Randomized Controlled Trial of Adalimumab in Patients With Nonpsoriatic Peripheral Spondyloarthritis Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial Real‐life 9‐year experience with adalimumab in psoriasis and psoriatic arthritis: results of a single‐centre, retrospective study Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis—results from a multicenter prospective randomized controlled trial and its post hoc analysis Obesity and the prediction of minimal disease activity: A prospective study in psoriatic arthritis Efficacy and safety of adalimumab in Chinese patients with moderate‐to‐severe plaque psoriasis: results from a phase 3, randomized, placebo‐controlled, double‐blind study Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study Body mass index and clinical response to infliximab in rheumatoid arthritis. Efficacy of adalimumab across subgroups of patients with moderate-to-severe chronic plaque psoriasis of the hands and/or feet: post hoc analysis of REACH A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis Body mass index influences the response to infliximab in ankylosing spondylitis Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Drug survival of biologic therapy in a large, disease‐based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) Infliximab, azathioprine, or combination therapy for Crohn's disease. Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. Influence of psoriatic arthritis on the efficacy of adalimumab and on the treatment response of other markers of psoriasis burden: subanalysis of the BELIEVE study. Body mass does not affect the remission of psoriatic arthritis patients on anti-TNF-α therapy Measures of Obesity and Risk of Crohn's Disease and Ulcerative Colitis Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial
To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis ( SpA ) Objective The aim of this study was to assess the efficacy and safety of adalimumab ( ADA ) , a recombinant human monoclonal antibody against tumour necrosis factor α ( TNF ) , for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis . Methods This 8-week , multicentre , r and omised , double-blind , placebo-controlled study ( NCT00385736 ) , conducted at 94 centres in North America and Europe , enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and /or immunosuppressants . Under the original study protocol , 186 patients were r and omised ( 1:1 ) to subcutaneous treatment with ADA160/80 ( 160 mg at week 0 , 80 mg at week 2 , 40 mg at weeks 4 and 6 ) or placebo . Subsequently , at the request of European regulatory authorities , the protocol was amended to include a second induction group ( ADA80/40 : 80 mg at week 0 , 40 mg at weeks 2 , 4 and 6 ) . The primary efficacy endpoint was clinical remission ( Mayo score ≤2 with no individual subscore > 1 ) at week 8 , assessed in 390 patients r and omised ( 1:1:1 ) to ADA160/80 , ADA80/40 , or placebo . Safety was assessed in all enrolled patients . Patients , study site personnel , investigators , and the sponsor were blinded to treatment assignment . Results At week 8 , 18.5 % of patients in the ADA160/80 group ( p=0.031 vs placebo ) and 10.0 % in the ADA80/40 group ( p=0.833 vs placebo ) were in remission , compared with 9.2 % in the placebo group . Serious adverse events occurred in 7.6 % , 3.8 % and 4.0 % of patients in the placebo , ADA80/40 , and ADA160/80 groups , respectively . There were two malignancies in the placebo group , none in the ADA groups . There were no cases of tuberculosis and no deaths . Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and /or immunosuppressants . Clinical trial NCT00385736 Background Observational studies in daily practice are an essential complement to pivotal r and omised controlled trials because their findings refer to larger and more diverse patient population s with common comorbidities , complex medical history , concomitant medications and longer follow‐up periods . Objectives To evaluate long‐term clinical outcomes of the anti‐TNF‐α monoclonal antibody , adalimumab , in patients with psoriasis ( PsO ) or psoriatic arthritis ( PsA ) referring to an Italian dermatological centre . Methods Single‐centre retrospective real‐world investigation with an observation period of up to 9 years . Results We review ed the records of 316 patients ( 117 with PsO and 199 with PsA ) treated with adalimumab and followed for up to 9 years . Safety and efficacy of adalimumab were consistent with those described in r and omised controlled trials ( RCTs ) and other observational studies . A rapid and sustained improvement of skin lesions ( evaluated as Psoriasis Area and Severity Index ( PASI ) 75 , PASI 90 and PASI 100 response rates ) was observed in the majority of patients , including those with body mass index ( BMI ) > 30 and with prior experience of biologic therapies ( including other anti‐TNFs ) . The safety profile  of adalimumab was confirmed also in elderly patients ( > 65 years ) . Conclusion Our real‐life experience shows that the long‐term treatment with adalimumab is effective and well tolerated in psoriatic patients , including overweight/obese , elderly and anti‐TNF‐experienced subjects Objective . To examine the clinical and ultrasonographic ( US ) outcomes of reducing methotrexate ( MTX ) dosage upon initiating adalimumab ( ADA ) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis ( RA ) . Methods . MUSICA ( NCT01185288 ) was a double-blind , r and omized , parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening . Patients were r and omized to high dosage  (  20 mg/week ) or low dosage ( 7.5 mg/week ) MTX ; all patients received 40 mg open-label ADA every other week for 24 weeks . The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein ( DAS28-CRP ) to test for noninferiority of low-dosage MTX using a 15 % margin . US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology , assessing synovial hypertrophy , vascularity , and bony erosions . Results . Rapid improvement in clinical indices was observed in both groups after addition of ADA . The difference in mean DAS28-CRP ( 0.37 , 95 % CI 0.07–0.66 ) comparing low-dosage ( 4.12 , 95 % CI 3.88–4.34 ) versus high-dosage MTX ( 3.75 , 95 % CI 3.52–3.97 ) was statistically significant and non-inferiority was not met . Statistically significant differences were not detected for most clinical , functional , and US outcomes . Pharmacokinetic and safety profiles were similar . Conclusion . In MUSICA , Week 24 mean DAS28-CRP , the primary endpoint , did not meet non-inferiority for the low-dosage MTX group . Although the differences between the 2 MTX dosage groups were small , our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA Background Infliximab ( IFX ) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis ( UC ) . A high serum trough level of  IFX ( TL ) is reported to be associated with sustained efficacy during maintenance treatment . As part of a phase 3 r and omized controlled trial of IFX in UC , we assessed the predictive value of the first TL at week 2 for short- and long-term response . Methods Patients received intravenous IFX 5 mg/kg or placebo at weeks 0 , 2 , and 6 . Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22 .  TL was measured by enzyme-linked immunosorbent assay . Post hoc analysis was then performed for TL and clinical outcomes . Results Clinical response rate at week 8 , the primary end point , was significantly higher in the IFX group than placebo ( p = 0.005 ) . The incidence of adverse events between groups was similar . Week 2 TL was significantly associated with a 14-week clinical activity index ( CAI ) remission . In multiple logistic regression analysis , the week 2 TL-to-CAI ratio ( TL/CAI , odds ratio 8.07 ; 95 % confidence interval 2.84–27.07 , p < 0.001 ) was an independent factor correlating with 14-week CAI remission . The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing . Conclusions IFX was confirmed to be effective and safe in this population . Our results suggest that the first TL at week 2 , in combination with clinical evaluation , is useful for predicting both short- and long-term outcomes , allowing an earlier decision between continuing IFX or switching to other options We prospect ively evaluated whether obesity impacts achievement of minimal disease activity ( MDA ) in subjects with psoriatic arthritis ( PsA ) Abstract Background This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF‐α inhibitor , adalimumab , for Chinese patients with moderate‐to‐severe plaque psoriasis . Methods In the 12‐week , double‐blind , placebo‐controlled Period A , patients were r and omized 4 : 1 to receive adalimumab 40 mg every‐other‐week ( following a single 80 mg dose ) , or placebo every‐other‐week . In the subsequent 12‐week , open‐label , Period B , all patients received adalimumab 40 mg every‐other‐week starting at week 13 , following a single , blinded dose at week 12 of adalimumab 80 mg or matching placebo ( for patients receiving placebo or adalimumab in Period A respectively ) . In Period A , efficacy was analysed for all r and omized patients and safety for all patients receiving ≥1 dose of the study drug . Results For the 425 patients in this study ( 87 placebo ; 338 adalimumab ) , a higher percentage r and omized to adalimumab achieved the primary endpoint of ≥75 % improvement from baseline in PASI score ( PASI 75 ) at week 12 : placebo 11.5 % ( 10/87 ) ; adalimumab 77.8 % ( 263/338 ; P < 0.001 ) . Physician 's Global Assessment of clear to minimal was achieved at week 12 by 14.9 % placebo ( 13/87 ) and 80.5 % adalimumab ( 272/338 ; P < 0.001 ) . For patients who received adalimumab at any time during the study ( All‐adalimumab Population ) , treatment‐emergent adverse events ( AEs ) were reported by 63.4 % ; the most common was upper respiratory infection ( 16.1 % ) . Serious AEs were reported by 3.5 % of the All‐adalimumab Population , and serious infectious AEs by 1.2 % , which include lung infection , pneumonia and tuberculosis [ 2 ( 0.5 % ) patients each ] . There was one death ( chronic heart failure ) . Conclusion In these Chinese patients with moderate‐to‐severe psoriasis , a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24 . Safety results were consistent with the known adalimumab safety profile ; no new safety signals were identified in the 24 weeks of treatment Introduction The aim of this study was to investigate patient reported outcomes ( PROs ) of functional ability and health related quality of life ( HRQoL ) in patients with early ( rheumatoid ) arthritis during one year of remission steered treatment . Methods In this study , 610 patients with early rheumatoid arthritis ( RA ) or undifferentiated arthritis ( UA ) were treated with methotrexate ( MTX ) and tapered high dose of prednisone .  Patients in early remission ( Disease Activity Score ( DAS ) < 1.6 after 4 months ) tapered prednisone to zero and when in persistent remission , also tapered MTX . Patients not in early remission were r and omized to either MTX + hydroxychloroquine + sulphasalazine + prednisone ( arm 1 ) or to MTX + adalimumab ( arm 2 ) . Every 4 months , patients filled out the Health Assessment Question naire ( HAQ ) and the McMaster Toronto Arthritis Patient Preference Question naire ( MACTAR ) , the Short Form 36 ( SF-36 ) and visual analogue scales ( VAS ) . Change scores were compared between treatment groups . The association with achieving remission was analyzed using linear mixed models . Results During year 1 , patients who achieved early remission had the most improvement in PROs with scores comparable to the general population . Patients in the r and omization arms showed less improvement . Scores were comparable between the arms . There was a significant association between achieving remission and scores of HAQ , MACTAR and physical HRQoL. Conclusions In early arthritis , PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission . In patients not in early remission , who were r and omized to two strategy arms , PROs improved less , with similar scores in both treatment arms . Trial registration sIS RCT N11916566 and EudraCT2006 - 006186 - OBJECTIVE Adipose tissue has immunomodulating effects in rheumatoid arthritis ( RA ) , although the exact role is , at present , unclear . The purpose of this study was to determine whether body mass index ( BMI ) affects response to  infliximab  in RA patients investigated prospect ively . METHODS In 89 patients with active RA , the BMI was calculated before initiation of infliximab treatment  ( 3 mg/kg intravenously ) . After 16 weeks of treatment , changes in disease activity were assessed with the Disease Activity Score in 28 joints ( DAS28 ) . RESULTS The mean ± SD BMI was 26 ± 5 kg/m(2 ) ( range 17 - 42 ) . The BMI correlated positively with the DAS28 at baseline ( r = 0.34 , P = 0.001 ) . Since selection of study patients according to DAS28 values could influence the clinical response to tumor necrosis factor ( TNF ) blockade due to regression to the mean because the clinical response is itself based on the change in the DAS28 values , analysis of covariance was used to correct for the baseline DAS28 . A highly significant , negative association between the BMI and the absolute decrease in the DAS28 after 16 weeks ( P = 0.001 ) was found also when adjusted for anti-citrullinated protein antibodies . CONCLUSION Although the infliximab dosage is based on body weight , RA patients with a high BMI responded less well to infliximab , a finding that held true when adjusted for the baseline DAS28 or anti-citrullinated protein antibody status . These results support the notion that adipose tissue may be involved in the pathophysiology of RA and could have implication s for other immune-mediated inflammatory conditions treated with TNF antagonists 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 Background  Etanercept plus methotrexate combination therapy  has not been adequately investigated in psoriasis Introduction The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences . The aim of this study was to determine whether body mass index ( BMI ) affects response to infliximab ( IFX ) in ankylosing spondylitis ( AS ) patients . Methods In 155 patients retrospectively included with active AS , the  BMI  was calculated before initiation of IFX treatment ( 5 mg/kg intravenously ) . After 6 months of treatment , changes from baseline in BASDAI , Visual Analogue Scale ( VAS ) pain , C-reactive protein ( CRP ) level , and total dose of nonsteroidal antiinflammatory drug ( NSAID  ) were dichotomized with a threshold corresponding to a decrease of 50 % of initial level of the measure , into binary variables assessing response to IFX ( BASDAI50 , VAS50 , CRP50 , NSAID50 ) . Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression . Results Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 ( P = 0.0003 ; OR , 0.87 ; 95 % CI ( 0.81 to 0.94 ) ) , VAS50 ( P < 0.0001 ; OR , 0.87 ; 95 % CI ( 0.80 to 0.93 ) ) ; CRP50 ( P = 0.0279 ; OR , 0.93 ; 95 % CI ( 0.88 to 0.99 ) ) , and NSAID50 ( P = 0.0077 ; OR , 0.91 ; 95 % CI ( 0.85 to 0.97 ) ) , criteria . According to the three WHO BMI categories , similar results were found for BASDAI50 ( 77.6 % , 48.9 % , and 26.5 % ; P < 0.0001 ) , VAS50 ( 72.6 % , 40.4 % , and 16.7 % ; P < 0.0001 ) ; CRP50 ( 87.5 % , 65.7 % , and 38.5 % ; P = 0.0001 ) , and NSAID50 ( 63.2 % , 51.5 % , and 34.6 % ; P = 0.06 ) . Conclusions This study provides the first evidence that a high BMI negatively influences the response to IFX in AS . Further prospect i ve studies , including assessment of the fat mass , pharmacokinetics , and adipokines dosages are m and atory to eluci date the role of obesity in AS IFX response BACKGROUND & AIMS The efficacy of infliximab for treating patients with ulcerative colitis has been established . METHODS The Active Ulcerative Colitis Trial (ACT)-1 and ACT-2 r and omized , double-blind , placebo-controlled studies evaluated infliximab induction and maintenance therapy in moderately to severely active ulcerative colitis . Overall , 728 patients received placebo or infliximab  ( 5 or 10 mg/kg ) intravenously at weeks 0 , 2 , and 6 , then every 8 weeks through week 46 ( ACT-1 ) or 22 ( ACT-2 ) . Colectomy , hospitalization , and surgery/procedure data through 54 weeks after the first infusion were obtained from ACT-1 , ACT-2 , and associated data sources . In the prespecified analysis , all data were combined to ascertain time to colectomy . Kaplan-Meier product-limit method was used to estimate the cumulative incidence of colectomy , and log-rank test was used to compare the combined infliximab group and placebo . RESULTS Eighty-seven percent ( 630 of 728 ) of patients had complete colectomy follow-up ; 13 % ( 98 of 728 ) of patients had a median follow-up of 6.2 months . The cumulative incidence of colectomy through 54 weeks was 10 % for infliximab and 17 % for placebo ( P = .02 ) , yielding an absolute risk reduction of 7 % . Compared with placebo , fewer ulcerative colitis-related hospitalizations and surgeries/ procedures per 100 patient-years of treatment occurred with infliximab therapy : 40 vs 20 ( P = .003 ) and 34 vs 21 ( P = .03 ) , respectively . Serious adverse events occurring in infliximab-treated patients included serious infections , tuberculosis , histoplasmosis , listeriosis , and malignancy . CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo Abstract Background Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis . Objective The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry ( PSOLAR ) . Methods PSOLAR is a large , prospect i ve , international , disease‐based registry of patients with psoriasis receiving ( or eligible for ) systemic therapy in a real‐world setting .  Drug survival is defined as the time from initiation to discontinuation ( stop/switch ) of biologic therapy on registry . The number of patients who discontinued each treatment and the duration of therapy were recorded . Using Kaplan – Meier survival curves and Cox‐regression analyses [ hazard ratios ( HR ) and 95 % confidence intervals ( CIs ) ] , time to discontinuation was compared across cohorts undergoing first‐ , second‐ or third‐line treatment with ustekinumab , infliximab , adalimumab or etanercept . Results As of the 2013 data cut , 12 095 patients with psoriasis were enrolled in PSOLAR . Of the 4000 patients initiating any new biologic therapy , approximately 3500 started a first‐line , second‐line or third‐line biologic therapy during the registry . Lack of effectiveness was the most common reason for discontinuation across biologic therapies . Based on the multivariate analysis , significantly shorter times to discontinuation were observed for infliximab [ HR ( 95%CI ) = 2.73 ( 1.48–5.04 ) , P = 0.0014 ] ; adalimumab [ 4.16 ( 2.80–6.20 ) , P < 0.0001 ] ; and etanercept [ 4.91 ( 3.28–7.35 ) P < 0.0001 ] compared with ustekinumab [ reference treatment ] ) for first‐line biologic use ; results were similar for treatment effects for second/third‐line therapies . Although limited in power , analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population . Conclusion Drug survival was superior for ustekinumab compared with infliximab , adalimumab and etanercept in patients with psoriasis BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . BACKGROUND & AIMS Certolizumab pegol ( CZP ) is a pegylated-conjugated Fab ' against tumor necrosis factor ( TNF ) . Additional data are needed regarding the efficacy of induction therapy with CZP in active Crohn 's disease ( CD ) . METHODS A placebo-controlled trial evaluated the efficacy of CZP therapy in 439 adults with moderate to severe CD naive to anti-TNF therapy . Patients were r and omized to receive CZP ( 400 mg subcutaneously ) or placebo at weeks 0 , 2 , and 4 . The primary end point was clinical remission at week 6 . RESULTS Clinical remission rates at week 6 in the CZP and placebo groups were 32 % and 25 % ( P = .174 ) , respectively . Remission rates at weeks 2 and 4 in the CZP and placebo groups were 23 % and 16 % ( P = .033 ) and 27 % and 19 % ( P = .063 ) , respectively . Clinical response rates at weeks 2 , 4 , and 6 in the CZP and placebo groups were 33 % and 20 % ( P = .001 ) , 35 % and 26 % ( P = .024 ) , and 41 % and 34 % ( P = .179 ) , respectively . There were significantly greater rates of clinical remission at week 6 for CZP in patients with increased concentrations of C-reactive protein ( ≥5 mg/L ) at entry . Serious adverse events developed in 5 % and 4 % of patients in the CZP and placebo groups , respectively . CONCLUSIONS The primary end point did not reach statistical significance . Significant differences between CZP and placebo were observed in patients who had increased concentrations of C-reactive protein when the study began . Future clinical trials should emphasize the treatment of patients who have objective evidence of inflammation in addition to symptoms of active disease BACKGROUND Biologic therapies are used to treat moderate to severe psoriasis , but evidence from r and omized , controlled studies is lacking regarding scalp-related effectiveness . OBJECTIVE To evaluate the efficacy and safety of etanercept for scalp symptoms ( erythema , in duration , scale , and percentage of scalp involvement ) in patients with moderate to severe plaque psoriasis and scalp involvement . METHODS In this r and omized , placebo-controlled study , adult patients with stable plaque psoriasis and significant scalp symptoms received etanercept 50 mg twice weekly ( BIW ) by subcutaneous injection ( SC ) for 12 weeks , followed by etanercept 50 mg once weekly ( QW ) and placebo QW ( Group A , n = 62 ) or SC placebo BIW for 12 weeks , followed by etanercept 50 mg BIW for 12 weeks ( Group B , n = 62 ) . The primary end point was percentage change in Psoriasis Scalp Severity Index ( PSSI ) at week 12 . RESULTS Demographics and disease characteristics were balanced : 56 % men , 73 % white , median age 41 years , median BMI 30.2 kg/m(2 ) . At week 12 , mean PSSI improvement was 86.8 % ( st and ard deviation [ SD ] , 18.0 % ) in Group A and 20.4 % ( SD , 39.3 % ) in Group B ( P < .0001 ) . At week 24 , mean PSSI improvements were as follows : Group A , 90.6 % ( SD 13.1 % ) ; Group B , 79.1 % ( SD 33.6 % ) . At week 12 , 51 of 59 ( 86 % ) Group A patients and 7 of 61 ( 11 % ) Group B patients achieved PSSI 75 ( P < .0001 ) . Three patients ( 2.7 % ) reported 5 serious adverse events : cholecystitis/cholelithiasis , fall/rib fracture , and metastatic malignant melanoma . LIMITATIONS The study was insufficiently powered to detect rare adverse events potentially associated with etanercept . CONCLUSIONS Etanercept is an effective , well-tolerated treatment for plaque psoriasis involving the scalp BACKGROUND Adalimumab is a fully human anti-TNF monoclonal antibody with demonstrated efficacy and safety in patients with moderate to severe psoriasis and psoriatic arthritis ( PsA ) . OBJECTIVE This study examined the effect of PsA on adalimumab treatment response in patients from the Phase IIIb BELIEVE trial ( NCT00574249 , Clinical Trials.gov registry ) , and response of other markers of disease burden to adalimumab  treatment . METHODS In this post hoc analysis , patients with or without a history of PsA and with moderate to severe psoriasis were r and omized to adalimumab plus adjunctive topical therapy ( calcipotriol/betamethasone dipropionate ) or monotherapy ( adalimumab plus matching topical vehicle ) . RESULTS Regardless of baseline PsA , improvement at Week 16 was seen in PASI 75 , pruritus , PSSI , and DLQI ( all patients ) , and mean NAPSI scores . Patients with PsA had HAQ improvement at Week 16 , and compared to patients without PsA , had higher VAS pain scores . This analysis represents the first publication of the influence of PsA and PsA plus body weight on patient response to adalimumab , and response of scalp psoriasis , nail psoriasis , and patient-reported outcomes to adalimumab . The incidence of AEs was similar among all patients ( 62 % ) , those with PsA ( 65 % ) and without PsA ( 60 % ) . The most common AEs were infections ( 27 % ) ; 4.2 % of all patients reported serious AEs . CONCLUSION Adalimumab treatment result ed in comprehensive , clinical ly relevant improvements from baseline PsA status , in skin , nails , quality of life , pain and pruritus . Despite having more severely affected disease and quality of life , patients with PsA did not respond to adalimumab significantly differently from patients without Objectives : There is evidence that fat tissue may influence the response to therapy in patients with arthritis . The aim of this study was to assess whether the body mass index ( BMI ) affects rates of clinical remission in patients with psoriatic arthritis ( PsA ) treated with anti-tumour necrosis factor (TNF)-α biological drugs . Method : We retrospectively studied 135 patients with active peripheral PsA ( 45 obese , 47 overweight , and 43 normal-weight ) . Baseline BMI was correlated with the clinical response to adalimumab , etanercept , or infliximab . After 36 months ( median , range 6–79 ) of treatment , disease remission rates were assessed using the Disease Activity Score in 28 joints ( DAS28 ) or the Simplified Disease Activity Index ( SDAI ) . Possible predictors of clinical outcomes were assessed by multivariate analysis . Results : At baseline , BMI was significantly correlated only with the Health Assessment Question naire ( HAQ ) score ( r = 0.21 , p = 0.02 ) and not with disease activity . BMI did not predict disease remission or changes in HAQ score  following anti-TNF-α therapy . Obese patients showed a significantly higher HAQ score and took significantly lower doses of prednisone than normal-weight or overweight patients , but their disease remission rates on the DAS28 ( 37 % ) or the SDAI ( 21 % ) were not significantly different from those of the other two groups ( 44 % and 21 % , respectively ) , regardless of the TNF-α inhibitor prescribed . Conclusions : In our retrospective analysis , disease activity and clinical response  to anti-TNF-α therapy in PsA do not seem to be affected by BMI . Further prospect i ve studies are needed to confirm these preliminary results Background : Obesity is associated with intestinal-specific inflammation . Nonetheless , a specific role of obesity in the etiology of inflammatory bowel disease is unclear . Methods : We conducted a prospect i ve cohort study of U.S. women enrolled in 1989 in the Nurses ' Health Study II . At baseline , we collected information on height , weight , waist and hip circumference , weight at age 18 , and body shape at age 20 . We used Cox proportional hazard models to calculate hazard ratios and 95 % confidence intervals ( CIs ) . Results : Among 111,498 women ( median age , 35 yr ) , we documented 153 cases of Crohn 's disease ( CD ) and 229 cases of ulcerative colitis ( UC ) more than 18 years of follow-up , encompassing 2,028,769 person-years . Compared with women with normal BMI , the multivariate-adjusted hazard ratios of CD were 2.33 ( 95 % CI , 1.15–4.69 ) for obese women at age 18 and 1.58 ( 95 % CI , 1.01–2.47 ) for obese women at baseline . Increasing weight gain between age 18 and baseline was associated with increased risk of CD ( Ptrend = 0.04 ) . Adolescent body habitus was also associated with risk of CD with a multivariate-adjusted hazard ratio of CD of 1.63 ( 95 % CI , 1.07–2.50 ) for women with overweight/obese body shape compared with women with a thin/slender body shape . We did not observe a significant association between any of these anthropometric measures and risk of UC . Conclusions : In a large prospect i ve cohort of U.S. women , measures of adiposity were associated with an increased risk of CD but not UC . Additional studies are needed to eluci date the biological mechanisms by which excess adiposity may increase the risk of CD Background and objectives Efficacy of adalimumab for ankylosing spondylitis ( AS ) has been established for Western population s but not in the Chinese population . This study is the first to evaluate the efficacy and safety of adalimumab in Chinese patients with AS . Methods Chinese adults with active AS who had an inadequate response or were intolerant to ≥1 non-steroidal anti-inflammatory drugs were r and omised to  adalimumab 40 mg ( N=229 )  or matching placebo ( N=115 ) subcutaneously every other week ( EOW ) for 12 weeks , followed by a 12-week open-label adalimumab 40 mg EOW phase . The primary efficacy endpoint was the percentage of patients meeting the Assessment in Spondyloarthritis International Society ( ASAS20 ) response criteria at week 12 . The recently developed AS Disease Activity Score ( ASDAS ) , as well as efficacy measures of spinal mobility , disease activity , physical function and quality of life were evaluated . Results At week 12 , adalimumab treatment result ed in a significantly greater percentage of ASAS20 responders than placebo ( 67.2 % versus 30.4 % , respectively ; p<0.001 ) . Differences in ASAS20 were observed as early as week 2 ( 42.8 % vs 6.1 % , respectively ; p<0.001 ) . The percentages of patients achieving ASAS40 , ASAS 5/6 and ASDAS inactive disease were significantly greater with adalimumab than placebo at week 12 ( all p<0.001 ) . Tuberculosis was reported in one patient . No cases of malignancy , lymphoma , demyelinating disease or lupus-like syndrome were reported during the study . Conclusions Adalimumab significantly reduced the signs and symptoms , improved physical function and quality of life of Chinese patients with active AS , and was generally safe and well tolerated in this population Drug survival reflects a drug 's effectiveness , safety , and tolerability . We assessed the drug survival of biologics used to treat psoriasis in a prospect i ve national pharmacovigilance cohort ( British Association of Dermatologists Biologic Interventions Register ( BADBIR ) ) . The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model . Data for patients on adalimumab ( n=1,879 ) , etanercept ( n=1,098 ) , infliximab ( n=96 ) , and ustekinumab ( n=450 ) were available . The overall survival rate in the first year was 77 % , falling to 53 % in the third year . Multivariate analysis showed that female gender ( hazard ratio ( HR ) 1.22 ; 95 % confidence interval ( CI ) : 1.09 - 1.37 ) , being a current smoker ( HR 1.19 ; 95 % CI : 1.03 - 1.38 ) , and a higher baseline dermatology life quality index ( HR 1.01 ; 95 % CI : 1.00 - 1.02 ) were predictors of discontinuation . Presence of psoriatic arthritis ( HR 0.82 ; 95 % CI : 0.71 - 0.96 ) was a predictor for drug survival . As compared with adalimumab , patients on etanercept ( HR 1.63 ; 95 % CI : 1.45 - 1.84 ) or infliximab ( HR 1.56 ; 95 % CI : 1.16 - 2.09 ) were more likely to discontinue therapy , whereas patients on ustekinumab were more likely to persist ( HR 0.48 ; 95 % CI : 0.37 - 0.62 ) . After accounting for relevant covariates , ustekinumab had the highest first-course drug survival . The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients Objectives Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) receiving MTX .  Methods Patients ( n=592 ) with active disease ( ≥6/66 swollen , ≥6/68 tender joints , C-reactive protein ≥1.0 mg/dl , rheumatoid factor positive and /or anticyclic citrullinated protein antibody positive at screening ) despite MTX ( 15–25 mg/week ) participated in this double-blind , placebo-controlled , phase 3 study . Patients were r and omised ( 2:1 ) to receive intravenous golimumab 2 mg/kg , or placebo infusions at weeks 0 and 4 and every ( q ) 8 weeks ; patients continued MTX . Placebo patients with < 10 % improvement in combined swollen/tender joint counts at week 16 could early escape to intravenous golimumab 2 mg/kg . The primary endpoint was week 14 American College of Rheumatology 20 % ( ACR20 ) response . Analyses employed non-responder imputation and last-observation-carried-forward . Results At week 14 , significantly ( p<0.001 ) larger proportions of golimumab+MTX than placebo+MTX patients achieved ACR20 response ( 59 % vs 25 % , respectively ) , a disease activity score of good/moderate ( EULAR ) response ( 81 % vs 40 % ) , and greater median improvement in health assessment question naire scores ( 0.500 vs 0.125 ) . Improvements versus placebo+MTX were observed by week 2 . Similar proportions of patients receiving golimumab+MTX and placebo+MTX , respectively , reported adverse events through week 16 ( 47 % and 44 % ) and week 24 ( 53 % and 49 % ) . Serious adverse events were reported by more golimumab+MTX ( 4.1 % ) than placebo+MTX ( 2 % ) patients at week 24 . Conclusion The addition of intravenous golimumab rapidly and significantly improved signs and symptoms in patients with active RA despite ongoing MTX , in some patients by week 2
OBJECTIVES We sought to evaluate the association between obesity and response to anti-tumor necrosis factor-α ( TNF ) agents , through a systematic review and meta- analysis .