Off-Label Biologic Regimens in Psoriasis A Systematic Review of Efficacy and Safety of Dose Escalation, Reduction, and Interrupted Biologic Therapy 英文参考文献.docVIP

Off-LabelBiologicRegimensinPsoriasis:ASystematic ReviewofEfficacyandSafetyofDoseEscalation, Reduction,andInterruptedBiologicTherapy ElizabethA.Brezinski2,AprilW.Armstrong1* 1Department of Dermatology, University of California Davis, Sacramento, California, United States of America, 2School of Medicine, University of California Davis, Sacramento,California,UnitedStatesofAmerica Abstract Objectives: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic reviewexiststodatethatsynthesizestheefficacyandsafetyoftheseoff-labeldosingregimens.Theaimofthissystematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment)withetanercept,adalimumab,infliximab,ustekinumab,andalefaceptforpsoriasistreatment. Data Sources and Study Selection: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospectiveclinicaltrialsthatstudiedbiologictherapyforpsoriasistreatmentinadults.Individualarticleswerescreenedfor studiesthatexaminedescalated,reduced,orinterruptedtherapywithetanercept,adalimumab,infliximab,ustekinumab,or alefacept. DataSynthesis:Atotalof23articleswith12,617patientsmatchedtheinclusionandexclusioncriteriaforthesystematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non- responders,doseescalationwithetanercept,adalimumab,ustekinumab,andalefacepttypicallyresultedingreaterefficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial responseratesformostbiologics.