Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis

250 Pages·2016·1.69 MB·English

CochraneDatabaseofSystematicReviews
Non-steroidal anti-inflammatory drugs (NSAIDs) for axial
spondyloarthritis (ankylosing spondylitis and non-
radiographic axial spondyloarthritis) (Review)
KroonFPB,vanderBurgLRA,RamiroS,LandewéRBM,BuchbinderR,FalzonL,vanderHeijdeD
KroonFPB,vanderBurgLRA,RamiroS,LandewéRBM,BuchbinderR,FalzonL,vanderHeijdeD.
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis (ankylosing spondylitis andnon-radiographicaxialspondy-
loarthritis).
CochraneDatabaseofSystematicReviews2015,Issue7.Art.No.:CD010952.
DOI:10.1002/14651858.CD010952.pub2.
www.cochranelibrary.com
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARYOFFINDINGSFORTHEMAINCOMPARISON . . . . . . . . . . . . . . . . . . . 4
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Figure5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
ADDITIONALSUMMARYOFFINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 27
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Analysis1.1.Comparison1TraditionalNSAIDvsPlacebo,Outcome1PainonVAS. . . . . . . . . . . . 143
Analysis1.2.Comparison1TraditionalNSAIDvsPlacebo,Outcome2Withdrawalsduetoadverseevents. . . . 144
Analysis1.3.Comparison1TraditionalNSAIDvsPlacebo,Outcome3BASDAI. . . . . . . . . . . . . 145
Analysis1.4.Comparison1TraditionalNSAIDvsPlacebo,Outcome4Patient’sglobalassessmentofdiseaseactivity. 145
Analysis1.5.Comparison1TraditionalNSAIDvsPlacebo,Outcome5Durationofmorningstiffness. . . . . . 146
Analysis1.6.Comparison1TraditionalNSAIDvsPlacebo,Outcome6CRP. . . . . . . . . . . . . . . 147
Analysis1.7.Comparison1TraditionalNSAIDvsPlacebo,Outcome7ASAS20. . . . . . . . . . . . . 148
Analysis1.8.Comparison1TraditionalNSAIDvsPlacebo,Outcome8ASASpartialremission. . . . . . . . 148
Analysis1.9.Comparison1TraditionalNSAIDvsPlacebo,Outcome9BASFI. . . . . . . . . . . . . . 149
Analysis1.10.Comparison1TraditionalNSAIDvsPlacebo,Outcome10Chestexpansion. . . . . . . . . . 149
Analysis1.11.Comparison1TraditionalNSAIDvsPlacebo,Outcome11Schober’stest. . . . . . . . . . . 150
Analysis1.12.Comparison1TraditionalNSAIDvsPlacebo,Outcome12Painrelief≥50%. . . . . . . . . 151
Analysis1.13.Comparison1TraditionalNSAIDvsPlacebo,Outcome13Numberofanyadverseevents. . . . . 152
Analysis1.14.Comparison1TraditionalNSAIDvsPlacebo,Outcome14Numberofseriousadverseevents. . . . 153
Analysis1.15.Comparison1TraditionalNSAIDvsPlacebo,Outcome15Numberofadverseeventsperorgansystem. 154
Analysis2.1.Comparison2COX-2vsPlacebo,Outcome1PainonVAS. . . . . . . . . . . . . . . . 156
Analysis2.2.Comparison2COX-2vsPlacebo,Outcome2Withdrawalsduetoadverseevents. . . . . . . . . 156
Analysis2.3.Comparison2COX-2vsPlacebo,Outcome3BASDAI. . . . . . . . . . . . . . . . . 157
Analysis2.4.Comparison2COX-2vsPlacebo,Outcome4Patient’sglobalassessmentofdiseaseactivity. . . . . 158
Analysis2.5.Comparison2COX-2vsPlacebo,Outcome5Durationofmorningstiffness. . . . . . . . . . 159
Analysis2.6.Comparison2COX-2vsPlacebo,Outcome6CRP. . . . . . . . . . . . . . . . . . . 159
Analysis2.7.Comparison2COX-2vsPlacebo,Outcome7ASAS20. . . . . . . . . . . . . . . . . 160
Analysis2.8.Comparison2COX-2vsPlacebo,Outcome8ASASpartialremission. . . . . . . . . . . . . 160
Analysis2.9.Comparison2COX-2vsPlacebo,Outcome9BASFI. . . . . . . . . . . . . . . . . . 161
Analysis2.10.Comparison2COX-2vsPlacebo,Outcome10Chestexpansion. . . . . . . . . . . . . . 161
Analysis2.11.Comparison2COX-2vsPlacebo,Outcome11Schober’stest. . . . . . . . . . . . . . . 162
Analysis2.12.Comparison2COX-2vsPlacebo,Outcome12Painrelief≥50%. . . . . . . . . . . . . 162
Analysis2.13.Comparison2COX-2vsPlacebo,Outcome13Numberofanyadverseevents. . . . . . . . . 163
Analysis2.14.Comparison2COX-2vsPlacebo,Outcome14Numberofseriousadverseevents. . . . . . . . 164
Analysis2.15.Comparison2COX-2vsPlacebo,Outcome15Numberofadverseeventsperorgansystem. . . . . 165
Analysis3.1.Comparison3COX-2vstraditionalNSAID,Outcome1PainonVAS. . . . . . . . . . . . 166
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial i
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Analysis3.2.Comparison3COX-2vstraditionalNSAID,Outcome2Withdrawalsduetoadverseevents. . . . . 167
Analysis3.3.Comparison3COX-2vstraditionalNSAID,Outcome3BASDAI. . . . . . . . . . . . . . 168
Analysis3.4.Comparison3COX-2vstraditionalNSAID,Outcome4Patient’sglobalassessmentofdiseaseactivity. 168
Analysis3.5.Comparison3COX-2vstraditionalNSAID,Outcome5Durationofmorningstiffness. . . . . . 169
Analysis3.6.Comparison3COX-2vstraditionalNSAID,Outcome6CRP. . . . . . . . . . . . . . . 170
Analysis3.7.Comparison3COX-2vstraditionalNSAID,Outcome7ASAS20. . . . . . . . . . . . . . 170
Analysis3.8.Comparison3COX-2vstraditionalNSAID,Outcome8ASASpartialremission. . . . . . . . . 171
Analysis3.9.Comparison3COX-2vstraditionalNSAID,Outcome9BASFI. . . . . . . . . . . . . . 172
Analysis3.10.Comparison3COX-2vstraditionalNSAID,Outcome10BASMI. . . . . . . . . . . . . 172
Analysis3.11.Comparison3COX-2vstraditionalNSAID,Outcome11Chestexpansion. . . . . . . . . . 173
Analysis3.12.Comparison3COX-2vstraditionalNSAID,Outcome12Schober’stest. . . . . . . . . . . 173
Analysis3.13.Comparison3COX-2vstraditionalNSAID,Outcome13Painrelief≥50%. . . . . . . . . 174
Analysis3.14.Comparison3COX-2vstraditionalNSAID,Outcome14Numberofanyadverseevents. . . . . 174
Analysis3.15.Comparison3COX-2vstraditionalNSAID,Outcome15Numberofseriousadverseevents. . . . 175
Analysis3.16.Comparison3COX-2vstraditionalNSAID,Outcome16Numberofadverseeventsperorgansystem. 176
Analysis4.1.Comparison4NSAIDvsNSAID,Outcome1PainonLikertscale. . . . . . . . . . . . . . 179
Analysis4.2.Comparison4NSAIDvsNSAID,Outcome2PainonVAS. . . . . . . . . . . . . . . . 180
Analysis4.3.Comparison4NSAIDvsNSAID,Outcome3Withdrawalsduetoadverseevents. . . . . . . . 181
Analysis4.4.Comparison4NSAIDvsNSAID,Outcome4Patient’sglobalassessmentofdiseaseactivity. . . . . 183
Analysis4.5.Comparison4NSAIDvsNSAID,Outcome5Durationofmorningstiffness. . . . . . . . . . 183
Analysis4.6.Comparison4NSAIDvsNSAID,Outcome6Severityofmorningstiffness. . . . . . . . . . . 184
Analysis4.7.Comparison4NSAIDvsNSAID,Outcome7CRP. . . . . . . . . . . . . . . . . . . 185
Analysis4.8.Comparison4NSAIDvsNSAID,Outcome8ESR. . . . . . . . . . . . . . . . . . . 185
Analysis4.9.Comparison4NSAIDvsNSAID,Outcome9Lateralspinalflexion. . . . . . . . . . . . . 186
Analysis4.10.Comparison4NSAIDvsNSAID,Outcome10Chestexpansion. . . . . . . . . . . . . . 186
Analysis4.11.Comparison4NSAIDvsNSAID,Outcome11Tragus-to-walldistance. . . . . . . . . . . 187
Analysis4.12.Comparison4NSAIDvsNSAID,Outcome12Occiput-to-walldistance. . . . . . . . . . . 188
Analysis4.13.Comparison4NSAIDvsNSAID,Outcome13Schober’stest. . . . . . . . . . . . . . . 188
Analysis4.14.Comparison4NSAIDvsNSAID,Outcome14Painrelief≥50%. . . . . . . . . . . . . 189
Analysis4.15.Comparison4NSAIDvsNSAID,Outcome15Numberofanyadverseevents. . . . . . . . . 190
Analysis4.16.Comparison4NSAIDvsNSAID,Outcome16Numberofseriousadverseevents. . . . . . . . 192
Analysis4.17.Comparison4NSAIDvsNSAID,Outcome17Adverseeventsperorgansystem. . . . . . . . 192
Analysis5.1.Comparison5NaproxenvsotherNSAID,Outcome1PainonVAS. . . . . . . . . . . . . 196
Analysis5.2.Comparison5NaproxenvsotherNSAID,Outcome2Withdrawalsduetoadverseevents. . . . . . 197
Analysis5.3.Comparison5NaproxenvsotherNSAID,Outcome3BASDAI. . . . . . . . . . . . . . . 197
Analysis5.4.Comparison5NaproxenvsotherNSAID,Outcome4Patient’sglobalassessmentofdiseaseactivity. . 198
Analysis5.5.Comparison5NaproxenvsotherNSAID,Outcome5Durationofmorningstiffness. . . . . . . 198
Analysis5.6.Comparison5NaproxenvsotherNSAID,Outcome6ASAS20. . . . . . . . . . . . . . . 199
Analysis5.7.Comparison5NaproxenvsotherNSAID,Outcome7ASASpartialremission. . . . . . . . . . 199
Analysis5.8.Comparison5NaproxenvsotherNSAID,Outcome8BASFI. . . . . . . . . . . . . . . 200
Analysis5.9.Comparison5NaproxenvsotherNSAID,Outcome9Schober’stest. . . . . . . . . . . . . 200
Analysis5.10.Comparison5NaproxenvsotherNSAID,Outcome10Numberofanyadverseevents. . . . . . 201
Analysis5.11.Comparison5NaproxenvsotherNSAID,Outcome11Numberofseriousadverseevents. . . . . 202
Analysis5.12.Comparison5NaproxenvsotherNSAID,Outcome12Numberofadverseeventsperorgansystem. . 203
Analysis6.1.Comparison6LowdosevshighdoseNSAID,Outcome1PainonVAS. . . . . . . . . . . . 205
Analysis6.2.Comparison6LowdosevshighdoseNSAID,Outcome2Withdrawalsduetoadverseevents. . . . 206
Analysis6.3.Comparison6LowdosevshighdoseNSAID,Outcome3BASDAI. . . . . . . . . . . . . 207
Analysis6.4.Comparison6LowdosevshighdoseNSAID,Outcome4Patient’sglobalassessmentofdiseaseactivity. 207
Analysis6.5.Comparison6LowdosevshighdoseNSAID,Outcome5Durationofmorningstiffness. . . . . . 208
Analysis6.6.Comparison6LowdosevshighdoseNSAID,Outcome6CRP. . . . . . . . . . . . . . . 209
Analysis6.7.Comparison6LowdosevshighdoseNSAID,Outcome7ASAS20. . . . . . . . . . . . . 209
Analysis6.8.Comparison6LowdosevshighdoseNSAID,Outcome8ASASpartialremission. . . . . . . . 210
Analysis6.9.Comparison6LowdosevshighdoseNSAID,Outcome9BASFI. . . . . . . . . . . . . . 211
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial ii
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Analysis6.10.Comparison6LowdosevshighdoseNSAID,Outcome10BASMI. . . . . . . . . . . . . 211
Analysis6.11.Comparison6LowdosevshighdoseNSAID,Outcome11Chestexpansion. . . . . . . . . . 212
Analysis6.12.Comparison6LowdosevshighdoseNSAID,Outcome12Schober’stest. . . . . . . . . . . 212
Analysis6.13.Comparison6LowdosevshighdoseNSAID,Outcome13Painrelief≥50%. . . . . . . . . 213
Analysis6.14.Comparison6LowdosevshighdoseNSAID,Outcome14Numberofanyadverseevents. . . . . 214
Analysis6.15.Comparison6LowdosevshighdoseNSAID,Outcome15Numberofseriousadverseevents. . . . 215
Analysis6.16.Comparison6LowdosevshighdoseNSAID,Outcome16Numberofadverseeventsperorgansystem. 216
Analysis7.1.Comparison7Subgroupanalysis:traditionalandCOX-2NSAIDvsPlacebo,Outcome1Pain(VAS). . 218
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 246
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial iii
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Non-steroidal anti-inflammatory drugs (NSAIDs) for axial
spondyloarthritis (ankylosing spondylitis and non-radiographic
axial spondyloarthritis)
FélinePBKroon1,LennartRAvanderBurg1,SofiaRamiro2,RobertBMLandewé2,3,RachelleBuchbinder4,LouiseFalzon5,Désirée
vanderHeijde1
1DepartmentofRheumatology,LeidenUniversityMedicalCenter,Leiden,Netherlands.2DepartmentofClinicalImmunologyand
Rheumatology,AcademicMedicalCenter,UniversityofAmsterdam,Amsterdam,Netherlands.3DepartmentofRheumatology,Atrium
MedicalCentre,Herleen,Netherlands.4MonashDepartmentofClinicalEpidemiology,CabriniHospital,DepartmentofEpidemiology
and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Australia. 5Center for
BehavioralCardiovascularHealth,ColumbiaUniversityMedicalCenter,NewYork,NY,USA
Contact address: Féline PB Kroon, Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
[email protected].
Editorialgroup:CochraneMusculoskeletalGroup.
Publicationstatusanddate:New,publishedinIssue7,2015.
Reviewcontentassessedasup-to-date: 18June2014.
Citation: Kroon FPB, van der Burg LRA, Ramiro S, Landewé RBM, Buchbinder R, Falzon L, van der Heijde D. Non-steroidal
anti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxialspondyloarthritis).
CochraneDatabaseofSystematicReviews2015,Issue7.Art.No.:CD010952.DOI:10.1002/14651858.CD010952.pub2.
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Axialspondyloarthritis(axSpA)comprisesankylosingspondylitis(radiographicaxSpA)andnon-radiographic(nr-)axSpAandisasso-
ciatedwithpsoriasis,uveitisandinflammatoryboweldisease.Non-steroidalanti-inflammatorydrugs(NSAIDs)arerecommendedas
first-linedrugtreatment.
Objectives
TodeterminethebenefitsandharmsofNSAIDsinaxSpA.
Searchmethods
WesearchedCENTRAL,MEDLINEandEMBASEto18June2014.
Selectioncriteria
Randomisedcontrolledtrials(RCTs)orquasi-RCTsofNSAIDsversusplacebooranycomparatorinadultswithaxSpAandobservational
cohortstudies studying thelong termeffect(≥ sixmonths) of NSAIDs on radiographic progression or adverse events(AEs).The
maincomparionsweretraditionalorCOX-2NSAIDsversusplacebo.Themajoroutcomeswerepain,BathAnkylosingSpondylitis
DiseaseActivity Index(BASDAI),BathAnkylosingSpondylitisFunctional Index(BASFI),BathAnkylosingSpondylitisMetrology
Index(BASMI),radiographicprogression,numberofwithdrawalsduetoAEsandnumberofseriousAEs
Datacollectionandanalysis
Two review authors independently selected trials for inclusion, assessed the risk of bias, extracted data and assessed the quality of
evidenceformajoroutcomesusingGRADE.
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial 1
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Weincluded39studies(35RCTs,twoquasi-RCTsandtwocohortstudies);and29RCTsandtwoquasi-RCTs(n=4356)inquantitative
analysesforthecomparisons:traditionalNSAIDsversusplacebo,cyclo-oxygenase-2(COX-2)versusplacebo,COX-2versustraditional
NSAIDs,NSAIDsversusNSAIDs,naproxenversusotherNSAIDs,lowversushighdose.Mosttrialswereatunclearriskofselection
bias(n=29),althoughblindingofparticipantsandpersonnelwasadequatein24trials.Twenty-fivetrialshadlowriskofattritionbias
and29trialshadlowriskofreportingbias.Riskofbiasinbothcohortstudieswashighforstudyparticipation,andloworunclearfor
allothercriteria.Notrialsinthemeta-analysesassessedpatientswithnr-axSpA.
TraditionalNSAIDsweremorebeneficialthanplaceboatsixweeks.Highqualityevidence(fourtrials,N=850)indicatesbetterpain
reliefwithNSAIDs(painincontrolgrouprangedfrom57to64ona100mmvisualanaloguescale(VAS)andwas16.5pointslower
intheNSAIDgroup(95%confidenceinterval(CI)-20.8to-12.2),lowerscoresindicatelesspain,NNT4(3to6));moderatequality
evidence(onetrial,n=190)indicatesimproveddiseaseactivitywithNSAIDs(BASDAIincontrolgroupwas54.7ona100-point
scaleandwas17.5pointslowerintheNSAIDgroup,95%CI-23.1to-11.8),lowerscoresindicatelessdiseaseactivity,NNT3(2to
4));andhighqualityevidence(twotrials,n=356)indicatesimprovedfunctionwithNSAIDs(BASFIincontrolgroupwas50.0ona
100-pointscaleandwas9.1pointslowerintheNSAIDgroup(95%CI-13.0to-5.1),lowerscoresindicatebetterfunctioning,NNT
5(3to8)).High(fivetrials,n=1165)andmoderate(threetrials,n=671)qualityevidence(downgradedduetopotentialimprecision)
indicatesthatwithdrawalsduetoAEsandnumberofseriousAEsdidnotdiffersignificantlybetweenplacebo(52/1000and2/1000)
andNSAID(39/1000and3/1000)groupsafter12weeks(riskratio(RR)0.75,95%CI0.46to1.21;andRR1.69,95%CI0.36to
7.97,respectively).BASMIandradiographicprogressionwerenotreported.
COX-2NSAIDSwerealsomoreefficaciousthanplaceboatsixweeks.Highqualityevidence(twotrials,n=349)indicatesbetterpain
reliefwithCOX-2(painincontrolgroupwas64pointsandwas21.7pointslowerintheCOX-2group(95%CI-35.9to-7.4),NNT
3(2to24));moderatequalityevidence(onetrial,n=193)indicatesimproveddiseaseactivitywithCOX-2(BASDAIincontrolgroups
was54.7pointsandwas22pointslowerintheCOX-2group(95%CI-27.4to-16.6),NNT2(1to3));andhighqualityevidence
(twotrials,n=349)showedimprovedfunctionwithCOX-2(BASFIincontrolgroupwas50.0pointsandwas13.4pointslowerinthe
COX-2group(95%CI-17.4to-9.5),NNT3(2to4)).Lowandmoderatequalityevidence(threetrials,n=669)(downgradeddueto
potentialimprecisionandheterogeneity)indicatesthatwithdrawalsduetoAEsandnumberofseriousAEsdidnotdiffersignificantly
betweenplacebo(11/1000and2/1000)andCOX-2(24/1000and2/1000)groupsafter12weeks(RR2.14,95%CI0.36to12.56;
andRR0.92,95%CI0.14to6.21,respectively).BASMIandradiographicprogressionwerenotreported.
Therewerenosignificantdifferencesinbenefits(painonVAS:MD-2.62,95%CI-10.99to5.75; threetrials,n=669)orharms
(withdrawalsduetoAEs:RR1.04,95%CI0.60to1.82;fourtrials,n=995)betweenNSAIDclasses.Whileindomethacinuseresulted
insignificantlymoreAEs(RR1.25,95%CI1.06to1.48;11studies,n=1135),andneurologicalAEs(RR2.34,95%CI1.32to4.14;
ninetrials,n=963)thanotherNSAIDs,thesefindingswerenotrobusttosensitivity analyses.Wefoundnoimportantdifferences
inharmsbetweennaproxenandotherNSAIDs(threetrials,n=646),althoughotherNSAIDsappearedmoreeffectiveforrelieving
pain(MD6.80,95%CI3.72to9.88;twotrials,n=232).Wefoundnocleardose-responseeffectonbenefitsorharms(fivestudies,
n=1136).SinglestudiessuggestNSAIDsmaybeeffectiveinretardingradiographicprogression,especiallyincertainsubgroupsof
patients,e.g.patientswithhighCRP,andthatthismaybebestachievedbycontinuousratherthanon-demanduseofNSAIDs.
Authors’conclusions
HightomoderatequalityevidenceindicatesthatbothtraditionalandCOX-2NSAIDsareefficaciousfortreatingaxSpA,andmoderate
tolowqualityevidenceindicatesharmsmaynotdifferfromplacebointheshortterm.VariousNSAIDsareequallyeffective.Continuous
NSAIDusemayreduceradiographicspinalprogression,butthisrequiresconfirmation.
PLAIN LANGUAGE SUMMARY
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(axSpA)
InthisCochranereviewoftheeffectofNSAIDsforpeoplewithaxSpA(includingankylosingspondylitisandnon-radiographic(nr-
)axSpA),weincluded39studieswith4356people(searchupto18June2014).Onestudylookedatpeoplewithnr-axSpA.
InpeoplewithaxSpA:
TraditionalandCOX-2NSAIDsimprovepain,diseaseactivityandfunctioning(highqualityevidence)andprobablydonotresultin
morewithdrawalsduetoadverseeventsorseriousadverseeventscomparedwithplacebointheshortterm(moderatequalityevidence,
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial 2
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
assomeoutcomessufferedpotentialimprecision). Weoftendonothavepreciseinformationaboutsideeffects,particularlyforrare
butserioussideeffects.Possiblesideeffectsmayincludegastrointestinalcomplaints.Rarecomplicationsmayincludegastrointestinal
bleedingorproblemswithheartorbloodvessels.
WhatisaxSpAandwhatareNSAIDs?
AxSpAisaformofarthritisinvolvingthejointsofthepelvisorspineorboth.Itcausespainandstiffnessinthoseregionsandcanresult
indeformitiesofthespineandpoorfunctioning.
NSAIDsarecommonlyusedtoreducepainandinflammationandareconsideredfirst-linetreatmentforpeoplewithaxSpA.COX-2
NSAIDsareasubgroupofNSAIDsthatpotentiallyleadtolessgastrointestinalcomplaintsthantraditionalNSAIDs,althoughthere
isevidencethattheymayleadtoothercomplications,likeahigherriskofcardiovascularevents.
WhathappenstopeoplewithaxSpAtakingNSAIDsaftersixweeks:
PeoplewhousedatraditionalNSAIDratedtheirpaintobe16.5pointsloweronascaleof0to100(lowerscoremeanslesspain)(17%
absoluteimprovement).
-PeopleusingatraditionalNSAIDratedtheirpaintobe44points;peopleusingplacebo60.5points.
PeoplewhousedatraditionalNSAIDratedtheirdiseaseactivitytobe17.5pointsloweronascaleof0to100(lowerscoremeansless
diseaseactivity)(18%absoluteimprovement).
-PeopleusingatraditionalNSAIDratedtheirdiseaseactivitytobe37.2points;peopleusingplacebo54.7points.
PeoplewhousedatraditionalNSAIDratedtheirfunctioningtobe9.1pointsloweronascaleof0to100(lowerscoremeansbetter
functioning)(9%absoluteimprovement).
-PeopleusingatraditionalNSAIDratedtheirfunctioningtobe40.9points;peopleusingplacebo50.0points.
Thirteenpeoplelessoutof1,000stoppedtakingatraditionalNSAIDbeforetheendofthestudybecauseofsideeffects(0%absolute
difference).
-39peopleoutof1,000receivingatraditionalNSAIDstopped,comparedto52outof1,000receivingplacebo.
Onemorepersonoutof1,000hadaseriousadverseeventwhiletakingatraditionalNSAIDduringthestudy(0%absolutedifference).
-3peopleoutof1,000receivingatraditionalNSAIDhadaseriousadverseeventduringthestudy,comparedto2outof1,000receiving
placebo.
PeoplewhousedaCOX-2NSAIDratedtheirpaintobe21.7pointsloweronascaleof0to100(22%absoluteimprovement).
-PeopleusingaCOX-2NSAIDratedtheirpaintobe42.3points;peopleusingplacebo64points.
PeoplewhousedaCOX-2NSAIDratedtheirdiseaseactivitytobe22pointsloweronascaleof0to100(22%absoluteimprovement).
-PeopleusingaCOX-2NSAIDratedtheirdiseaseactivitytobe32.7points;peopleusingplacebo54.7points.
Peoplewho usedaselectiveCOX-2NSAIDratedtheir functioning tobe 13.4 points lower on ascaleof 0to 100 (13% absolute
improvement).
-PeopleusingaCOX-2NSAIDratedtheirfunctioningtobe36.6points;peopleusingplacebo50.0points.
Thirteenpeoplemoreoutof1,000stoppedtakingaCOX-2NSAIDbeforetheendofthestudybecauseofsideeffects(2%absolute
difference).
-24peopleoutof1,000receivingaCOX-2NSAIDstopped,comparedto11outof1,000receivingplacebo.
Thesame number ofpeoplehadaseriousadverse eventwhiletaking aCOX-2NSAIDor placeboduring thestudy (0%absolute
difference).
-2peopleoutof1,000receivingaCOX-2NSAIDhadaseriousadverseeventduringthestudy,comparedto2outof1,000receiving
placebo.
Non-steroidalanti-inflammatorydrugs(NSAIDs)foraxialspondyloarthritis(ankylosingspondylitisandnon-radiographicaxial 3
spondyloarthritis)(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Copyright©2015Thspondyloarthritis)(RNon-steroidalanti-in STrUadMitioMnalANSRAIYDscOomFparFedIwNithDplIacNebGofSoraFxSOpAR(ASTanHdnEr-axMSpAA)IN COMPARISON [Explanation]
eCochraneeview)flammatory ICSPneaotttemtireipvnnaegtrnsiot:sriooopnuno:t:ppptarulaatliadcetientiboito,onnh:aoplsaNptiiSetaAnlItDswithaxSpA(ASandnr-axSpA)
C d
ollabor rugs(N Outcomes Illustrativecomparativerisks* (95%CI) Relativeeffect Noofparticipants Qualityoftheevidence Comments
ation SAID (95%CI) (studies) (GRADE)
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ub fo Assumedrisk Correspondingrisk
lished raxia Placebo TraditionalNSAID
by lsp
Jo on
h d PainonVAS Themeanpainscorein The mean pain scores 850 ⊕⊕⊕⊕ Absolutepercentdiffer-
n y
W lo Scalefrom0to100mm thecontrolgroupwas in the intervention (fourstudies) high ence: 17% lower (12%
a
iley&S rthritis (Fhoilglohwer-uisp:w2otrose6)weeks 61points1 glorwoueprsw(1a2s.216.t5opo2in0t.8s tRoel2a1ti%velower) percent
ons, (ank lower) change from baseline:
L y 21%lower(16%to27%
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d Duetoadverseevents to2%more)
n
on Follow-up: 2 to 12 Relative percent differ-
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h
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xia BASDAI ThemeanBASDAIinthe ThemeanBASDAIinthe 190 ⊕⊕⊕(cid:13) Absolutepercentdiffer-
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Scale from 0 to 100 controlgroupwas interventiongroupwas (onestudy) moderate5 ence: 18% lower (12%
(higherisworse) 54.7points 17.5pointslower(11.8 to23%lower)
Follow-up:6weeks to23.1lower) Relative percent
4
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opyright©2015Thpondyloarthritis)(Ron-steroidalanti-in c2lNoh8Nwa%Ten:rlg)o3e6w(2efrroto(m149)b%7atsoel3in7e%:
eCochraneCeview)flammatoryd BS(hcAiagSlheFeIrfirsomwor0se)to 100 Tc5oh0ne.0trmopeloaginnrtosBu8pAsSFwIaisn the TtwhhaeesintmerevaenntioBnASgFroIupins 3(t5w6ostudies) ⊕hi⊕gh⊕⊕ Ae1n3bc%seol:lou9wt%eepr)leorwceenrt(d5i%ffetro-
ollab rugs Follow-up:6weeks 9.1pointslower(5.1to Relative percent
or (N 13.0lower) change from baseline:
ation.P SAIDs) 1lo7w%erl)o9wer (9%to 24%
ub fo NNT:5(3to8)10
lishedby raxialsp BASMI Seecomment Seecomment Seecomment Seecomment None of the trials in-
Jo on Scale from 0 to 10 cluded in this compari-
h d
n y (higherisworse) sonreportedBASMI
W lo
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iley&S rthritis Rsiaodniographic progres- Seecomment Seecomment Seecomment Seecomment Ncloundeedoifn tthhies ctroiamlspairni--
ons, (ank Mean change in sonreportedmSASSS
L y
td. losing mScSaAleSSfSr.om 0 to 72
s
p (higherisworse)
o
n
d
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litis Number of seriousad- 2per100011 3per1,000 RR1.69(0.36to7.97) 671 ⊕⊕⊕(cid:13) Absolutepercentdiffer-
an verseevents (1to16) (threestudies) moderate12 ence:0%more(1%less
d
n Follow-up: 6 to 12 to2%more)
o
n-r weeks Relative per-
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opyright©2015TheCochranepondyloarthritis)(Review)on-steroidalanti-inflammatory *GAArAiTsnnRbhkkaAbeylriDonlebogEvatsuihWsiaeneitosgiScorfcokSnoaimspnrl:eogtphCnaGedIr:riyasoclsoiuotsnpinsufggmiFdrrouaeeunddnpcecrtsieaisonokinndfa(teeetlhv.rIgivend.adertlee;hnlxReca;eRtmBi:veAreidSseiMkafnfrIe:acctBoitoano;tthfrNotSAhlAegnrkIiDonyu:ltoepnsrovriinnesg-nksttSaieocprnroooi(ndsadasnyldsliattiuintssdtii9M-ein5sef%)tlarioCsmlIpo)m.rgoayvtioIdnredydedxirn;umgfo;SoBAtAnSoSStDSeA:sI.m:TBohadetifhcieoAdrnrekSsytoplokosenindAginnSgkpyrloiosnskdin(yaglintiSdspiDtosnis9de5yal%isteiCsAI)ScipstiivnbiaatylsSeIndcdooernex;;thBVeAAaSSsF:sIV:uiBmsauetadhl
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ollab rugs HMiogdheqrautaeliqtyu:aFliutryt:hFeurrrtehseerarrecsheiasrcvheriysulinkleiklyeltyothoacvheaanngeimopuorrctaonntfiidmepnaccetionnthoeuresctoimnfaidteenocfeeifnfetchte.estimateof effectandmaychangetheestimate.
oration (NSAID VLoewryqlouwaliqtyu:aFliutyrt:hWereraerseeavercryhuisncveerrytaliinkealbyotouthtahveeeasntimimapteo.rtantimpactonourconfidenceintheestimateof effectandislikelytochangetheestimate.
.P s)
ublished foraxia 12AEsstsimumateeddrriseklabtiavseecdhoanngmeesabnacsoedntoronlmgreoaunp(fSinDa)lpvaailnuoesntVaAkSeninfrpolmacDeboouggaroduopsa1t9b9a4s;evalinned7er7.H2e2ij(d1e52.2040)5f.rom vanderHeijde
by lsp 2005.
Jo on 3BasedonMCIDof 15pointsona0to100pointscale.
h d
nW ylo 4Assumedriskbasedonthemedianriskinthecontrolgroups.
iley&Sons, arthritis(ank 6572EDB0sao0tsw5ime.ndgaorteanddMerdeCldIaDutieovefto1c0phoaptnoeginnettsisalboianmsaperd0ecotoins1imo0n0eadpnuoei(nSttoDs)dcaBatlAaeS.aDvAaIilainblpelaocnelybforogmroaupsiantglbeassteuldinye(N61=.71890(1).8.70) from van der Heijde
L y
td. losing 98EAsstsimumateeddrriseklabtiavseecdhoanngthesebcaosnetrdolognrmouepanfin(SaDlv)aBluAeSsFIfrionmplavacnebdoergrHoeuipjdaet2b0a0s5e.line54.12(26.99)from vanderHeijde2005.
s
po 10BasedonMCIDof 10pointsona0to100pointscale.
n
d 11Assumedriskbasedonthemeanriskinthecontrolgroups.
y
litis 12Downgraded due to potential imprecision because the 95%CI includes ’no effect’ and the upper confidence limit also
an crosses’appreciableharm’.
d
n Sincethestudiesincludedintheanalysesof thiscomparisonweremorehighqualitystudiescomparedtotheotherincluded
o
n
-r studiesinthereview,itwasdecidednottodowngradetheevidenceforstudylimitations(asassessedintheriskof bias),as
a
dio theauthorsbelievethisdidnotimportantlyaffectthequalityof theevidenceof thiscomparison.
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