National Center for Biotechnology Information
Evidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Asahina et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bc2FoaW5hPC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48
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ADDIN EN.CITE.DATA 106Year: 2010Study name: The Adalimumab M04-688 Study GroupCountry: JapanQuality rating: FairFUNDING:Sponsored by Abbott Japan, Tokyo, Japan, and Eisai, Tokyo, Japan; Abbot Laboratories provided medical writing support.RESEARCH OBJECTIVE:To evaluate the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis.DESIGN & SIZE: Study design: Phase II/III RCTSetting: multicenter (42 sites in Japan)Number screened: Not ReportedNumber eligible: 235 consentedNumber enrolled: 169Run-in/Wash-out period: 14 days for topical therapies and phototherapy, 28 days for systemic therapy and PUVA.INTERVENTION: Dose: Duration: Sample size:Drug 1Adalimumab 40mg every other week24 weeks38Drug 2Adalimumab 40mg every other wk starting wk 2, after loading dose of 80mg at wk 024 weeks43Drug 3Adalimumab 80mg every other week24 weeks42Drug 4Placebo every other week24 weeks46INCLUSION CRITERIA:≥20 years of age, a clinical diagnosis of moderate to severe chronic plaque psoriasis, defined by a score of 12 or greater on the Psoriasis Area and Severity Index (PASI) and body surface area (BSA) involvement of 10% or greater, for at least 6 months, during which time plaque psoriasis was stable for at least the recent two monthsEXCLUSION CRITERIA: previous exposure to anti-TNF therapy, other active skin diseases or skin infections, diagnosis of systemic lupus erythematosus, scleroderma, or rheumatoid arthritis, history of central nervous system demyelinating disease, cancer, lymphoma, leukemia, tuberculosis, or lymphoproliferative disease, positive serology for anti-HIV antibody, hepatitis B surface antigen, anti-hepatitis C antibody, active infectious disease, immunosuppressive disease, or abnormal hematological, hepatic, or renal valuesOTHER MEDICATIONS/ INTERVENTIONS ALLOWED:weak or medium-potency topical corticosteroids to palms, soles, face, scalp, and groinAuthors: Asahina et al.Year: 2010POPULATION CHARACTERISTICS: Adalimumab 40mgAdalimumab 40mgwith 80mg loading doseAdalimumab 80mgPlaceboMean age (years):47.8±12.8144.2±14.3243.5±12.4043.9±10.75Sex (% female):6 (15.8%)8 (18.6%)7 (16.7%)5 (10.9%)Ethnicity: JapaneseJapaneseJapaneseJapaneseClass na?ve:100%100%100%100%Other germane population qualities:Mean PASIMean body surface area involvement25.44±8.97743.3%30.24±10.94648.3%28.27±11.02946.1%29.10±11.76746.7%Mean duration of psoriasis14.2 yrs ±9.29 yrs14.0 yrs ±7.36 yrs11.6 yrs ±7.45 yrs15.5 yrs ±8.83 yrsReceived prior systemic therapy of nonbiologics within 6 mo prior to screening (%)47.4%41.9%42.9%37.0%Phototherapy received within 6 months prior to screening (%)18.4%23.3%16.7%41.3%RESULTS: Primary Outcome Measures: %of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16: Drug 1: 57.9%; Drug 2: 62.8%; Drug 3: 81.0%; Placebo 4.3% (p<0.001).Secondary Outcome Measures: % of patients achieving PASI 50, PASI 90 and Physicians Global Assessment of “clear” or “minimal”, changes in health-related QOL were assessed by the Dermatology Life Quality Index (DLQI) and Short Form 36 (SF-36) Health Survey at week 16; PASI 50: Drug 1: 73.7%; Drug 2: 81.4%; Drug 3: 90.5%; Placebo 19.6%; PASI 90: Drug 1: 36.8%; Drug 2: 39.5%; Drug 3: 61.9%; Placebo: 0%; PGA “Clear” or “Minimal”: Drug 1: 44.7%; Drug 2: 60.5%; Drug 3: 78.6%; Placebo: 4: 8.7%; DLQI change from baseline to week 16: Drug 1: -3.9; Drug 2: -5.1; Drug 3: -6.8; Placebo:+1.0 (p<0.001 for PASI, PGA, and DLQI); SF-36change from baseline to week 16: Drug 1: 3.7 (p<0.05); Drug 2: 4.6 (p<0.01); Drug 3: 4.9 (p<0.001); Placebo: -0.4(p>0.05).Authors: Asahina et al.Year: 2010METHOD OF ADVERSE EVENTS REPORTING:Adverse events were assessed at each, every other week, visit. Laboratory evaluations and vital signs were conducted at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24.ADVERSE EVENTS (%): Drug 1Drug 2Drug 3Drug 4Overall adverse effects reported:37 (97.4%)39 (90.7%)38 (90.5%)41 (89.1)Infections55.3%41.9%50.0%50.0%URTIabnormal LFTsee belowsee belowsee belowsee belowherpes simplexpneumoniatb0%0%0%not stated: assume 0%ISR15.8%18.6%14.3%6.5%ALT 15.8%16.3%4.8%6.5%AST 7.9%9.3%2.4%4.3%GGT Hepatic eventHepatobiliary disorders13.2%39.5%7.9%2.3%30.2%7.0%2.4%23.8%11.9%0%8.7%0%ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 22 (13.0%)Attrition differential high: Possibly, for comparisons of Drug 1 and 3 vs Drug 2Drug 14 (10.5%)2 (5.3%)Drug 28 (18.6%)5 (11.6%)Drug 34 (9.5%)3 (7.1%)Drug 46 (13.0%)5 (10.9%)URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Brimhall et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmltaGFsbDwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+
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ADDIN EN.CITE.DATA 107Year: 2008Country: FUNDING:NoneDESIGN: Study design: Systematic reviewNumber of patients: 7,931AIMS OF REVIEW:To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasisSTUDIES INCLUDED IN META-ANALYSISALE (three trials) n=1289EFA (five trials) n=3130ETA (four trials) n=2017INF (four trials) n=1495TIME PERIOD COVERED:MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and . were searched from inception to June 2005; an updating search was conducted in July 2006 to capture reports from the interim periodCHARACTERISTICS OF INCLUDED STUDIES:Randomized, controlled, double-blind, monotherapy trialsCHARACTERISTICS OF INCLUDED POPULATIONS:Patients with psoriasisAuthors: Brimhall et al.Year: 2008CHARACTERISTICS OF INTERVENTIONS:ALE vs. placeboEFA vs. placeboETA vs. placeboINF vs. placeboMAIN RESULTS:NNT (95% CI)PASI 50PASI 75PASI 90ALE4(3.07–4.48)8 (5.05–12.20)N/AEFA3(3.26–4.48)4(3.36–5.24)N/AETAN/A3(2.07–2.49)5(4.29–5.88)INFN/A2(1.24–1.38)2(1.67–2.31)ADVERSE EVENTS:NNH (95%CI)ALE15(7.63–142.86)EFA9(7.30–13.88)ETA46(–48–14)INF9(5.99–19.61)COMPREHENSIVE LITERATURE SEARCH STRATEGY:YesSTANDARD METHOD OF APPRAISAL OF STUDIES:YesQUALITY RATING: FairEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Gordon et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb3Jkb248L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 109Year: 2006Country: US and CanadaFUNDING:Abbott LabsRESEARCH OBJECTIVE:Efficacy and safety of ADA in patients with moderate to severe plaque psoriasis. After 12 week all patients were switched to active arms.DESIGN: Study design: RCTSetting: MulticenterSample size: 147INTERVENTION: Dose: Duration: Sample size:PlaceboN/A12 weeks52ADA EOW80 mg at week 0 and 40 mg EOW12 weeks45ADA Weekly80 mg at week 0 and 40 mg weekly12 weeks50INCLUSION CRITERIA:Men and women age 18 years and older with plaque psoriasis of at least 1-year duration and involving 5% or more of their body surface area.EXCLUSION CRITERIA:History of neurologic symptoms suggestive of central nervous system demyelinating disease, or with a history of cancer or lymphoproliferative disease (other than successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix)OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Low to mid dose topical corticosteroidsAuthors: Gordon et al. and Shikiar et al.Year: 2006POPULATION CHARACTERISTICS: Mean age (years):Sex (% female):Ethnicity (% Caucasian): Other germane population qualities: Mean PASIMean body surface area involvementMean duration of psoriasis -yrsReceived prior systemic therapy (%)Groups similar at baseline: Placebo43359216.02819NRADA EOW46298916.72921NRADA Weekly44349014.52518NROUTCOME ASSESSMENT: Primary Outcome Measures: PASI 75% and DLQI at 12 weeksSecondary Outcome Measures: PASI 75 at 24 weeks and PGA, SF-36 Health Survey, and Euro QoL-5D (EQ-5D)Timing of assessments: weeks 0, 1, 2, and 4, and then every 4 or 8 weeks thereafter.RESULTS:Health Outcome Measures:PASI 75% at 12 weeks Placebo 4% ADA EOW 53% ADA WK 80%PASI 100% at 12 weeks Placebo 0% ADA EOW 11% ADA WK 26%DLQI change at 12 weeks Placebo 1.3% (3.3, 0.7) ADA EOW 10.8 (13.1, 8.5) ADA WK 11.5 (13.6, 9.4) ADA(both) vs. placebo P < 0.001EQ-5D Index score change at 12 weeks Placebo 0.01 (0.07, 0.1) ADA EOW 0.21 (0.11, 0.31) ADA WK 0.19 (0.09, 0.28) ADA(both) vs. placebo P < 0.001EQ-5D VAS change at 12 weeks Placebo 0.5 (5.7, 6.8) ADA EOW 17.9 (10.5, 25.2) ADA WK 10.7 (4.1, 17.4) ADA EOW vs. placebo P < 0.001 and ADA WK vs. placebo P = 0.013SF-36 PCS change at 12 weeks Placebo 0.5 (2.4, 3.5) ADA EOW 3.6 (0.2, 7.0) ADA WK 5.5 (2.4, 8.6) ADA EOW vs. placebo P = 0.118 and ADA WK vs. placebo P = 0.010SF-36 MCS change at 12 weeks Placebo 0.1 (3.5, 3.3) ADA EOW 7.8 (3.9, 11.8) ADA WK 5.2 (1.6, 8.9) ADA EOW vs. placebo P < 0.001 and ADA WK vs. placebo P = 0.017Authors: Gordon et al. and Shikiar et al.Year: 2006ADVERSE EVENTS: Overall adverse effects reported:infectionsDyspepsiaNauseaInjection site painPlacebo67.3%005.8%5.8%ADA EOW62.2%006.7%6.7%ADA Weekly78.0%2.0%8.0%2.0%12.0%Significant differences in adverse events:None reportedANALYSIS: ITT: YesPost randomization exclusions: 1ADEQUATE RANDOMIZATION:NRADEQUATE ALLOCATION CONCEALMENT:NRBLINDING OF OUTCOME ASSESSORS:NRATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 7 (5%)Attrition differential high: NoPlacebo3.8%1.9%ADA EOW4.4%4.4%ADA Weekly6.0%6.0%QUALITY RATING: Fair Evidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Griffiths et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmlmZml0aHM8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy
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ADDIN EN.CITE.DATA 110Year: 2010Study name: - Country: WorldwideQuality rating: FAIRFUNDING:Centocor Research and Development (pharmaceutical industry)RESEARCH OBJECTIVE:To compare two biologic agents, ustekinumab and etanercept, for the treatment of psoriasisDESIGN & SIZE: Study design: head-to-head RCTSetting: multi-centerNumber screened: 1,175Number eligible: not reportedNumber enrolled: 903Run-in/Wash-out period: noINTERVENTION: Dose: Duration: Sample size:ETA50 mg twice weekly12 weeks347UST45 mg at weeks 0 and 412 weeks209UST90 mg at weeks 0 and 412 weeks347INCLUSION CRITERIA:≥18 years of age, diagnosis of plaque psoriasis at least 6 months earlier, candidates for phototherapy or systemic treatment, score ≥12 on PASI, score ≥3 on physician’s global assessment; involvement of ≥10% of body-surface area; inadequate response, intolerance or contraindication to ≥1 conventional systemic agent (i.e., methotrexate, cyclosporine, or psoralen plus UVA), and no previous treatment with UST or ETA.EXCLUSION CRITERIA:Nonplaque or drug-induced forms of psoriasis, recent serious infection, history of chronic or recurrent infectious disease, known malignant condition (other than treated basal- or squamous-cell skin cancer or cervical cancer in situ with no evidence of recurrence for ≥5 years), receipt of conventional systemic therapy or phototherapy within 4 weeks before enrollment, topical psoriasis agents within 2 weeks, investigational drugs within 4 weeks or 5 half-lives, biologic agents within 3 months or 5 half-lives.OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:None reportedAuthors: Griffiths et al.Year: 2010POPULATION CHARACTERISTICS: ETAUST 45 mgUST 90 mgMean age (years):45.745.144.8Sex (% female):29.1%36.4%32.6%Ethnicity: 91.1% white92.3% white89.0% whiteClass na?ve:88.2%87.6%89.6%Other germane population qualities:Mean PASI18.620.519.9Mean body surface area involvement23.8%26.7%26.1%Mean duration of psoriasis18.8 years18.9 years18.7 yearsReceived prior systemic therapy (%)57.3%61.7%52.4%RESULTS: Primary Outcome Measures: 56.8% of ETA group had ≥75% improvement in PASI score compared with 67.5% of UST 45 mg group (P=0.01 vs. ETA)and 73.8% of UST 90 mg group (P<0.001 vs. ETA).Secondary Outcome Measures: 23.1% of ETA group had ≥90% improvement in PASI score compared with 36.4% of UST 45 mg group (P<0.001 vs. ETA) and 44.7% of UST 90 mg group (P<0.001 vs. ETA).49.0% of ETA group had cleared or minimal disease (physician’s global assessment score=0 or 1) compared with 65.1% of UST 45 mg group (P<0.001 vs. ETA) and 70.6% of UST 90 mg group (P<0.001 vs. ETA).8.6% of ETA group had cleared disease (physician’s global assessment score=0) compared with 16.3% of UST 45 mg group (P=0.006 vs. ETA) and 26.2% of UST 90 mg group (P<0.001 vs. ETA).Authors: Griffiths et al.Year: 2010METHOD OF ADVERSE EVENTS REPORTING:Safety was evaluated by assessing adverse events and routine hematologic and laboratory values. Possible major cardiovascular events were adjudicated by an independent panel of academic cardiologists. Serum samples were evaluated for antibodies to UST.ADVERSE EVENTS (%): ETAUST 45 mgUST 90 mgOverall adverse effects reported:70.0%66.0%69.2%Infections29.1%30.6%29.7%URTI5.8%6.2%6.3%abnormal LFTNRNRNRherpes simplexNRNRNRpneumoniaNRNRNRtbNRNRNRISR24.8%4.3%3.7%nonmelanoma skin cancer0.0%1.0%0.3%back pain2.0%6.7%4.3%≥ serious adverse event1.2%1.9%1.2%ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 2.7%Attrition differential high: NoETA3.2%2.3%UST 45 mg3.8%1.9%UST 90 mg1.4%1.2%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Krueger et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LcnVlZ2VyPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48
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ADDIN EN.CITE.DATA 111Year: 2007Study name: CNTO 1275 Psoriasis Study GroupCountry: MultinationalQuality rating: FairFUNDING:CentocorRESEARCH OBJECTIVE:To evaluate the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasisDESIGN & SIZE: Study design: RCT – phase 2Setting: Multi-centerNumber screened: 487Number eligible: NRNumber enrolled: 320Run-in/Wash-out period: NoneINTERVENTION: PlaceboInterleukin-12/23 Monoclonal AntibodyDose: Duration: Sample size:NA36 weeks6445 mg36 weeks6490 mg36 weeks644 x 45 mg36 weeks644 x 90 mg36 weeks64INCLUSION CRITERIA:Men and women (age, ≥18 years); a diagnosis of plaque psoriasis for at least 6 months, candidates for phototherapy or systemic therapy, a baseline score on the psoriasis area-and-severity index of 12 or higher (on a scale of 0 to 72, with higher scores indicating more severe disease), and involvement of at least 10% body-surface areaEXCLUSION CRITERIA:Nonplaque forms of psoriasis; recent serious systemic or local infection; active or latent tuberculosis, asthma, or a known malignancy within the previous 5 years (except treated basal-cell skin cancer); previous treatment with any agent specifically targeting interleukin-12 or interleukin-23; biologic or investigational agents within the previous month or five drug half-lives; conventional systemic psoriasis therapy or phototherapy within the previous 4 weeks; or topical psoriasis treatment within the previous 2 weeks.OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:See aboveAuthors: Krueger et al. Year: 2007PlaceboInterleukin-12/23 Monoclonal AntibodyPOPULATION CHARACTERISTICS: NA45 mg90 mg4 x 45 mg4 x 90 mgMean age (years):4446464544Sex (% female):2841273919Ethnicity: NRNRNRNRNRClass na?ve:NRNRNRNRNROther germane population qualities:Mean PASI19.919.018.818.919.0Mean body surface area involvement26.628.526.327.427.4Mean duration of psoriasis16.919.117.919.817.3Received prior systemic therapy (%)6161587255RESULTS: 12 week changePlaceboInterleukin-12/23 Monoclonal AntibodyNA45 mg90 mg4 x 45 mg4 x 90 mgMean PASI (SD)16.4 (8.1)6.5 (6.6)*5.7 (7.0)*3.6 (4.2)*3.0 (3.7)*50% improved n (%)7 (11)48 (75)*52 (81)*59 (92)*59 (92)*75% improved n (%)1 (2)33 (52)*38 (59)*43 (67)*52 (81)*90% improved n (%)1 (2)15 (23)19(30)28 (44)*33 (52)*Physician – clear or excellent032 (50)*34 (53)*46 (72)*53 (83)*Clear04 (6)**11 (17)*10 (16)*15 (23)*Change in DLQI-2.2 (4.2)-7.4 (6.2)*-9.8 (7.0)*-10.2 (6.8)*-8.4 (6.2)*DLQI score1 (2)13 (20)*19 (30)*27 (42)*26 (41)** P < 0.001** P not calculatedAuthors: Krueger et al.Year: 2007METHOD OF ADVERSE EVENTS REPORTING: NRADVERSE EVENTS (%): at 20 weeksPlaceboInterleukin-12/23 Monoclonal AntibodyOverall adverse effects reported:72%79%434Infections39Serious AEs1PlaceboInterleukin-12/23 Monoclonal AntibodyNA45 mg90 mg4 x 45 mg4 x 90 mgAt least 1 AE7290817868URTI2125311418Headache161919315Fatigue15535ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 10%Attrition differential high: YesPlacebo13/64 (20%)4%Interleukin-12/23 Monoclonal Antibody 19/256 (7.4%)3%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Leonardi et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZW9uYXJkaTwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+
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ADDIN EN.CITE.DATA 113Year: 2008 and 2009Study name: PHOENIX 1Country: MultinationalQuality rating: FairFUNDING:CentocorRESEARCH OBJECTIVE:Assess the efficacy, quality of life and safety of ustekinumab in patients with moderate-to-severe psoriasis with up to 76 weeks of treatment (cross-over to active treatment at 72 weeks)DESIGN & SIZE: Study design: RCTSetting: MulticenterNumber screened: 984Number eligible: NRNumber enrolled: 766Run-in/Wash-out period:INTERVENTION: Dose: Duration: Sample size:Ustekinumab 4545 mg weeks 0 and 4, thenevery 12 weeks12 weeks255Ustekinumab 9090 mg weeks 0 and 4, thenevery 12 weeks12 weeks256PlaceboNA12 weeks255INCLUSION CRITERIA:18 years or older; a diagnosis of plaque psoriasis for 6 months or longer, a baseline psoriasis area and severity index (PASI) score of 12 or higher, at least 10% body surface area involvement, and candidates for phototherapy or systemic therapy.EXCLUSION CRITERIA:History or symptoms of active tuberculosis; non-plaque forms of psoriasis, recent serious systemic or local infection, known malignancy (except treated basal cell skin cancer or squamous cell skin cancer of at least5 years’ duration), treatment with any agent that specifically targeted interleukins 12 or 23, received biological or investigational agents within the previous 3 months or five drug half-lives, conventional systemic psoriasis treatment or phototherapy within the previous 4 weeks, or topical psoriasis treatment within 2 weeks. OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:See aboveAuthors: Leonardi et al. and Lebwohl et al.Year: 2008 and 2009POPULATION CHARACTERISTICS: Ustekinumab 45Ustekinumab 90PlaceboMean age (years):44.846.244.8Sex (% female):31.432.428.2Ethnicity: NRNRNRClass na?ve:NRNRNROther germane population qualities:Mean PASI20.519.720.4Mean body surface area involvement27.225.227.7Mean duration of psoriasis19.719.620.4Received prior systemic therapy (%)55.355.255.7RESULTS: Primary Outcome Measures: PASI 75Secondary outcomes: PGA, DLQIAt 12 weeksUstekinumab 45Ustekinumab 90PlaceboPASI 50 n (%)213 (83.5%)*220 (85.9%)*26 (10.2%)PASI 75 n (%)171 (67.1%)*170 (66.4%)*8 (3.1%)PASI 90 n (%)106 (41.6%)*94 (36.7%)*5 (2.0%)PASI 100 n (%)32 (12.5%)*28 (10.9%)*0Physicians assessmentCleared47 (18.4%)*`45 (17.6%)*1 (0.4%)Cleared or Minimal154 (60.4%)*158 (61.7%)*10 (3.9%)Change in DLQI (SD)-8.0 (6.87)*-8.7 (6.47)*-0.6 (5.97)Change SF-36 PCS (SD)2.0 (7.4)*3.2 (7.6)*-0.51 (7.5)Change SF-36 MCS (SD)2.1 (9.3)*2.5 (9.5)*-1.3 (7.5)* vs. placebo P < 0.001Authors: Leonardi et al. and Lebwohl et al.Year: 2008 and 2009METHOD OF ADVERSE EVENTS REPORTING: at visitsADVERSE EVENTS (%): at 12 weeksUstekinumab 45Ustekinumab 90PlaceboOverall adverse effects reported:57.651.448.2Infections31.425.926.7URTI7.16.36.3Headache5.55.12.4herpes simplexATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 3%Attrition differential high: NoUstekinumab 450.3%0Ustekinumab 904.3%0.8%Placebo4.7%2.4%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Leonardi, et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZW9uYXJkaTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
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ADDIN EN.CITE.DATA 114Year: 2011Study name: Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet (REACH) Country: US and CanadaQuality rating: FAIRFUNDING:Abbott Laboratories (pharmaceutical industry)RESEARCH OBJECTIVE:To evaluate the efficacy and safety of adalimumab in psoriasis of the hands and/or feetDESIGN & SIZE: Study design: placebo-controlled RCTSetting: multicenterNumber screened: NRNumber eligible: NRNumber enrolled: 81Run-in/Wash-out period: Washout periods of 30 days or 5 half-lives (whichever was longer) were required for biological, systemic, and investigational agents prior to baseline.INTERVENTION: Dose: Duration: Sample size:Adalimumab (ADA)40mg every other week16 weeks49PlaceboNA16 weeks23INCLUSION CRITERIA:Adults 18 years and older diagnosed as having moderate to severe chronic plaque psoriasis of the hands and/or feet for at least 6 months with a Physician’s Global Assessment of the hands and/or feet (hfPGA) score of 3 or higher at baseline and with evidence of psoriatic disease on at least 1 other area of skin outside the hands and/or feet.EXCLUSION CRITERIA:Receipt of prior treatment with adalimumab, diagnosis of palmoplantar pustulosisOTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Psoralen and UV-A phototherapy was not allowed within 4 weeks of baseline; topical therapies on the hands and/or feet (except low- to mid-potency corticosteroids [classes VI and VII]), UV-B phototherapy, and excessive sun exposure or tanning bed use were not allowed within 2 weeks of baseline.Authors: Leonardi, et al.Year: 2011POPULATION CHARACTERISTICS: ADAPlaceboMean age (years):49.054.8Sex (% female):57%65%Ethnicity: 92% white87% whiteClass na?ve:NRNROther germane population qualities:Mean PASI8.85.7Mean body surface area involvement8.9%5.1%Mean duration of psoriasis14.9 years11.5 yearsReceived prior systemic therapy (%)NRNRRESULTS: Primary Outcome Measure: 31% of ADA patients achieved hfPGA score of clear (0) or almost clear (1) compared with 4% of placebo (p=0.01).Secondary Outcome Measures: 51% of ADA patients achieved hfPGA score of clear (0), almost clear (1), or mild (2) compared with 26% of placebo (p=NR).29% of ADA patients achieved >75% improvement in ESIF (ESIF 75) relative to baseline compared with 4% of placebo (p=0.03).43% of ADA patients achieved >50% improvement in ESIF (ESIF 50) relative to baseline compared with 17% of placebo (p=0.04).Mean % improvement in total ESIF score relative to baseline was 41% for ADA patients, compared with 21% for placebo (p=NR).In patients with palmar involvement, mean % improvement in total ESIF score relative to baseline was 47% for ADA patients, compared with 20% for placebo (p=0.01).In patients with plantar involvement, mean % improvement in total ESIF score relative to baseline was 41% for ADA patients, compared with 35% for placebo (p=0.67).In patients with psoriatic nail disease, mean % improvement in total NAPSI relative to baselime was 50% for ADA patients, compared with 8% for placebo (p=0.02)Mean pain score was 26.6 for ADA patients, compared with 43.4 for placebo (p=0.048).In patients with pain score >0 at baseline, mean % improvement in pain score was 31% for ADA patients, compared with 9% for placebo (p=0.39).Authors: Leonardi, et al.Year: 2011METHOD OF ADVERSE EVENTS REPORTING:Laboratory data, physical examinations, and vital signs (and, presumably, patient self-report).ADVERSE EVENTS (%): ADAPlaceboOverall adverse effects reported:63% reported any AE0% reported a serious AE35% reported an infectious AE70% reported any AE4% reported a serious AE44% reported an infectious AEInfectionsOpportunistic only: 2% (oral candidiasis)Opportunistic only: 0%URTINRNRabnormal LFTNRNRherpes simplexNRNRpneumoniaNRNRtbNRNRISRNRNRmalignant diseases0%4% (N=1, breast cancer)serious hepatic events2%0%psoriasis4%9%ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 19.7%Attrition differential high: ? (10%)ADA16%6%Placebo26%9%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Menter et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZW50ZXI8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 116,117Year: 2008 and 2007Country: United States and CanadaFUNDING:Abbott LabsRESEARCH OBJECTIVE:Clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapyDESIGN: Study design: RCTSetting: MulticenterSample size: 1212INTERVENTION: Dose: Duration: Sample size:PlaceboNA16 weeks398Adalimumab80 mg at wk 0 then 40 mg eow16 weeks814drug 3INCLUSION CRITERIA:18 years or older, clinical diagnosis of psoriasis for at least 6 months, stable plaque psoriasis for at least 2 months before screening, moderate to severe plaque psoriasis defined as 10% or more of body surface area affected, a PASI score of 12 or greater, and PGA of at least moderate severity at the baseline.EXCLUSION CRITERIA:history of neurologic symptoms suggestive of central nervous system demyelinating disease or with a history of cancer or lymphoproliferative disease (other than successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix)OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Low- to mid-potency topical corticosteroids applied to the palms, soles, face, and intertriginous areasAuthors: Menter et al. and Revicki et al.Year: 2008, 2007 POPULATION CHARACTERISTICS: Mean age (years):Sex (% female):Ethnicity (% Caucasian): Other germane population qualities: Mean PASIMean body surface area involvementMean duration of psoriasisPrior Systemic therapy: Non-biologic/Biologic (%)Groups similar at baseline: YesPlacebo45.435.490.218.825.618.4 yrs22.1/13.3Adalimumab44.132.991.219.025.818.1 yrs23.1/11.9OUTCOME ASSESSMENT: Primary Outcome Measures: PASI 75 at 16 weeks, % of patients losing an adequate response after week 33 to week 52 and DLQISecondary Outcome Measures: PGA, SF-36Timing of assessments: Baseline and weeks 4,8,12,16,24,33,36,40,44,48,and 52RESULTS:Health Outcome Measures:PASI 75 at 16 weeks Placebo 7% vs. ADA 71% P < 0.001PASI 90 and 100 at 16 weeks Placebo 2% and 1% vs. ADA 45% and 20% P < 0.001PGA, clear or minimal at week 12, Placebo 4% vs. ADA 60% P < 0.001From weeks 33 to 52, patients rerandomized to placebo (28%; 68 of 240) compared with patients rerandomized to adalimumab (5%; 12 of 250) P < 0.001.MeasurePlacebo change from baseline at 16 weeksADA change from baseline at 16 weeksDLQI1.9 (2.6, 1.3)8.4 (8.8, 7.9)P < 0.001SF 36 PCS0.4 (0.5, 1.2)3.7 (3.1, 4.3)P < 0.001SF 36 MCS0.3 (0.7, 1.4)3.8 (3.1, 4.5)P < 0.001Patients global assessment0.4 (0.5, 0.3)1.7 (1.8, 1.6)P < 0.001Authors: Menter et al. and Revicki et al.Year: 2008 and 2007ADVERSE EVENTS %: Overall adverse effects reported:Serious AESerious infectionInfectionMalignincies (not NMSC)NMSCURTINasopharyngitisHeadachePlacebo55.51.81.022.40.30.33.56.53.8Adalimumab62.21.80.628.9 P = 0.0190.20.57.2 P = 0.015.34.9Significant differences in adverse events:In infections and URTI – see aboveANALYSIS: ITT: YesPost randomization exclusions: NoADEQUATE RANDOMIZATION:YesADEQUATE ALLOCATION CONCEALMENT:YesBLINDING OF OUTCOME ASSESSORS:YesATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 74/1212 or 6.1%Attrition differential high: NoPlacebo10.8%1%Adalimumab3.8%1%QUALITY RATING: GoodEvidence Table 7. Targeted Immune Modulators – Plaque Psoriasis STUDY:Authors: Paller et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYWxsZXI8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 120Year: 2008, 2010, 2011Country: US and CanadaQuality rating: FairFUNDING:Immunex, a wholly owned subsidiary of Amgen, and by Wyeth Pharmaceuticals. RESEARCH OBJECTIVE:Assess the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.DESIGN & SIZE: Study design: RCT Setting: Multicenter Sample size: 211; 138 in withdrawal-retreatment phaseINTERVENTION: Dose: Duration: Sample size:Withdrawal-retreatment period:Dose: Duration: Sample size:Etanercept0.8 mg per kg12 weeks106EtanerceptMax 50 mg for weights ≥62 kg12 weeks69PlaceboNA12 weeks105PlaceboNA12 weeks69INCLUSION CRITERIA:4 to 17 years; stable, moderate-to-severe plaque psoriasis at screening, defined as a psoriasis area-andseverity index (PASI) score of at least 12), a static physician’s global assessment of at least 3 (where 0 indicates clear and 5 severe psoriasis), and psoriasis involvement of at least 10% of the BSA; a history of psoriasis for at least 6 months; and previous or current treatment with phototherapy or systemic psoriasis therapy (e.g., methotrexate, cyclosporine, or retinoids) or psoriasis considered by the investigator as poorly controlled with topical therapy.EXCLUSION CRITERIA:Pregnancy or lactation (sexually active patients were required to use contraception); guttate, erythrodermic, or pustular psoriasis; other skin conditions that would interfere with study evaluations; previous treatment with anti-TNF agents; major concurrent medical conditions; treatment with psoralen and ultraviolet A (PUVA), ultraviolet A, ultraviolet B, systemic psoriasis medications, oral or parenteral corticosteroids, topical corticosteroids, topical vitamin A or D analogue preparations, anthralin, or calcineurin inhibitor within a 14-day washout period before the study; and treatment with biologic agents within a 30-day washout periodOTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Low-to-moderate-potency topical steroids on the scalp, axillae, or groin.Authors: Paller et al. and Siegfried et al. and Langley et al.Year: 2008, 2010, 2011POPULATION CHARACTERISTICS: Groups similar at baselineEtanerceptPlaceboWithdrawal-Retreatment PeriodMean age (years):141313 (median)Sex (% female):485051Ethnicity: 78% white71% white78% whiteOther germane population qualities:Mean PASI16.716.416.7 (median)Mean body surface area involvement21.020.020.5 (median)Mean duration of psoriasis6.8 years5.8 years5.8 years (median)Received prior systemic therapy (%)555957OUTCOME ASSESSMENT:Primary Outcome Measures: PASI 75 at week 12Secondary Outcome Measures: PASI 50 and 90, physicians global assessment of clear or almost clear, Children’s Dermatology Life Quality IndexTiming of assessments: Baseline weeks 2 ,4, 6, 8, 12, 16 and every 4 weeksFollowing the 12 week double-blind period, all patients received open-label etanercept for 24 weeks. At the end of this period, patients who received 75% improvement in PASI response from baseline (PASI 75) were re-randomized to a 12-week, double-blind withdrawal-treatment period. During this phase, patients received either placebo or etanercept as long as they maintained a clinical response, defined as PASI 75. Patients whose response fell below PASI 75 were retreated with etanercept in an open-label fashion until study completion. PASI 75 was assessed every 4 weeks during the 12-week, double-blind withdrawal-retreatment period.RESULTS: Health Outcome Measures at 12 weeks:? PASI 75: etanercept 57% vs. placebo 11%, p<0.001? PASI 50: etanercept 75% vs. placebo 23%, p<0.001? PASI 90: etanercept 27% vs. placebo 7%, p<0.001? Physicians global assessment of clear or almost clear: etanercept 53% vs. placebo 13%, p<0.001? CDLQI mean improvement: etanercept 52% vs. placebo 18%Withdrawal-Retreatment period: Etanercept (received etanercept throughout withdrawal-retreatment) vs. Placebo (received placebo in withdrawal phase) vs. Placebo (received etanercept in retreatment phase)? Percentage of patients who achieved PASI 75 at:Week 40: 81% vs. 75% vs. N/AWeek 44: 82% vs. 76% vs. 27%Week 48: 80% vs. 85% vs. 36%? Percentage of patients who achieved PGA clear/almost clear at:Week 40: 69% vs. 60% vs N/AWeek 44: 65% vs. 57% vs 33%Week 48: 58% vs. 68% vs 29%? In the group treated with blinded or open-label etanercept, 80% patients maintained or regained PASI 75 at the end of the 12-week period. In all, 70% patients on blinded etanercept maintained PASI 75 at every study visit during the 12-week period, compared with 54% patients who did so on blinded placebo.? At the time the 29 patients on placebo began receiving etanercept retreatment, their mean improvementfrom baseline in the PASI response had decreased to 47.4%. After 4 to 8 weeks of retreatment, their mean improvement from baseline in the PASI response was 64.4%.? Of the 137 patients who completed the 12-week period, 95 (69%) remained on blinded placebo or blinded etanercept for the 12-week period. In the placebo group, 40/69 (58%) patients remained on blinded placebo throughout the period, and 29/69 (42%) received etanercept retreatment. In the etanercept group, 55/68 (81%) patients remained on blinded etanercept. The remaining 13 (19%) patients on etanercept entered the open-label retreatment phase, although one patient entered without losing PASI 75. Authors: Paller et al. and Siegfried et al. and Langley et al.Year: 2008, 2010, 2011ADVERSE EVENTS:EtanerceptPlaceboOverall adverse effects reported (event rates per 100 pt/yrs:554.5765.4URTI54.669.1HeadacheNasophyrantgitis32.831.595.753.2Influenza14.015.9Streprococcal pharygitis13.35.3Cough12.110.6Pharyngolaryneal pain12.131.9Vomiting12.110.6Nasal congestion10.315.9Skin papilloma9.70Overall adverse effects reported:Double-blind withdrawal phase:Double-blind withdrawal phase:Open-label retreatment phase:EtanerceptOverall adverse effects52.9%46.4%42.9%At least 1 serious AE0%0%0%Headache8.8%2.9%NRNasophyrantgitis 10.3%2.9%NRURTINRNR14.3%SinitiusNRNR7.1%Injection site reaction1.5%1.4%2.4%ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 3 (plus 1 in withdrawal-retreatment phase)Attrition differential high: NoEtanercept2%0%Placebo1%1%URTI: upper respiratory tract infection. Evidence Table 7. 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ADDIN EN.CITE.DATA 121Year: 2008Study name: PHOENIX 2Country: MultinationalQuality rating: GoodFUNDING:CentocorRESEARCH OBJECTIVE:Assess the efficacy and safety of ustekinumab in patients with moderate-to-severe psoriasis with up to 52 weeks of treatment.DESIGN & SIZE: Study design: RCTSetting: MulticenterNumber screened: 1568Number eligible: NRNumber enrolled: 1230Run-in/Wash-out period: NoINTERVENTION: Dose: Duration: Sample size:Ustekinumab 4545 mg weeks 0 and 4, thenevery 12 weeks12 weeks409Ustekinumab 9090 mg weeks 0 and 4, thenevery 12 weeks12 weeks411PlaceboNA12 weeks410INCLUSION CRITERIA:18 years or older; a diagnosis of plaque psoriasis for 6 months or longer, a baseline psoriasis area and severity index (PASI) score of 12 or higher, at least 10% body surface area involvement, and candidates for phototherapy or systemic therapy.EXCLUSION CRITERIA: History or symptoms of active tuberculosis; non-plaque forms of psoriasis, recent serious systemic or local infection, known malignancy (except treated basal cell skin cancer or squamous cell skin cancer of at least5 years’ duration), treatment with any agent that specifically targeted interleukins 12 or 23, received biological or investigational agents within the previous 3 months or fi ve drug half-lives, conventional systemic psoriasis treatment or phototherapy within the previous 4 weeks, or topical psoriasis treatment within 2 weeks OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:See aboveAuthors: Papp et al.Year: 2008POPULATION CHARACTERISTICS: Ustekinumab 45Ustekinumab 90PlaceboMean age (years):45.146.647.0Sex (% female):30.832.331.0Ethnicity: NRNRNRClass na?ve:61.663.561.2Other germane population qualities:Mean PASI19.420.119.4Mean body surface area involvement25.927.126.1Mean duration of psoriasis19.320.320.8Received prior systemic therapy (%)54.554.558.8RESULTS: Primary Outcome Measures: PASI 75Secondary outcomes: PGA, DLQIAt 12 weeksUstekinumab 45Ustekinumab 90PlaceboPASI 50 n (%)342 (83.6%)*367 (89.3%)*41 (10.0%)PASI 75 n (%)273 (66.7%)*311 (75.7%)*15 (3.7%)PASI 90 n (%)173 (42.3%)*209 (50.9%)*3 (0.7%)PASI 100 n (%)74 (18.1%)*75 (18.2%)*0Physicians assessmentCleared93 (22.7%)* 115 (28.0%)*0Cleared or Minimal278 (68.0%)*302 (73.5%)*20 (4.9%)Change in DLQI-9.3 (7.12)*-10.0 (6.67)*-0.5 (5.66)* vs placebo P < 0.001Authors: Papp et al. Year: 2008METHOD OF ADVERSE EVENTS REPORTING: at visitsADVERSE EVENTS (%): Ustekinumab 45Ustekinumab 90PlaceboOverall adverse effects reported:53.147.949.8infections21.522.420.0Arthralgia3.42.42.9Cough0.71.01.7Headache4.64.64.1URTI4.42.93.4Nasopharyngitis7.36.87.1ISR1.51.50.2ATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 2.6%Attrition differential high: noUstekinumab 451.4%0.5%Ustekinumab 902.2%1.2%Placebo4.3%2.0%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Reich et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWljaDwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 122-124Year: 2005 and 2006 and 2007Country: NRFUNDING:Centocor and Schering-PloughRESEARCH OBJECTIVE:To present the results of a phase III study, addressing the long-term safety, efficacy and productivity of infliximab for the treatment of skin and nail lesions in patients with psoriasisDESIGN: Study design: RCT Setting: MulticenterSample size: 378 INTERVENTION: Dose: Duration: Sample size:Placebo / INFN/A, then 5 mg/kg (wk 0,2,6,14,22)22 weeks, then 24 weeks (total 46)77INF5 mg/kg (wk 0,2,6, then every 8 wks)46 weeks301INCLUSION CRITERIA:Patients diagnosed with moderate to severe plaque psoriasis for > 6 months; candidates for phototherapy or systemic therapy; PASI of > 12 and > 10% of their total body surface area affected by psoriasis.EXCLUSION CRITERIA:History or risk of serious infection, lymphoproliferative disease, or active TB; previous treatment with INF or any other TNF?-antagonist was allowed.OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:2.5% hydrocortisone, or equivalent, applied topically to face, groin, or both, after week 10.Authors: Reich et al.Year: 2005 and 2006 and 2007POPULATION CHARACTERISTICS: Mean age (years):Sex (% female):Ethnicity: Other germane population qualities: Psoriasis duration (yrs)Body surface area (%)PASIPatients with nail psoriasis (%)MTX use (%)Groups similar at baseline: YesDisease severity: Moderate-to-severePlacebo43.821NR17.31822.88646INF42.631NR19.11922.98142OUTCOME ASSESSMENT: Primary Outcome Measures: PASI 75 (> 75% improvement in baseline PASI) at week 10 and Quality of life DLQI and SF-36, 10-cm productivity visual analog scale (VAS), role-physical and role-emotional domain scores of the Short Form 36-Item questionnaire (SF-36).Secondary Outcome Measures: PASI 75 at week 24; PGA of cleared or minimal at week 10, 24, and 50; PASI 50; PASI 90; NAPSI at weeks 10, 24, and 50.Timing of assessments: NRRESULTS:Health Outcome Measures:At week 24, PASI 75 achieved by 82% (INF) vs. 4% (placebo) (P < 0.0001)The % improvement in the NAPSI was significantly greater in INF-treated patients than placebo at weeks 10 and 24.Improvement from baselineAt week 24, DLQI INF 10.0 vs. placebo 0.2 (P < 0.001)At week 24, SF-36 PCS INF 4.9 vs. placebo -1.4 (P < 0.001)At week 24, SF-MCS INF 5.3 vs. placebo -0.5 (P < 0.001)At week 24, Productivity VAS, INF – 0.2 ± 3.2 vs. placebo 2.5 ± 3.5 (P < 0.001)At week 24, PGA response INF 74 vs. placebo 3%, (P < 0.0001)Intermediate Outcome Measures:6% and 2% of patients in INF group had asymptomatic increases in alanine aminotransferase and aspartate aminotransferase, respectively.Fewer antibody-positive patients achieved PASI 75.Authors: Reich et al.Year: 2005 and 2006 and 2007ADVERSE EVENTS: Overall adverse effects reported (%)URTIHeadachePainPsoriasisSevere adverse eventInfectionsNeoplasmsPlacebo/INF16125133400INF1514636421Significant differences in adverse events:NoANALYSIS: ITT: YesPost randomization exclusions: NRADEQUATE RANDOMIZATION:YesADEQUATE ALLOCATION CONCEALMENT:YesBLINDING OF OUTCOME ASSESSORS:YesATTRITION %(overall):ATTRITION (treatment specific):Loss to follow-up: Withdrawals due to adverse events: Overall loss to follow-up: 17.5% (24 weeks)Loss to follow-up differential high: NoPlacebo/INF31.2NRINF30.1NRQUALITY RATING: GoodEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Reich et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWljaDwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 126Year: 2009, 2008Study name: - Country: Europe (9 countries)Quality rating: FAIRFUNDING:Wyeth Research (pharmaceutical industry)RESEARCH OBJECTIVE:To assess baseline patient-reported outcomes (PROs) and PRO improvement in patients with psoriasis administered 50 mg once weekly.DESIGN & SIZE: Study design: placebo-controlled RCTSetting: unclearNumber screened: 161Number eligible: 143Number enrolled: 142Run-in/Wash-out period: noneINTERVENTION: Dose: Duration: Sample size:ETA50mg once a week (QW)12 weeks96PlaceboN/A12 weeks46INCLUSION CRITERIA:Clinically stable plaque psoriasis involving ≥10% of body surface area; minimum PASI score of 10 (moderate-to-severe); failed to respond to, had a contradiction for or were intolerant of ≥1 systemic treatment or phototherapy at an adequate dose of sufficient duration.EXCLUSION CRITERIA: Patients with active guttate, erythrodermic or pustular psoriasis at the time of screening, or other active skin conditions that would interfere with study evaluations, were excluded. Patients were also ineligible if they had a serious infection within 1 month of study screening or the baseline visit or a body mass index (BMI) greater than 38 kg m2. Patients were not to have received etanercept, an antibody to TNF, or other TNF inhibitors at any time; alefacept, efalizumab, anti-CD4 agents, or diphtheria interleukin-2 fusion protein within the previous 6 months; ultraviolet A or B phototherapy, psoralen and ultraviolet A phototherapy, systemic psoriasis therapy (methotrexate, ciclosporin, acitretin or fumarates), or oral or parenteral corticosteroids within the previous month; or topical corticosteroids in high strengths, topical vitamin A or D analogue preparations, dithranol or topical calcineurin inhibitors (pimecrolimus or tacrolimus) within the previous 2 weeks.OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Patients were permitted to use only topical corticosteroids of low to moderate strength on the scalp, axillae and groin during the study. Topical corticosteroids were not allowed on other areas, including the hands and feet. Doses of topical corticosteroids were to remain stable for at least 2 weeks before the baseline visit until the end of the double-blind period.Authors: Reich et al. and van de Kerkhof et al.Year: 2009, 2008POPULATION CHARACTERISTICS: ETAPlaceboFull SampleMean age (years):45.943.644.7Sex (% female):38.5%45.6%42%Ethnicity: NRNRNRClass na?ve:100%100%100%Other germane population qualities:Mean PASI21.421.021.2Mean body surface area involvement26.5%30.3%28.4Mean duration of psoriasis19.3 years17.3 years18.3 yearsReceived prior systemic therapy (%)49.0% (failed ≥1)47.8% (failed ≥1)NRRESULTS: Primary Outcome Measures: 37.5% of ETA patients had ≥75% improvement on the PASI, compared with 2.2% of placebo (p<0.0001);ETA patients had a mean decrease in DLQI of 7.4 compared with placebo (-1.2); P<0.0001;ETA patients had a mean increase in EQ-5D utility score of 0.12 compared with placebo (+0.02); P<0.05;ETA patients had a mean change in EQ-5D VAS score of +6.8 compared with placebo (-4.9); P<0.01;Secondary Outcome Measures: 19.8% of ETA patients and 50.0% of placebo patients had DLQI ≥11;29.2% of ETA patients and 15.2% of placebo patients achieved DLQI of 0 or 1;74.7% of ETA patients and 28.6% of placebo patients achieved improvement of ≥5 points on DLQI; P<0.0001;Mean DLQI score: ETA = 5.8 vs. placebo = 12.3; P<0.0001;Mean EQ-5D utility score: ETA = 0.81 vs. placebo = 0.69;Mean FACIT-F score (change from baseline): ETA = 40.7 (+1.3) vs. placebo = 39.5 (+0.3); no significant difference;9.4% fewer ETA patients reported mobility problems, compared with no fewer placebo patients (P<0.05);10.4% fewer ETA patients reported anxiety/depression, compared with 4.4% fewer placebo patients (P<0.05);26% fewer ETA patients reported pain discomfort, compared with 13% fewer placebo patients (P<0.05);14.5% fewer ETA patients reported problems with usual activities, compared with 2.1% more placebo patients, NSD;7.2% fewer ETA patients reported problems with self-care, compared with 4.4% fewer placebo patients, NSD.Authors: Reich et al. and van de Kerkhof et al.Year: 2009, 2008METHOD OF ADVERSE EVENTS REPORTING:NRADVERSE EVENTS (%): ETAPlaceboOverall adverse effects reported:NRNRInfectionsNRNRURTINRNRabnormal LFTNRNRherpes simplexNRNRpneumoniaNRNRtbNRNRISRNRNRATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 11%Attrition differential high: Yes ETA6%3.1%Placebo22%6.5%URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosisEvidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY:Authors: Saurat et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYXVyYXQ8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 128Year: 2007, 2008Country: MultinationalFUNDING:Abbott LabsRESEARCH OBJECTIVE:Compare a biologic agent ADA with MTX, a traditional systemic agent, to define clearly the role of biologics in psoriasisDESIGN: Study design: RCTSetting: MulticenterSample size: 271INTERVENTION: Dose: Duration: Sample size:PlaceboNA16 weeks53Methotrexate7.5 to 25 mg weekly16 weeks110Adalimumab80 mg load then 40 mg eow16 weeks108INCLUSION CRITERIA:>18 years of age with moderate to severe psoriasis, plaque psoriasis for at least 1 year and stable plaque psoriasis for at least 2 months, candidates for systemic therapy or phototherapy and to have had active psoriasis despite treatment with topical agents, naive to both TNF-antagonist therapy and methotrexate.EXCLUSION CRITERIA:History of clinically significant haematological, renal or liver disease ?abnormal laboratory values; with a history of demyelinating disease, cancer, or other lymphoproliferative disease (other than successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and ?or localized carcinoma in situ of the cervix); or who were immunocompromised.OTHER MEDICATIONS/ INTERVENTIONS ALLOWED:Shampoos free of corticosteroids; bland emollients; and low-potency topical corticosteroids for the palms, soles, face, inframammary areas and groin only, not used within 24 h of a study visitAuthors: Saurat et al. and Revicki et al.Year: 2007, 2007POPULATION CHARACTERISTICS: Mean age (years):Sex (% female):Ethnicity (% Caucasian): Other germane population qualities: Mean PASIMean body surface area involvementMean duration of psoriasisReceived prior systemic therapy and/or phototherapy (%)Groups similar at baseline: YesPlacebo40.73492.519.228.418.890.4Methotrexate41.633.695.519.432.418.987.2Adalimumab42.935.295.420.233.617.982.2OUTCOME ASSESSMENT: Primary Outcome Measures: PASI 75 at week 16 and DLQISecondary Outcome Measures: PASI 50, 90 and 100, and PGA and EuroQOL5DTiming of assessments: baseline and at weeks 1, 2, 4, 8, 12 and 16.RESULTS:Health Outcome Measures at 16 weeks:PASI 75 ADA 79.6% vs. 35.5% MTX vs. Placebo 18.9% PASI 100 ADA 16.7% vs. MTX 7.3% vs. placebo 1.9 P = .004DLQI change from baseline (95% CI) ADA 9.1 (-10.4 to -7.8) vs. MTX-5.7 (-6.8 to -4.5) vs. placebo -3.4 (-5.2 to -1.6) ADA vs. placebo P < 0.001EQ 5D Index Score change from baseline (95% CI) ADA 0.2 (0.2 to 0.3) vs. MTX 0.1 (0.1 to 0.2) vs. placebo 0.1 (0.0 to 0.2) EQ-5D VAS change from baseline (95% CI) ADA 21.4 (16.6 to 26.3) vs. MTX 11.5 (6.5 to 16.5) vs5.7 (-1.4 to 12.8)PGA ADA -1.6 vs. placebo -0.5 P < 0.001Authors: Saurat et al. and Revicki et al.Year: 2007, 2008ADVERSE EVENTS %: Overall adverse effects reported:Serious AEsInfections (non-serious)Serious infectionsNasopharyngitisHeadachePruritusRhinitisNauseaRhinorrheaViral InfectionArthralgiaPlacebo79.21.943.4020.89.411.37.57.55.71.91.9Methotrexate81.80.941.8023.610.91.83.67.305.54.5Adalimumab73.81.947.7028.013.13.72.83.72.805.6Significant differences in adverse events:NoANALYSIS: ITT: YesPost randomization exclusions: NoADEQUATE RANDOMIZATION:YesADEQUATE ALLOCATION CONCEALMENT:YesBLINDING OF OUTCOME ASSESSORS:YesATTRITION (overall):ATTRITION (treatment specific):Attrition overall: Attrition due to adverse events: Overall attrition: 15 (5.5%)Attrition differential high: NoPlacebo9.4%<1%Methotrexate5.5%5.5%Adalimumab3.7%1%QUALITY RATING: Good ................
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