© 2018 Journal of Natural Science, Biology and Medicine | Published by Wolters Kluwer - Medknow180

Original Article

IntroductIon

Painisthemostcommoncomplaintinosteoarthritis(OA),whichrestrictsthephysicalactivityofthepatientsaswellasdecreasesworkperformance.[1]InOAoftheknee,painmayarisefromperiostealelevation,trabecularmicrofractures,capsulardistension,and/orsynovialinflammation.Factorscomplicating determination of the source of painmayincludevarusorvagusdeformity,weight issues, and theemotionalimpactofchronicpain.Oncethecauseofpainis identified, treatment plan can be formulated.[2] Painis themost common reason in patientswithOA to seekmedicalhelp.[3]ThecurrenttreatmentstrategiesforOAaimtoeducate thepatientaboutOA,alleviatepain,optimizeandmaintain joint function and prevent or suppress theprogressionofadversestructuralchangeaffectingthejointtissues.[4]

Commonlyusedpharmacologicalagentsforpainmanagementare nonsteroidal anti‑inflammatory drugs (NSAIDs).[5]Most of the patientswithOA takemedication for a longperiodandhaveanumberofcomorbidities,whichrequiresconcomitantmedication,increasingthelikelihoodofadverseevents includinggastrointestinal (GI) injury.[6]There is anincreasingdemandformoreeffectiveandsafertreatmentforOA.PiroxicamisanNSAID,anoxicamderivative,whichareenolicacidsthatinhibitcyclooxygenase(COX)enzymenon

A Comparative Study of Efficacy and Safety of Piroxicam and Naproxen in the Management of Pain in Osteoarthritis of the

KneeYaseen Mohammed, Sarala Narayana, H. S. Arun1

Departments of Pharmacology and 1Orthopaedics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India

Introduction: Osteoarthritis(OA)isadegenerativejointdiseaseandcauseforfunctionaldisability.OAischaracterizedbytheinsidiousonsetofpainandlimitedrangeofmovements.PiroxicamandnaproxenareusedinOA,rheumatoidarthritis,acutegoutyarthritis,migraine,dysmenorrhea,andpostoperativepain.TheaimofthisstudywastocomparetheefficacyandsafetyofthesedrugsinpatientswithOAoftheknee.Materials and Methods:Thiswasarandomized,open‑label,comparative,parallelgroupstudyconductedinpatientswithOAofkneejoints.Theyreceivedeitheroralpiroxicam20mgornaproxen500mgtwicedailyfor6weeks.ThepainwasassessedusingVisualAnalogScale(VAS)andWesternOntarioandMcMasterUniversitiesArthritisIndex(WOMAC)scoresatbaseline,2nd,4th,and6thweek.Patientsatisfactionscore(PSS)andqualityoflifewereassessedatfollow‑up.AdverseeffectswereassessedusingtheWorldHealthOrganizationcausalityscale.Descriptiveandinferentialstatisticswereused. Results:Atotalof110patientswererecruited,47malesand63females,100completedthestudy(51inGroupPand49inGroupN).BothpiroxicamandnaproxensignificantlyreducedVASandWOMACscoresatthe2nd,4th,and6thweek(P=0.001)comparedtobaseline,butthiswasnotsignificantbetweenthegroups.PSSwassignificantly(P=0.03)highat4thand6thweekwhencomparedtoweek2withbothmedications,butbetweenthemedications,itwasinsignificant(P=0.10).Theadverseeffects suchasepigastricdiscomfort,nausea,andvomitingwereobservedwithboth thedrugs,but itwasmorewithnaproxen.Conclusion:Piroxicamwasaseffectiveasnaproxeninrelievingpainandimprovingtherangeofmovementswithlessadverseeffects.

Keywords:Kneejoints,naproxen,osteoarthritis,piroxicam

Address for correspondence: Dr. Sarala Narayana, Departments of Pharmacology, Sri Devaraj Urs Medical College,

Sri Devaraj Urs Academy of Higher Education and Research, Tamaka, Kolar, Karnataka, India.

E‑mail: n_sarala@rediffmail.com

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Quick Response Code:Website:www.jnsbm.org

DOI:10.4103/jnsbm.JNSBM_154_17

Abstract

How to cite this article: MohammedY, Narayana S,Arun HS.Acomparativestudyofefficacyandsafetyofpiroxicamandnaproxeninthemanagementofpaininosteoarthritisoftheknee.JNatScBiolMed2018;9:180‑4.

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Mohammed, et al.: Mohammed et al Piroxicam and naproxen in osteoarthritis

Journal of Natural Science, Biology and Medicine ¦ Volume 9 ¦ Issue 2 ¦ July-December 2018 181

selectively.Itresultsininhibitionofprostaglandinproduction,whichisthemainmediatorofpain.Ithasalonghalf‑life(t½)ofapproximately50handavailableasoralformulation,andhence, it is suitable for use inOA.[5] It is also used in themanagementofpostoperativepain,musculoskeletaldisorders,anddysmenorrhea.[7]IthasshownclinicalefficacyinrelievingpainassociatedwithOAandrheumatoidarthritis,especiallywhere there is an associated inflammatory component.[8] Italso suppresses primary and secondary lesions of adjuvantarthritis.[9]NaproxenisanNSAID,apropionicacidderivativeandisanonselectiveCOXenzymeinhibitor.Itiswell‑absorbedorallyandhasat½of14h.[5]Ithasclinicallyprovenefficacywithregardtoanalgesiaandreliefofmorningstiffness.[10]Ithassideeffectssuchasabdominalpain,gastritis,drowsiness,nausea,vomiting,dizziness,andpruritis.

mAterIAls And methods

A randomized, open‑label, comparative, parallel group,prospectivestudywasconductedinpatientsdiagnosedwithOAofkneejoints.ThisstudywascarriedoutbytheDepartmentsofPharmacologyandOrthopaedicsinR.LJalappaHospitalandResearchCentreattachedtoSriDevarajUrsMedicalCollege,Tamaka,Kolar,fromJanuary2015toJune2016.Patientsofeithergender,agedbetween40and70yearswithsymptomaticidiopathicOAofbilateralkneejointinvolvementforaminimumperiodof6months,radiologicalevidenceofOAofkneejointsandmorning stiffnessof<30mindurationwith crepitusonmotionwere included in the study.Exclusioncriteriawere:patientswithahistoryofsurgeryoracutetraumatothekneejointwithin6months,historyofpepticulcer,GIbleeding,psychiatricillness and bronchial asthma, acute inflammatory arthritis,pseudogout, or severe osteoporosis, thosewith derangedhepaticorrenalparametersandalsowhowerehypersensitivetopiroxicamornaproxen.PatientswithpainduetoOAofkneejointswererecruited,randomizedbysimplerandomizationina1:1ratiointotwogroupsof55each,withGroupPreceivingpiroxicam20mgandGroupNreceivingnaproxen500mg,bothmedicationsgivenorallytwicedailyfor6weeks.Patientswerefollowedupat2nd,4th,and6thweek.Thepatientsrecruitedinbothgroupswerematchedintermsofage,gender,weight,andbodymassindex(BMI).Theywereinstructedtoperformthemildexercise(kneeflexionandhamstringstretch),applyhotfomentation,anduseIndianstyletoilet.

Demographicdetailsandrelevanthistorywerecollectedfromthepatientat the timeof recruitment.Clinicalexaminationincluding general physical examination and knee jointsexamination(inspection,palpation,therangeofmovementsandmeasurements) was performed. Routine laboratoryinvestigations such as complete hemogram, randombloodsugar,bloodurea,serumcreatinine, liver function test,andurine routinewere carried out at baseline.X‑rays of kneejointsweretakenatbaselinefordiagnosis.Rheumatoidfactorwasdonewhenrequired.TheVisualAnalogScale(VAS)[6]andWesternOntario andMcMasterUniversitiesArthritisIndex (WOMAC)[1] scoreswere assessed at baseline and

at each follow‑up.TheVAS scorewas graded from 0 to10accordingtopatient’sresponse.WOMACisasubjectivescoreconsistingofsubscalesintermsofpain,stiffness,andphysicalfunction.Alltheparametersweregradedonascaleof0–4dependingontheseverity,fromnonetosevere.ThereductioninWOMACscoreindirectlyindicatesimprovementin thequalityof life(QOL).If theVASscorewas>3afterinitiatingthetreatmentwithstudydrugs,oraltramadol50mgwas used as rescue analgesic. Patients’ satisfactionwithrespecttopainreliefwasassessedusingpatient’ssatisfactionscore(PSS)ateachfollow‑up.PSSwasgradedas1=poor,2=fair,3=good,and4=excellent.Duringthefollow‑up,thesafetyofthedrugswasmonitoredusingtheWorldHealthOrganizationcausalityscale.

Statistical methodsTodetectameandifferenceofVASscoreof0.98attheendof1monthwithaneffectsizeof0.564,powerof80%,alphaerrorof5%,anddropoutrateof10%,therequiredsamplesizewas55patientspergroup.Thedemographicdatawereanalyzedusingdescriptivestatistics.TheVASandWOMACscoreswereassessedusingrepeatedmeasureanalysisofvariancefollowedbyBonferroniposthoc testwithin thegroup andunpairedt‑testbetweenthegroups.AdverseeventswereanalyzedusingChi‑squaretest.Patient’ssatisfactionscorewasanalyzedusingWilcoxonandMann–WhitneyU‑test.QOLwasanalyzedusingdescriptivestatistics.Thevalueof P <0.05wasconsideredasstatisticallysignificant.

results

PatientswithOAofboththekneejointsrecruitedwere110but100patientscompletedthe6weeksstudyperiod[Figure1].Theanalysiswasperformedforpatientswhohavecompletedthestudy.Thedemographicparameterssuchasage,gender‑wisedistribution,BMI,andoccupationwerecomparableinboththegroups.Among110patients, themajorityofpatientsinbothgroupswerefemales(57.3%).Housewivesconstitutedfor>40%inboththegroups[Table1].

TheVASscorewithinthegroupsandbetweenbothmedicationsisrepresentedinTable2.

ThereductioninmeanVASscorewasstatisticallysignificantateachfollow‑upcomparedtobaselineinbothgroups(P=0.001).Byweek6,therewassignificant(P=0.001)decreaseinVASscorewithboththemedications.ThereductioninmeanVASscorewasnotsignificant(P=0.20, P =0.81, P =0.38)betweenthetreatmentsatanypointoftime[Table2].Theareaunderthecurveforareductioninpaininpatientsreceivingmedicationsin both the groups [Figure 2]was calculated by trapezoidmethod.Thedecreaseintheareaoftrapezoidoveraperiodindicatesthereducedintensityofpainwithbothmedications.Whenthisareawascomparedbetweenmedications,itwaslesswithpiroxicam(5.33)comparedtonaproxen(5.45)atweek6.

TheWOMAC scorewithin the groups and between bothmedicationsisrepresentedinTable3.Thereductioninpain,

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stiffness, and physical function scoreswere statisticallysignificant (P = 0.001) atweeks 2, 4, and 6 compared tobaselinewith both themedications [Table 3]. Based onthe physical function subscale ofWOMAC, reduction inscoreindicatesgradualimprovementintheQOLat2nd,4th,and6thweek.When the scoresof subcaleswere comparedbetween groups, the reductionwas insignificant at eachfollow‑up.ThereductioninWOMACscorewasstatisticallysignificant (P = 0.001) atweeks 2, 4, and 6 compared to

baselinewithboththemedications.Morethan75%decreaseinthescorewasobservedatweek6.ThereductioninmeanWOMAC scorewas insignificant between piroxicam andnaproxenatallthefollow‑upvisits.

Inpiroxicamgroup,64.7%ofpatientsgradedtheirsatisfactionas good at both 4th and 6thweek.Nearly 5.9%of patientsexpressed their satisfaction as excellent atweek 6.ThisincreaseinPSSatbothweekswasstatisticallysignificantascomparedtoweek2(P=0.03).At4thweek,60.7%ofpatientsgradedtheirsatisfactionasgood,whereas63.2%at6thweekingroupN.PSSwassignificantlyimprovedat4thand6thweekcompared toweek 2with naproxen (P = 0.03). PSSwasinsignificantbetweenthemedications(P=0.10)[Figure3].Adverseeffectswithpiroxicamandnaproxenwereepigastricdiscomfort(19.2%vs.32%),nausea(15.3%vs.18.8%),andvomiting(15.3%vs.24.5%).Thesesymptomsweretreatedwithomeprazole20mgoncedailytilltheysubsided.

dIscussIon

OA is one of the most common degenerative diseaseparticularlyaffectingthekneejoints,anditisthemajorcause

Table 1: Comparison of demographic parameters between Group P and Group N

Variables Group P (n=55) Group N (n=55)Age(years),mean±SD 55.24±9.80 52.03±9.00Male/female 23/32 24/31BMI(kg/m2),mean±SD 25.80±4.32 26.00±4.57Housewife 24 22Farmer 16 18Teacher 8 9Tailor 7 6BMI:Bodymassindex,SD:Standarddeviation

Figure 1: Consort flow chart representing recruitment, randomization and follow‑up

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of disability in elderly.OA is a disease of synovial jointscharacterizedbyinflammationofthejointcapsule,cartilagelossalongwithperiarticularbonedamage.Itisassociatedwithpain,impairedmuscularstability,reducedrangeofmovement,andfunctionaldisability.OArarelyoccursbeforetheageof

40yearsbutby75yearsatleast85%ofthepopulationhaveeitherclinicalorradiographicevidenceofthedisease.OAisanappropriatemodeltoassesstheefficacyofnewanalgesicsatrepeateddoses.[5]NSAIDsarewidelyusedforthetreatmentof pain in patientswithOA.However, they are associatedwithadverseeffectsmainlyGI,suchasepigastricdiscomfort,dyspepsia,abdominalpain,nausea,andvomiting.Thus,thedecisiontoprescribeNSAIDsisbasedontheireffectivenesstoreducepainwithlessadverseeffects.

In thepresent study,110patientsdiagnosedwithmoderateto severeOA of both the knee jointswere recruited andrandomizedasshowninFigure1.Theyreceivedpiroxicam20mginGroupPornaproxen500mgingroupNtwicedailyfor6weeks.Onehundredpatientscompletedthestudyperiod.Mostofthepatients(70%)wereinthefifthdecadeoflifewhichsubstantiatesthatOAoccurrenceincreasesasageadvances.Someof thefactorscontributing toOAinelderlycouldbedegenerativechangesinthemenisci,jointligaments,increasedboneturnoveraswellascalcificationofjointtissues.[11]

Thefemalepatientsweremoreinboththegroups.AstudybyRugstadetal.,comparingpiroxicam20mgwithnaproxen750mgoncedailyinOAofthekneealsohadmorefemalepatients.[12]Thiscouldbebecauseinwomen,tendonsaremoreelasticandkneejointsarenotalignedstraightasinmenwhichleadtoinjuriesandmaymanifestasOAinthelaterpartoftheirlife.Inaddition,femalepatientswhosemothershadOAmightdevelopthisdiseaseinthesamejointandatthesameage.Estrogenprotectscartilagefrominflammation,butduringandaftermenopause,thedecreasedestrogenlevelleadstohighriskofOA.[13]Obesitycontributes toextra stressonknees,whichleadstocartilagebreakdown,andinthisstudy,mostpatientswereoverweight.

WeobservedthatbothpiroxicamandnaproxensignificantlyreducedtheVASscoresat2nd,4th,and6thweekcomparedtobaseline[Table2].Thereduction inpainwassignificant inpatientsreceivingeithermedication,andalsotherewasagoodclinicalresponse.Betweenthegroups,reductioninVASscorewasnotstatisticallysignificantatanyofthefollow‑upvisits.InastudybyRichyetal.,piroxicamwassimilarinefficacycomparedtootherNSAIDsinreducingpaininpatientswithOAoftheknee.[14]Allegrinietal.havereportedthatpiroxicam

Table 3: Comparison of subscales of Western Ontario and McMaster Universities Arthritis Index within and between the groups at all evaluation points

Mean±SD P (between groups)Group P Group N

PainsubscaleBaseline 13.25±2.25 13.27±1.95 0.422ndweek 09.92±1.74* 09.81±1.62* 0.364thweek 07.03±1.34* 07.00±1.41* 0.286thweek 04.35±0.82* 04.41±0.86* 0.17

StiffnesssubscaleBaseline 04.73±0.50 04.58±0.53 0.262ndweek 03.51±0.50* 03.55±0.54* 0.414thweek 02.51±0.50* 02.55±0.54* 0.746thweek 02.00±0.00* 02.02±0.14* 0.32

PhysicalfunctionsubscaleBaseline 39.63±3.34 39.56±2.92 0.542ndweek 29.66±3.57* 30.40±2.85* 0.404thweek 19.47±3.08* 20.07±3.25* 0.126thweek 09.52±2.28* 09.89±1.99* 0.20

*P=0.001whencomparingtheevaluationpointswithbaseline.SD:Standarddeviation

Table 2: Comparison of mean visual analog scale scores within and between the groups at all evaluation points

Mean±SD P (between groups)

Group P Group NBaseline 8.00±1.51 7.78±1.45 0.402ndweek 5.52±1.35* 5.45±1.32* 0.204thweek 3.53±1.10* 3.55±1.12* 0.816thweek 1.80±0.70* 1.90±0.60* 0.38*P=0.001whencomparingtheevaluationpointswithbaseline.SD:Standarddeviation

Figure 3: Patient’s satisfaction scoreFigure 2: Area under curve – piroxicam and naproxen

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patchwaseffectivecomparedtoplaceboinreducingpainduetoOAofthelumbarvertebra.[15]Alhoetal.studyshowedthatpiroxicamandnaproxenweresimilarinefficacywhenusedforOAofthehipjoint.[16]Inthisstudy,theintensityofpainexperiencedbythepatientsover6weeksisrepresentedbytheareaunderthecurveandthosereceivingpiroxicam(5.33)hadmarginallybetterpainreliefcomparedtonaproxen(5.45)atweek6asshowninFigure2.

The parameters ofWOMACdepicting pain, stiffness, andphysicalfunctionweresignificantlyreducedinbothgroupsateachfollow‑upcomparedtobaseline[Table3].Inthisstudy,boththedrugssignificantlyreducedWOMACscoreat2nd,4th,and6thweekcomparedtobaseline.ReductioninWOMACscoreimpliesareductioninpain,improvementinflexibilityofjoints,andrangeofmovements.Thishelpsthepatientincarryingoutday‑to‑dayactivitiesindependently,thusreductioninthisscoreindicatesimprovementintheQOLofthepatients.TherewasnosignificantreductioninWOMACscoresbetweenthegroupsduringthefollow‑upperiod.InastudybySmithetal., itwasobserved thatNSAIDssuchaspiroxicamandnaproxenreducedpainsimilartoopioidsinpatientswithOAoftheknee.[17]ReductioninVASandWOMACscorestothesameextentbyboththedrugsinourstudyimpliesthattheyareequallyefficaciousinreducingthesymptomsandsignsofOA.

Wealso assessed thePSSat 2nd, 4th, and6thweek. Inboththegroups,morenumberofpatients expressed satisfactionas “Good” with the study medications. There was animprovementinPSSinboththegroupsfrom2ndweekto4thand6thweek[Figure3].Therewasnosignificantdifferenceinthesatisfactionscorebetweenpiroxicamandnaproxen(P=0.10).This shows thatpatients inboth thegroupshadpain reliefandwere able to perform their regular activitieswith lessdependence.Most of our patientswere in thefifth decadeof life duringwhich they have to depend on their familymembersforsupport,sincetheycouldcarryouttheiractivitiesindependently,theirsatisfactionscoresimproved.

In this study, bothmedicationswerewell‑tolerated, andadverse effectsweremild in nature.The adverse effectssuch as epigastric discomfort, nausea, and vomiting,wereobservedwithboththedrugs,butthenumberwasmorewithnaproxen than piroxicam, and thesemanifestationsweretreatedsymptomatically. In thestudydonebyRichyetal.,patientswithOAof knee observed that piroxicam causedlesser adverse effects compared to otherNSAIDs exceptmeloxicam.TheadverseeffectswerelessevenwithtwicedailyadministrationofpiroxicamcomparedtooncedailyintakeofotherNSAIDs.[14]

conclusIon

The pain relief and patient satisfactionwere similarwithboththedrugsbutanumberofadverseeffectswerelesswithpiroxicam,suggestingittobeabetteralternativetonaproxeninpatientswithOAofkneejoints.

Financial support and sponsorshipNil.

Conflicts of interestTherearenoconflictsofinterest.

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