Background:Interleukin(IL)-1inhibitorshavebeensuggestedaspossibletherapeuticoptionsinalargenumberofoldandnewclinicalentitiescharacterizedbyanIL-1drivenpathogenesis. Vitaleetal. Interleukin(IL)-1InhibitioninAutoinflammatoryandAutoimmuneDisorders Objectives:Toperformanationwidesnapshotoftheon-labelandoff-labeluseofanakinra(ANA)andcanakinumab(CAN)fordifferentconditionsbothinchildrenandadults.Methods:Weretrospectivelycollecteddemographic,clinical,andtherapeuticdatafrombothadultandpediatricpatientstreatedwithIL-1inhibitorsfromJanuary2008toJuly2016.Results:Fivehundredandtwenty-sixtreatmentcoursesgivento475patients(195males,280females;111childrenand364adults)wereevaluated.ANAwasadministeredin421(80.04%)courses,CANin105(19.96%).Sixty-two(32.1%)patientshadbeentreatedwithbothagents.IL-1inhibitorswereemployedin38differentindications(37withANA,16withCAN).Off-labelusewasmorefrequentforANAthanCAN(p<0.0001).ANAwasemployedasfirst-linebiologicapproachin323(76.7%)cases,whileCANin37cases(35.2%).IL-1inhibitorswereassociatedwithcorticosteroidsin285(54.18%)coursesanddiseasemodifyinganti-rheumaticdrugs(DMARDs)in156(29.65%).ANAdosagerangedfrom30to200mg/day(or1.0–2.0mg/kg/day)amongadultsand2–4mg/kg/dayamongchildren;regardingCAN,themostfrequentlyusedposologieswere150mgevery8weeks,150mgevery4weeksand150mgevery6weeks.ThefrequencyoffailurewashigheramongpatientstreatedwithANAatadosageof100mg/daythanthosetreatedwith2mg/kg/day(p=0.03).Seventy-sixpatients(14.4%)reportedanadverseevent(AE)and10(1.9%)asevereAE.AEsoccurredmorefrequentlyaftertheageof65comparedtobothchildrenandpatientsagedbetween16and65(p=0.003andp=0.03,respectively).Conclusions:IL-1inhibitorsaremostlyusedoff-label,especiallyANA,duringadulthood.ThehighfrequencyofgoodclinicalresponsessuggeststhatIL-1inhibitorsareusedwithawarenessofpathogeneticmechanisms;adulthealthcarephysiciansgenerallyemploystandarddosages,whilepediatriciansaremoreproneinusingaweight-basedposology.Doseadjustmentsandswitchingbetweendifferentagentsshowedtobeeffectivetreatmentstrategies.OurdataconfirmthegoodsafetyprofileofIL-1inhibitors.
A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists: A nationwide multi-center retrospective observational study
Gallizzi, Romina;
2016-01-01
Abstract
Background:Interleukin(IL)-1inhibitorshavebeensuggestedaspossibletherapeuticoptionsinalargenumberofoldandnewclinicalentitiescharacterizedbyanIL-1drivenpathogenesis. Vitaleetal. Interleukin(IL)-1InhibitioninAutoinflammatoryandAutoimmuneDisorders Objectives:Toperformanationwidesnapshotoftheon-labelandoff-labeluseofanakinra(ANA)andcanakinumab(CAN)fordifferentconditionsbothinchildrenandadults.Methods:Weretrospectivelycollecteddemographic,clinical,andtherapeuticdatafrombothadultandpediatricpatientstreatedwithIL-1inhibitorsfromJanuary2008toJuly2016.Results:Fivehundredandtwenty-sixtreatmentcoursesgivento475patients(195males,280females;111childrenand364adults)wereevaluated.ANAwasadministeredin421(80.04%)courses,CANin105(19.96%).Sixty-two(32.1%)patientshadbeentreatedwithbothagents.IL-1inhibitorswereemployedin38differentindications(37withANA,16withCAN).Off-labelusewasmorefrequentforANAthanCAN(p<0.0001).ANAwasemployedasfirst-linebiologicapproachin323(76.7%)cases,whileCANin37cases(35.2%).IL-1inhibitorswereassociatedwithcorticosteroidsin285(54.18%)coursesanddiseasemodifyinganti-rheumaticdrugs(DMARDs)in156(29.65%).ANAdosagerangedfrom30to200mg/day(or1.0–2.0mg/kg/day)amongadultsand2–4mg/kg/dayamongchildren;regardingCAN,themostfrequentlyusedposologieswere150mgevery8weeks,150mgevery4weeksand150mgevery6weeks.ThefrequencyoffailurewashigheramongpatientstreatedwithANAatadosageof100mg/daythanthosetreatedwith2mg/kg/day(p=0.03).Seventy-sixpatients(14.4%)reportedanadverseevent(AE)and10(1.9%)asevereAE.AEsoccurredmorefrequentlyaftertheageof65comparedtobothchildrenandpatientsagedbetween16and65(p=0.003andp=0.03,respectively).Conclusions:IL-1inhibitorsaremostlyusedoff-label,especiallyANA,duringadulthood.ThehighfrequencyofgoodclinicalresponsessuggeststhatIL-1inhibitorsareusedwithawarenessofpathogeneticmechanisms;adulthealthcarephysiciansgenerallyemploystandarddosages,whilepediatriciansaremoreproneinusingaweight-basedposology.Doseadjustmentsandswitchingbetweendifferentagentsshowedtobeeffectivetreatmentstrategies.OurdataconfirmthegoodsafetyprofileofIL-1inhibitors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
