ACR class I , II , and III , 14 [ 15.22 ] , 44 [ 47.83 ] , and 34 [ 36.96 ] patients , respectively ) received celecoxib 200 mg BID . An analysis of the change in reported pain intensity as determined by VAS ( mm ) score between baseline and week 3 ( mean [ SD ] , 13.64 [ 16.62 ] vs 14.45 [ 15.89 ] ) , and between baseline and week 6 ( 18.4 [ 20.8 ] vs 17.9 [ 19.1 ] , respectively ) suggested that SKI306X was not inferior to celecoxib . The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 ( 16/87 [ 18.4 % ] vs 24/87 [ 27.6 % ] , respectively ) and at week 6 ( 29/87 [ 33.3 % ] vs 29/87 [ 33.3 % ] ) . The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 ( 54/87 [ 62.1 % ] vs 47/87 [ 54.0 % ] , respectively ) or week 6 ( 57/87 [ 65.5 % ] vs 49/87 [ 56.3 % ] ) . Drug-related AEs were reported by 27 ( 29.7 % ) patients in the SKI306X group and 22 ( 23.9 % ) patients in the celecoxib group . The most frequent drug-related AEs were epigastric pain ( 9/91 [ 9.9 % ] ) in the SKI306X group and glutamyltranferase elevation ( 4/92 [ 4.3 % ] ) in the celecoxib group . No significant between-group differences were observed in the prevalence of drug-related clinical - or laboratory-determined AEs . CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA Background Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity . The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis . Methods This was a 6-week , multicenter , r and omized , double-blind , double-dummy , parallel-group , phase III , non-inferiority clinical trial . The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale ( VAS ) . Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5 % confidence interval for treatment difference [ ( pain reduction in pelubiprofen group ) – ( pain reduction in celecoxib group ) ] was more than −10 mm . The secondary end points were as follows : non-inferiority of ( 1 ) reduction of Korean health assessment question naire ( KHAQ ) score ; ( 2 ) decreased duration of morning stiffness ; and ( 3 ) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment . Results Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication . Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity ( difference , mean ± SD 5.0 ± 20.1 ; 97.5 % CI , −2.3 to ∞ ) . Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points , such as , decrease in KHAQ score ( 0.0 ± 0.5 , 97.5 % CI −0.2 to ∞ ) , decrease in duration of morning stiffness ( median 0.0 minute in both groups ) , and decrease in the frequency ( 0.7 ± 3.5 , 97.5 % CI −0.6 to ∞ ) and total amount ( 0.7 ± 3.6 , 97.5 % CI −0.6 to ∞ ) of rescue medication uses during the 6 week study period . Safety analysis revealed 31.2 % patients in the pelubiprofen group and 20.6 % patients in the celecoxib  group experienced an adverse drug reaction ( ADR ) . The frequency of gastrointestinal ADRs was 20.8 % and 8.8 % , respectively . Conclusions Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients . However , more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group . ClinialTrials.gov identifier : NCT01781702 Objective : Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal ( GI ) risk who were enrolled in the CONDOR (  Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis ) trial . Methods : CONDOR was a 6-month , prospect i ve , double-blind , triple-dummy , parallel-group , r and omized , multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release ( SR ) 75 mg twice daily plus omeprazole 20 mg daily . Patients were Helicobacter pylori negative , had osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) , were aged ≥60 years , were with or without a history of gastroduodenal ulceration , or were ≥18 years with previous gastroduodenal ulceration . Patients ’ Global Assessment of Arthritis was determined at each study visit . Results : A total of 4484 patients were r and omized to treatment ( 2238 celecoxib , 2246 diclofenac SR ) and included in the intention-to-treat analyses . Least squares mean ( LSM ) ( st and ard error [ SE ] ) for Patients ’ Global Assessment of Arthritis was 3.219 ( 0.017 ) and 3.221 ( 0.017 ) at baseline for celecoxib and diclofenac SR ( p=0.90 ) . Improvement in both groups was similar in months 2 , 4 , and 6 ; at month 1 the LSM ( SE ) was 2.647 ( 0.017 ) and 2.586 ( 0.017 ) for celecoxib and diclofenac ( p=0.0025 ) . LSM difference ( SE ) from baseline to final visit demonstrated an improvement of 0.75 ( 0.02 ) in celecoxib-treated patients and 0.77 ( 0.02 ) in diclofenac SR-treated patients ( p=0.42 ) . Conclusions : Celecoxib and diclofenac plus omeprazole were shown to have similar efficacy in patients with OA and /or RA at increased GI risk who were enrolled in the CONDOR trial . Trial Registry : Trial was registered under Clinical Trials.gov identifier NCT00141102 CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a 
    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: Abstract Objective : To monitor the safety and efficacy profile of long-term treatment with diclofenac , nabumetone , meloxicam and celecoxib in patients with rheumatoid arthritis . Design and methods : This r and omised , prospect i ve clinical trial included a total of 461 subjects ( 313 females and 148 males ) with clinical ly diagnosed rheumatoid arthritis . Their average age was 46.9 ± 14.4 years ( range 20–69 years ) , and the average disease duration was 1333.7 ± 992.85 days . Subjects were r and omly assigned daily administration of one of the following : diclofenac 75–100 mg , meloxicam 15 mg , nabumetone l000 mg or celecoxib 200 mg . During the 6-month treatment period , a monthly patient interview was conducted to evaluate drug efficacy and safety . Results : 407 subjects successfully completed the 6-month treatment . Sixteen patients ( 12.2 % ) withdrew from the diclofenac group , 16 ( 12.2 % ) from the nabumetone group , 17 ( 11.8 % ) from the meloxicam group and five ( 9.1 % ) from the celecoxib group . Most withdrawals occurred during the first 3 months of treatment . Reasons for withdrawals in the first three groups were lack of efficacy ( 44.9 % ) and adverse effects ( 38.8 % ) . For the celecoxib group , high cost ( 80 % ) was the main reason for withdrawal . Adverse drug reactions to NSAIDs mostly occurred at an early stage of treatment , with an incidence rate of 31.9 % for the diclofenac group , 19.9 % for the nabumetone group , 25.2 % for the meloxicam group , and 7.27 % for the celecoxib group . Clinical efficacy rates for the four NSAIDs were positively related to the length of treatment . During the first 4 months , diclofenac , meloxicam and celecoxib showed better efficacy than nabumetone . There were no significant differences in efficacy during the fifth and sixth months . The overall 6-month effectiveness rates were 68.8 % for diclofenac , 59.8 % for nabumetone , 67.6 % for meloxicam and 69.1 % for celecoxib . Conclusions : Adverse drug reactions and their related withdrawals occurred mostly at an early stage of NSAID treatment , so it is crucial to strengthen pharmacovigilance during this period . Among the investigated NSAIDs , celecoxib did not prove to be superior to diclofenac , nabumetone or meloxicam with respect to its efficacy in the treatment of rheumatoid arthritis ; however , it did show good patient compliance and safety profiles BACKGROUND SKI306X , which consists of biologically active ingredients from Clematis m and sburica , Tricbosantbes kirilowii , and Prunella vulgaris , was developed and tested in pre clinical trials in Korea . Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect , and that it can delay the destruction of cartilage in rheumatoid arthritis ( RA ) . OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA . METHODS This study was a 6-week , multicenter , r and omized , double-blind , double-dummy , Phase III , noninferiority clinical trial . Eligible patients were aged 18 to 80 years , had a history of RA with a disease duration of > or =3 months , and were functional American College of Rheumatology ( ACR ) class I , II , or III before entry . After a washout period of 2 weeks , patients were r and omized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks . The primary end point was a change in patient assessment of pain intensity using a visual analog scale ( VAS ) . The secondary end points were a 20 % improvement in response rate as defined by the ACR ( ACR20 ) and the frequency of rescue medication use . Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups , and all patients were assessed for adverse events ( AEs ) , clinical laboratory data , and vital signs . AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator . RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and r and omized to 1 of 2 treatment groups . Ninety-one patients ( 10 male , 81 female ; mean [ SD ] age , 52.13 [ 12.64 ] years ; mean [ SD ] duration of RA , 9.08 [ 10.23 ] years ; no. [ % ] of ACR class I , II , and III , 13 [ 14.29 ] , 44 [ 48.35 ] and 34 [ 37.36 ] patients , respectively ) received SKI306X 200 mg TID and 92 patients ( 10 male , 82 female ; mean [ SD ] age , 51.78 [ 10.94 ] years ; mean [ SD ] duration of RA , 8.78 [ 7.78 ] years ; no. [ % ] of ACR class I , II , and III , 14 [ 15.22 ] , 44 [ 47.83 ] , and 34 [ 36.96 ] patients , respectively ) received celecoxib 200 mg BID . An analysis of the change in reported pain intensity as determined by VAS ( mm ) score between baseline and week 3 ( mean [ SD ] , 13.64 [ 16.62 ] vs 14.45 [ 15.89 ] ) , and between baseline and week 6 ( 18.4 [ 20.8 ] vs 17.9 [ 19.1 ] , respectively ) suggested that SKI306X was not inferior to celecoxib . The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 ( 16/87 [ 18.4 % ] vs 24/87 [ 27.6 % ] , respectively ) and at week 6 ( 29/87 [ 33.3 % ] vs 29/87 [ 33.3 % ] ) . The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 ( 54/87 [ 62.1 % ] vs 47/87 [ 54.0 % ] , respectively ) or week 6 ( 57/87 [ 65.5 % ] vs 49/87 [ 56.3 % ] ) . Drug-related AEs were reported by 27 ( 29.7 % ) patients in the SKI306X group and 22 ( 23.9 % ) patients in the celecoxib group . The most frequent drug-related AEs were epigastric pain ( 9/91 [ 9.9 % ] ) in the SKI306X group and glutamyltranferase elevation ( 4/92 [ 4.3 % ] ) in the celecoxib group . No significant between-group differences were observed in the prevalence of drug-related clinical - or laboratory-determined AEs . CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA Background Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity . The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis . Methods This was a 6-week , multicenter , r and omized , double-blind , double-dummy , parallel-group , phase III , non-inferiority clinical trial . The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale ( VAS ) . Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5 % confidence interval for treatment difference [ ( pain reduction in pelubiprofen group ) – ( pain reduction in celecoxib group ) ] was more than −10 mm . The secondary end points were as follows : non-inferiority of ( 1 ) reduction of Korean health assessment question naire ( KHAQ ) score ; ( 2 ) decreased duration of morning stiffness ; and ( 3 ) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment . Results Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication . Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity ( difference , mean ± SD 5.0 ± 20.1 ; 97.5 % CI , −2.3 to ∞ ) . Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points , such as , decrease in KHAQ score ( 0.0 ± 0.5 , 97.5 % CI −0.2 to ∞ ) , decrease in duration of morning stiffness ( median 0.0 minute in both groups ) , and decrease in the frequency ( 0.7 ± 3.5 , 97.5 % CI −0.6 to ∞ ) and total amount ( 0.7 ± 3.6 , 97.5 % CI −0.6 to ∞ ) of rescue medication uses during the 6 week study period . Safety analysis revealed 31.2 % patients in the pelubiprofen group and 20.6 % patients in the celecoxib  group experienced an adverse drug reaction ( ADR ) . The frequency of gastrointestinal ADRs was 20.8 % and 8.8 % , respectively . Conclusions Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients . However , more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group . ClinialTrials.gov identifier : NCT01781702 Objective : Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal ( GI ) risk who were enrolled in the CONDOR (  Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis ) trial . Methods : CONDOR was a 6-month , prospect i ve , double-blind , triple-dummy , parallel-group , r and omized , multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release ( SR ) 75 mg twice daily plus omeprazole 20 mg daily . Patients were Helicobacter pylori negative , had osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) , were aged ≥60 years , were with or without a history of gastroduodenal ulceration , or were ≥18 years with previous gastroduodenal ulceration . Patients ’ Global Assessment of Arthritis was determined at each study visit . Results : A total of 4484 patients were r and omized to treatment ( 2238 celecoxib , 2246 diclofenac SR ) and included in the intention-to-treat analyses . Least squares mean ( LSM ) ( st and ard error [ SE ] ) for Patients ’ Global Assessment of Arthritis was 3.219 ( 0.017 ) and 3.221 ( 0.017 ) at baseline for celecoxib and diclofenac SR ( p=0.90 ) . Improvement in both groups was similar in months 2 , 4 , and 6 ; at month 1 the LSM ( SE ) was 2.647 ( 0.017 ) and 2.586 ( 0.017 ) for celecoxib and diclofenac ( p=0.0025 ) . LSM difference ( SE ) from baseline to final visit demonstrated an improvement of 0.75 ( 0.02 ) in celecoxib-treated patients and 0.77 ( 0.02 ) in diclofenac SR-treated patients ( p=0.42 ) . Conclusions : Celecoxib and diclofenac plus omeprazole were shown to have similar efficacy in patients with OA and /or RA at increased GI risk who were enrolled in the CONDOR trial . Trial Registry : Trial was registered under Clinical Trials.gov identifier NCT00141102 CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a 
    Output:
    