Title:Matrix-Inducedautologouschondrocyteimplantationandautologouschondrocyte Implantation

Title:Matrix-inducedautologouschondrocyteimplantationandautologouschondrocyte implantation

Agency:MedicalServicesAdvisoryCommittee(MSAC) MDP853

CommonwealthDepartmentofHealthandAgeing GPOBox9848CanberraACT2601

Reference:MSACApplication1140

Firstprinted

ISBN(print)978-1-74241-400-0ISBN(online) 978-1-74241-401-0

Aim

Toassessthesafety,effectivenessandcost-effectivenessofmatrix-inducedautologouschondrocyte implantation(MACI)andautologouschondrocyteimplantation(ACI)forthetreatmentofarticularcartilage defects.

ResultsandConclusions

Safety

Atotalof53studieswereidentifiedforinclusionintheassessmentofthesafetyofMACIandACI.This included10comparativestudies,fourcomparativestudiesthatweretreatedascaseseries,and39caseseries. ComparativestudiescomparedMACIorACIwithmicrofracture,mosaicplastyordebridement.Samplesizes rangedfrom10to309patients,withsafetydatareportedforanoveralltotalof3,254patients.

Forthemajorityofadverseeventsreported,therewerenoobviousdifferencesinincidenceratesbetweenthe MACI/ACIandcomparatorproceduregroups.Howeveronestudyreportedthattheincidenceofjoint swellingandjointcrepitationwassignificantlyhigherfollowingACIcomparedwithmicrofracture.

Similarly,theincidenceratesforjointeffusionandtissuehypertrophy(bothsymptomaticandasymptomatic) appearedhigherfollowingMACI/ACIthanfollowingcomparatorprocedures.Procedurefailureratewasthe mostcommonlyreportedadverseevent,anddemonstratedanincidencerateof9.5percentintheMACI/ACI population,and11.9percentinthecomparatorprocedurepopulation.Majoradverseeventssuchasjoint infectionanddeepveinthrombosiswererareinboththeMACI/ACIandcomparatorgroups,andtherewere noreporteddeathsasaresultoftheproceduresineithergroup.

Overall,thesafetyofMACI/ACIappearstobecomparabletothosecomparatorproceduresevaluatedinthis assessment.

Effectiveness

Atotalof14comparativestudieswereidentifiedandincludedtoinformontheeffectivenessofMACIand ACI.Atotaloffiverandomisedcontrolledtrials(RCTs)comparedMACIorACItomicrofracture(three studies)ormosaicplasty(twostudies),whileonepseudo-RCTcomparedACItomosaicplasty.Eightnon- randomisedcomparativestudiescomparedMACIorACItomicrofracture(fivestudies),mosaicplasty(two studies)ordebridement(onestudy).

Functionaloutcomeswerethefocusofthemajorityofincludedstudies;however,anumberofstudiesalso reportedimagingoutcomesfollowingMACI/ACIandcomparatorprocedures.

Avarietyofscoringsystemswereusedtoassesskneefunction,whichmadeitdifficulttodrawdirect comparisonsbetweenthedifferentproceduresacrossstudies.Themostcommonlyreportedfunctional outcomemeasuresweretheLysholmandTegnerscores.OftheeightstudiesthatreportedLysholmscores, sixreportednosignificantdifferenceintheeffectivenessofMACI/ACIovertimecomparedwithcomparator procedures;however,onestudyeachreportedthatMACI/ACIwasmoreeffectiveovertimecomparedwith microfractureandmosaicplasty.Similarly,ofthefivestudiesthatreportedTegnerscores,fourstudies reportednosignificantdifferenceintheeffectivenessofMACI/ACIovertimecomparedwithcomparator procedures;however,onestudyreportedthatMACIwasmoreeffectiveovertimecomparedwith microfracture.

Moststudiesthatassessedtheseoutcomesreportedthatqualityoflifeandpainscoreswerenotsignificantly differentfollowingMACI/ACIcomparedwithcomparatorprocedures;however,onestudydidreportthat the improvementinpainscoresfollowingACIwassignificantlybettercomparedwithdebridement.

Imagingoutcomes,reportedinalimitednumberofstudies,revealednosignificantdifferenceinthequality

ofarticularcartilagerepairfollowingMACI/ACIcomparedwithcomparatorprocedures.Similarly,one studyreportedthatatfiveyearfollow-up,therewasnosignificantdifferenceinthefrequencyof radiographicchangesthatwereindicativeofosteoarthritisinMACI/ACIpatientscomparedwithpatients whounderwentmicrofracture.

Overall,intheshorttomediumterm,theeffectivenessofMACI/ACIappearstobecomparabletothose comparatorproceduresevaluatedinthisassessment.

Cost-effectiveness

Afulleconomicevaluationwasnotundertakenbecauseofthelackofevidencesupportingthesuperior effectivenessofMACI/ACI.TheresultsofthecostinganalysisdemonstratedthatMACI/ACIismorecostly thaneithermicrofractureormosaicplasty.Thereasonfortheadditionalcostistwo-fold.Firstly,MACI/ACI requiretwoseparatesurgicalprocedures,thefirsttobiopsythechondrocytecellsandthesecondtoimplant theculturedcells.Mosaicplastyandmicrofractureonlyrequireasingleprocedure.Thereforetheextra procedurehasflow-oncostsintermsofadditionalMBSitemsandpatientco-payments.Secondly, MACI/ACIrequirestheisolationandgrowthofchondrocytecellsintissueculture.Thiscostissignificant andaddsanextra$11,400perkneerepaired.

PreciseidentificationofthenumberofpatientseligibleforMACI/ACIwasdifficult,andtwoestimateswere calculated.Thefirstestimatewasbasedonthenumberofpatientscurrentlyundergoinghyalinecartilage repair.Thesecondestimatewasbasedonthepotentialnumberofpatientssuitableforcartilagerepair,this beinganestimateoftheunmetdemandforMACI/ACI.Thefinancialimplicationswereindicativeonly, sincetheyassumeda100percentswitchfrommosaicplastyormicrofracturetoMACI/ACI.Theactual uptakerateofMACI/ACIwasnotestimatedbecauseoftheuncertaintyaroundthisvalue.

Patientcharacteristicsanddamagepathologywerenotconsidered.AssuggestedbytheAdvisoryPanel,the sizeandnumberoflesionsmayinfluencethepreferredtreatmentoptions.Alsonotconsideredwasthe possibilityofusingMACI/ACIasasecondlinetreatmentinpatientswhohadpreviouslyfailedeither microfractureormosaicplasty.

Methods

TheevidenceregardingtheuseofMACIandACIforthetreatmentofarticularcartilagedefectswas systematicallyassessed.PubMed,EMBASEandtheCochraneLibraryweresearchedforrelevantliterature frominceptionofthedatabasestoMarch2010.Studieswereincludedinthereviewusingpre-determined PICOselectioncriteriaandreasonsforexclusionweredocumented.Thequalityofstudieswasassessed,data wereextractedinastandardisedmanner,andresultswerereportednarratively.