Alopeciaareata:targetedreviewofadverseeventsassociatedwithclinicalstudiesoftreatments
Background&Objectives
Alopeciaareata(AA)isacommonautoimmunediseasecharacterizedbysuddenpatchy hairlossinthescalp,eyebrows,andeyelashes¹.AAmaypresentatanyageandcanleadto emotionaldistressandreducedqualityoflife(QoL)².Arangeoftreatmentsareavailable forthemanagementofAA,howevertheevidencefortheirefficacyisvariable³.Additionally, assessmentofadverseevents(AEs)insomeclinicallycontrolledstudiesremains insufficientlyestablished,therebypotentiallycompromisingthesafetyprofilesof treatments⁴.ThistargetedreviewaimedtoquantifythemostfrequentlyreportedAEsin clinicalstudies,includingrandomizedcontrolledtrials(RCTs)andotherprospective randomizedstudiesforthetreatmentofAA.
Methods
Studypublicationsfromthelast15years(January1,2008toDecember31,2022)were identifiedthroughtargetedsearchesofthePubMeddatabaseandGoogleScholar. InclusioncriteriaincludedclinicalstudiesintheEnglishlanguagethatevaluatedadverse eventsassociatedwithAAtreatment.
Studytitlesandabstractswerescreened,thenstudydesigndetailsanddataonAEsbytype oftreatmentwereextractedandcheckedforaccuracybytwoindependentreviewers. Bothsystemicandtopicaltreatmentswereconsidered.Thefivemostfrequentlyreported AEsbyparticipantsreceivingtreatmentwererecordedforanalysis.
Results
SixteenclinicalstudiesreportingAEsassociatedwithfourtopicaland12systemictherapies usedinthetreatmentofAAwereincluded(see Table1).Ofthe16clinicalstudiesincluded, 15wereRCTs,andonewasaprospectiverandomizedstudy.
Table1: Overviewofstudiesincludedinthereview
Discussion&Conclusions
Presently,systemicandtopicalAAtreatmentoptionsarelimitedandassociatedwith highratesofAEs-particularlyofadermatologicalorrespiratorynature-whichhave thepotentialtocompromisetheirlong-termefficacyandoverallsafetyprofile.
Thefindingsofthistargetedreviewhighlightthefollowingkeypoints:
● TreatmentsforAAareassociatedwithhighratesofAEs,andthereisanevident needfortherapieswithimprovedsafetyprofiles.Tothiseffect,conductingboth RCTsandreal-worldstudiestoassesstheefficacyandsafetyprofilesof therapiesinacontrolledenvironmentandinroutineclinicalpracticeisof paramountimportance.Thesestudiesshouldfocusonthecompleteand transparentreportingofAEdata,particularlyasdetailedpublishedliteraturein thisarearemainsscarce⁵
● FewpublicationscommentedontheimpactofAEsonhealth-relatedQoL (HRQol),animportantfactorforpatientswithAA²,norfocusedonthe collectionofpatient-reportedadverseevents,bothofwhichshouldbe consideredwhenbuildingafullpictureoftreatmentsafety.
● Futurereviewscouldfocusonpublicationsrelatingtothepatientexperienceof AEsaswellastheirimpactonHRQoLtoshedlightontheAEsofgreatest importancetopatients,theirtreatmentpreferences,andtoidentifyfurther gapsinknowledgeorunmetneedsinAAmanagement.Findingscouldbeused toinformfutureclinicalstudydesigninvolvingthecollectionofAEdata.
References
¹PaggioliI,MossJ.AlopeciaAreata:CasereportandreviewofpathophysiologyandtreatmentwithJak inhibitors. JAutoimmun.2022;133:102926.doi:10.1016/j.jaut.2022.102926
²AbediniR,HallajiZ,LajevardiV,NasimiM,KhalediMK,TohidinikHR.Qualityoflifeinmildandseverealopecia areatapatients.IntJWomen'sDermatology.2018;4(2):91-94.doi:10.1016/j.ijwd.2017.07.001
³DarwinE,HirtPA,FertigR,DolinerB,DelcantoG,JimenezJJ.AlopeciaAreata:ReviewofEpidemiology, ClinicalFeatures,Pathogenesis,andNewTreatmentOptions. IntJTrichology.2018;10(2):51-60.doi:10.4103/ ijt.ijt_99_17
Figure1: Totalnumberoftoptenadverseevents(AEs)reportedacrossthestudiesreviewed
URTI:upperrespiratorytractinfection
¹Inclusiveof12participantsfromaninitialopen-labelphaseasthereportedAEswerenotseparatedbyphase.
²Inclusiveof15participantswhoreceivedaplacebobeforeswitchingtotreatmentasthereportedAEswerenotseparatedbysubgroups.
Atotalof35AEswererecorded.Asshownin Figure1,themostfrequentlyreportedAEsoverallwere headaches(n=213),nasopharyngitis(n=189),upperrespiratorytractinfections(URTIs;n=188),acne (n=151),andfolliculitis(n=49).TwoofthefivemostfrequentlyreportedAEsweredermatologicaland twowererespiratory.ThemostfrequentlyreportedAEsassociatedwithsystemictreatmentswere headaches,URTIs,andnasopharyngitis,whilefortopicaltreatmentstheywereheadaches, nasopharyngitis,andpruritus,inorderoffrequency.
⁴Renert-YuvalY,Guttman-YasskyE.TheChangingLandscapeofAlopeciaAreata:TheTherapeutic Paradigm. AdvTher.2017;34(7):1594-1609.doi:10.1007/s12325-017-0542-7
⁵AlsantaliA.Alopeciaareata:anewtreatmentplan. ClinCosmetInvestigDermatol.2011;4:107-115. doi:10.2147/CCID.S22767
