***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: Objective : The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis ( RA ) despite methotrexate therapy . Methods : Patients were r and omly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules ( group 1 , n = 133 ) , golimumab 100 mg injections plus placebo capsules ( group 2 , n = 133 ) , golimumab 50 mg injections plus methotrexate capsules ( group 3 , n = 89 ) , or golimumab 100 mg injections plus methotrexate capsules ( group 4 , n = 89 ) . Injections were administered subcutaneously every 4 weeks . The co- primary endpoints were the proportion of patients with 20 % or greater improvement in the American College of Rheumatology criteria ( ACR20 ) at week 14 and the change from baseline in the health assessment question naire-disability index ( HAQ-DI ) score at week 24 . Results : The proportion of patients who achieved an ACR20 response at week 14 was 33.1 % in the placebo plus methotrexate group , 44.4 % ( p = 0.059 ) in the golimumab 100 mg plus placebo group , 55.1 % ( p = 0.001 ) in the golimumab 50 mg plus methotrexate group and 56.2 % ( p<0.001 ) in the golimumab 100 mg plus methotrexate group . At week 24 , median improvements from baseline in HAQ-DI scores were 0.13 , 0.13 ( p = 0.240 ) , 0.38 ( p<0.001 ) and 0.50 ( p<0.001 ) , respectively . During the placebo-controlled portion of the study ( to week 16 ) , serious adverse events occurred in 2.3 % , 3.8 % , 5.6 % and 9.0 % of patients and serious infections occurred in 0.8 % , 0.8 % , 2.2 % and 5.6 % , respectively . Conclusion : The addition of golimumab to methotrexate  in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function Objective Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis ( RA ) . The safety and efficacy of ustekinumab , a human monoclonal anti-IL-12/23 p40 antibody , and guselkumab , a human monoclonal anti-IL-23 antibody , were evaluated in adults with active RA despite methotrexate ( MTX ) therapy . Methods Patients were r and omly assigned ( 1:1:1:1:1 ) to receive placebo at weeks 0 , 4 and every 8 weeks ( n=55 ) , ustekinumab 90 mg at weeks 0 , 4 and every 8 weeks ( n=55 ) , ustekinumab 90 mg at weeks 0 , 4 and every 12 weeks ( n=55 ) , guselkumab 50 mg at weeks 0 , 4 and every 8 weeks ( n=55 ) , or guselkumab 200 mg at weeks 0 , 4 and every 8 weeks ( n=54 ) through week 28 ; all patients continued a stable dose of MTX ( 10–25 mg/week ) . The primary end point was the proportion of patients with at least a 20 % improvement in the American College of Rheumatology criteria ( ACR 20 ) at week 28 . Safety was monitored through week 48 . Results At week 28 , there were no statistically significant differences in the proportions of patients achieving an ACR 20 response between the combined ustekinumab group ( 53.6 % ) or the combined guselkumab group ( 41.3 % ) compared with placebo ( 40.0 % ) ( p=0.101 and p=0.877 , respectively ) . Through week 48 , the proportions of patients with at least one adverse event ( AE ) were comparable among the treatment groups . Infections were the most common type of AE . Conclusions Treatment with ustekinumab or guselkumab did not significantly reduce the signs and symptoms of RA . No new safety findings were observed with either treatment . Trial registration number NCT01645280 To evaluate ixekizumab , an anti – interleukin‐17A ( anti – IL‐17A ) monoclonal antibody , in 2 population s of rheumatoid arthritis ( RA ) patients : biologics‐naive patients and patients with an inadequate response to tumor necrosis factor ( TNF ) inhibitors Objectives Mavrilimumab , a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor , was evaluated in a phase 2 r and omised , double-blind , placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis ( RA ) . Methods Subcutaneous mavrilimumab ( 10 mg , 30 mg , 50 mg , or 100 mg ) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy . The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score ( DAS28-CRP ) at week 12 . Results 55.7  % of mavrilimumab-treated subjects met the primary endpoint versus 34.7 % placebo ( p=0.003 ) at week 12 ; for the 10 mg , 30 mg , 50 mg , and 100 mg groups , responses were 41.0 % ( p=0.543 ) , 61.0 % ( p=0.011 ) , 53.8 % ( p=0.071 ) , and 66.7 % ( p=0.001 ) respectively . Response rate differences  from placebo were observed at week 2 and increased throughout the treatment period . The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 ( 23.1 % vs 6.7 % , p=0.016 ) , all categories of the American College of Rheumatology ( ACR ) criteria ( ACR20 : 69.2 % vs 40.0 % , p=0.005 ; ACR50 : 30.8 % vs 12.0 % , p=0.021 ; ACR70 : 17.9 % vs 4.0 % , p=0.030 ) , and the Health Assessment Question naire Disability Index ( −0.48 vs −0.25 , p=0.005 ) . A biomarker-based disease activity score showed a dose-dependent decrease at week 12 , indicating suppression of disease-related biological pathways . Adverse events were generally mild or moderate in intensity . No significant hypersensitivity reactions , serious or opportunistic infections , or changes in pulmonary parameters were observed . Conclusions Mavrilimumab induced rapid clinical ly significant responses in RA subjects , suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA Background Placebo effect is one of the method ological difficulties in dry eye clinical trials . If we could eluci date the tendencies of the placebo response and find predictors , we could reduce the placebo response in clinical trials for dry eye . In this study , we investigated the predictive factors for the placebo effect in dry eye clinical trials . Methods A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled  r and omised clinical trials were analysed by simple and multivariable regression analysis . The  corneal fluorescein ( FL ) staining score and dry eye symptoms were studied at week 4 . The variables of interest included gender , age , complications of Sjögren ’s syndrome , Schirmer ’s test I value , tear break-up time and conjunctival hyperaemia score . We also conducted a stratified analysis according to the patients ’ age . Results Among all the studied endpoints , the baseline scores were significantly related to the corresponding placebo response . In addition , for the FL score and the dryness score , age was a significant predictor of the placebo response ( p=0.04 and p<0.0001 , respectively ) . Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores . Conclusion The baseline scores and age were predictive factors of the placebo response in frequently used endpoints , such as FL score or dryness symptoms . These patient characteristics can be controlled by study design , and our findings enable the design of more efficient placebo-controlled studies with good statistical power BACKGROUND Rheumatoid arthritis is a heterogeneous chronic disease , and no therapeutic agent has been identified which is universally and persistently effective in all patients . We investigated the effectiveness of tofacitinib ( CP-690,550 ) , a novel oral Janus kinase inhibitor , as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis . METHODS We did a 6-month , double-blind , parallel-group phase 3 study at 82 centres in 13 countries , including North America , Europe , and Latin America . 399 patients aged 18 years or older with moderate-to-severe rheumatoid arthritis and inadequate response to tumour necrosis factor inhibitors ( TNFi ) were r and omly assigned in a 2:2:1:1 ratio with an automated internet or telephone system to receive twice a day treatment with : tofacitinib 5 mg ( n=133 ) ; tofacitinib 10 mg ( n=134 ) ; or placebo ( n=132 ) , all with methotrexate . At month 3 , patients given placebo advanced to either tofacitinib 5 mg twice a day ( n=66 ) or 10 mg twice a day ( n=66 ) . Primary endpoints included American College of Rheumatology (ACR)20 response rate , mean change from baseline in Health Assessment Question naire-Disability Index ( HAQ-DI ) , and rates of disease activity score (DAS)28 - 4(ESR ) less than 2·6 ( referred to as DAS28<2·6 ) , all at month 3 . The full analysis set for the primary analysis included all r and omised patients who received at least one dose of study medication and had at least one post-baseline assessment . This trial is registered with www . Clinical Trials.gov , number NCT00960440 . FINDINGS At month 3 , ACR20 response rates were 41·7 % ( 55 of 132 [ 95 % CI vs placebo 6·06 - 28·41 ] ; p=0·0024 ) for tofacitinib 5 mg twice a day and 48·1 % ( 64 of 133 ; [ 12·45 - 34·92 ] ; p<0·0001 ) for tofacitinib 10 mg twice a day versus 24·4 % ( 32 of 131 ) for  placebo . Improvements from baseline in HAQ-DI were -0·43 ( [ -0·36 to -0·15 ] ; p<0·0001 ) for 5 mg twice a day and -0·46 ( [ -0·38 to -0·17 ] ; p<0·0001 ) for 10 mg twice a day tofacitinib versus -0·18 for placebo ; DAS28<2·6 rates were 6·7 % ( eight of 119 ; [ 0 - 10·10 ] ; p=0·0496 ) for 5 mg twice a day tofacitinib and 8·8 % ( 11 of 125 [ 1·66 - 12·60 ] ; p=0·0105 ) for 10 mg twice a day tofacitinib versus 1·7 % ( two of 120 ) for  placebo . Safety was consistent with phase 2 and 3 studies . The most common adverse events in months 0 - 3 were diarrhoea ( 13 of 267 ; 4·9 % ) , nasopharyngitis ( 11 of 267 ; 4·1 % ) , headache ( 11 of 267 ; 4·1 % ) , and urinary tract infection ( eight of 267 ; 3·0 % ) across tofacitinib groups , and nausea ( nine of 132 ; 6·8 % ) in the placebo group . INTERPRETATION In this treatment-refractory population  , tofacitinib with methotrexate had rapid and clinical ly meaningful improvements in signs and symptoms of rheumatoid arthritis and physical function over 6 months with manageable safety . Tofacitinib could provide an effective treatment option in patients with an inadequate response to TNFi . FUNDING Pfizer Abstract Objective . A phase IIa study investigated efficacy and safety/tolerability of ascending doses of mavrilimumab ( anti-granulocyte-macrophage colony-stimulating factor receptor [GM-CSFR] 
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No background DMARD treatment was also a negative predictor ( albeit statistically non-significant ) .
Our meta- analysis suggests that study location , patient population , and a background DMARD treatment influence placebo ACR20 .