Patient-reported improvements in health are maintained 2 years after completing a short course of

13 Pages·2016·1.95 MB·English

Pain
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EXTENDED REPORT O
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Patient-reported improvements in health : firs
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are maintained 2 years after completing u
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a short course of cognitive behaviour e
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therapy, exercise or both treatments 10
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for chronic widespread pain: long-term 6
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results from the MUSICIAN p
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randomised controlled trial 0
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Marcus Beasley,1 Gordon J Prescott,2 Graham Scotland,3 John McBeth,4 o
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Karina Lovell,5 Phil Keeley,5 Philip C Hannaford,6 Deborah P M Symmons,7 1
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Ross I R MacDonald,1 Steve Woby,8 Gary J Macfarlane1 F
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Tocite:BeasleyM, ABSTRACT 2
Key messages 0
PrescottGJ,ScotlandG, Objectives:TheMUSICIANstudyhaspreviously 1
etal.Patient-reported shownshort-termbenefitbutonlymarginalcost- ▸ Telephone cognitive behaviour therapy (tCBT) 5. D
improvementsinhealthare
maintained2yearsafter effectivenessfortwonon-pharmacological and exercise have been shown in systematic ow
completingashortcourseof interventionsforchronicwidespreadpain(CWP).We reviews to be associated with short-term nlo
cognitivebehaviourtherapy, wishedtodeterminetheirlong-termeffectivenessand improvement of fibromyalgia symptoms, ad
exerciseorbothtreatments cost-effectiveness. althoughthesizeofeffectsaremodest. ed
forchronicwidespreadpain: Methods:A2×2factorialrandomisedcontrolledtrial ▸ 6-month programmes of CBT delivered by tele- fro
long-termresultsfromthe basedinprimarycareintheUK.Peoplewereeligibleif phone and exercise were associated with health m
Mc2o0Un1St5rIo;C1llI:eeAd0N0t0rria0anl2.d6Ro.mMiDseOdpen thinhatedeyrcvweoennrtseiouanltgseedwdteh≥ree2ir5agy6ee-namersroanwltphitrhatecClteiWtpiohPnoefnore.rcTwohhgeincihtivtheey iarmeltchpeoriovuvignehgmbetonhttehr2etryeewaatamrsseannfttose.ratdhdeiteionndaolfbtreenaetmfitenotf, http://rm
d0o0i0:1002.61136/rmdopen-2014- behaviourtherapy(tCBT)and/oratailoredexercise ▸ tCBT was highly cost-effective and improvement dop
programme,incomparisontousualcare.Theprimary couldpartlybepredictedbypatientcharacteristics. e
n
▸ Prepublicationhistoryfor Rouetscuomltse:w8a8s4ppaetriesnotn-srewpoerrteedelicghibalneg,e44in2hweearlteh. .bm
thispaperisavailableonline. randomisedand81.7%werefollowedup24months therewasnoadvantageforpatientsreceivingboth j.co
Toviewthesefilesplease post-treatment.Incomparisontousualcare(positive interventions. m
v(histtitp:t/h/edxj.oduorin.oarlgo/n1l0in.1e136/ outcome12.8%),tCBT(35.4%;OR3.795%CI(1.8to Trialregistration number:ISRCTN67013851. on/
rmdopen-2014-000026). 8.0)),exercise(29.3%;OR2.895%CI(1.3to6.0)) Fe
andbothinterventions(31.2%;OR3.195%CI(1.3to b
ru
Received26November2014 6.0))weresignificantlymoreeffective.Therewasonly a
Accepted23December2014 asmalldecreaseineffectivenessovertimefor ry 1
iinndteinvisdeu/dalisaanbdlincgompabiinn,ehdigtrheeartmdiesntrtess.sThaonsdethwoitshemwohroe BCAhCrKoGnRicOUwNidDespread pain (CWP: defined as 6, 20
2
exhibitedpassivecopingatbaselineweremorelikelyto 3
haveapositiveoutcomewithtCBTthanpersons axial skeleton pain and contra-lateral body b
withoutthesecharacteristics.tCBTwasassociatedwith pain present for at least 3months) has a y g
thegreatestincreaseinqualityoflifeandlowestcosts. population prevalence of 11–14%.1 CWP is ue
Fornumberedaffiliationssee Costperqualityadjustedlifeyearwas£3957–£5917 the cardinal feature of fibromyalgia, one of st. P
endofarticle. dependingonmethodofanalysis. the most common reasons for referral to a ro
Conclusions:AshortcourseoftCBTforpeoplewith rheumatologist.2 Longitudinal studies of tec
CWPwaseffectivelong-termandwashighlycost- CWP and fibromyalgia demonstrate that te
Correspondenceto d
ProfessorGaryJMacfarlane; effective.Exercisewasalsoeffectivebutdelivered symptoms are persistent and long-lasting. In by
[email protected] positiveoutcomeforfewerpatientsatgreatercost,and an 11-year follow-up of 1555 patients with c
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BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 1 t.
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fibromyalgia in the USA, substantial or moderate rheumatic disease was not an exclusion criterion. D
O
symptom improvement was observed in only 10% and Participants were electronically randomised to treatment p
15% patients, respectively, while in 39%, symptoms wor- groupsinblocks,stratifiedbypainintensityanddisability en
sened.3 In afollow-up of 173 adults with CWP in the UK (Chronic Pain Grade (CPG) questionnaire14) and psy- : firs
only 15% were pain-free7years later.4 chological distress (General Health Questionnaire 12 t p
Although CWP symptoms are sometimes described as itemversion(GHQ)15)Afulldescription ofthoserando- ub
‘unexplained’, epidemiological studies over the past two misedintothetrialhasbeenreportedpreviously.12 lish
e
decades have provided important information on aeti- d
a
ology that has informed studies of management. Treatment groups s
Consistent findings in longitudinal population studies Telephone-deliveredBCBT 10
.1
are that persons with poorer mental health (anxiety, This was delivered by therapists accredited by the British 1
3
depression and general psychological distress) and who Association for Behaviour and Cognitive Psychotherapies 6
take low levels of exercise have an increased risk of who received 3days of trial-specific training, a therapist /rm
developing CWP or fibromyalgia.5–7 These risk factors manual and fortnightly clinical supervision. All sessions do
p
offer targets for intervention: Bernardy et al8 concluded were digitally recorded for use in therapist supervision. en
that cognitive behaviour therapy (CBT) resulted in Therapists mailed brief details welcoming patientsto the -20
1
increased coping with pain, reduced depressed mood study, giving a brief introduction to CBT and providing 4
and healthcare seeking behaviour; Haüser et al9 contact details. The intervention included an initial -00
reported that an aerobic exercise programme resulted assessment (45–60min), seven weekly sessions (each 00
2
in decreased pain, and had positive effects on mood, 30–45min) delivered over 6weeks, and a single session 6 o
health-related quality of life and physical fitness; and a at 3 and 6months postrandomisation. Therapists con- n
1
network meta-analysis reported improved patient out- ducted a patient-centred assessment, developed shared 8
comes for both CBTand aerobic exercise.10 However, in understanding and formulation of the participants’ Fe
b
a recent Cochrane review of CBT for fibromyalgia, the problem(s), and identified two to three patient-defined ru
a
median duration of post-treatment follow-up for CBT goals. Patients received a self-management CBT manual, ry
interventions evaluated in trials was only 6months ‘Managing Chronic Widespread Pain’, developed for the 20
1
post-treatment.11 study (available from the authors). To enable patients to 5
We have previously reported the short-term (3months make an informed choice of the form of CBT they pre- . D
o
post-treatment) results of the ‘Managing Unexplained ferred, the manual included stories of fictitious patients w
n
Symptoms (chronic widespread pain) In primary Care: using specific CBT techniques: behavioural activation lo
a
Involving traditional and Accessible New approaches’ (structured increasing of activities), cognitive restructur- de
c(MlinUicSaIlCbIAenNe)fitstrioafl.1a2n Tinhdeivseidudaelmoroncsotrmatbeidnedsig6n-mifiocnatnht isntygles)(idaenndtiflyiifnesgtyleancdhaenvgaelsua(tminagnaugninhgelpslfeuelp,thfaintikgiuneg, d from
programme of CBT delivered by telephone (tCBT) and irritability). Sessions involved implementing CBT techni- h
ttp
aHnoweexveerrc,isceostp-eroffgercatmivemnee,sscoofmpthaeredactwiviethinutesurvaelntciaornes. qtoueims,pwroorvkeimngentot,wwarhdilegolaatlesransedsspioronbslefomcussoeldvinognbraerlraipesres ://rm
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was marginal at 3months post-treatment. In view of the prevention. o
p
positive clinical results we decided to conduct a long- e
n
term (24months post-treatment), unplanned, follow-up Exercise .b
m
to determine whether clinical benefits persisted, and to Experiencedfitnessinstructorsdeliveredtheintervention j.c
o
assess longer term cost-effectiveness. We also aimed to andreceiveda1-daytrainingsessiononexerciseprescrip- m
determine whether the characteristics of participants at tion for patients with CWP. They were observed during o/
n
trial entrypredicted treatment response. induction and follow-up meetings to monitor protocol F
e
adherence. Patients received a leisure-facility gym-based b
exerciseprogrammeconsistentwithAmericanCollegeof rua
METHODS SportMedicine(ACSM)guidelinesforimprovingcardio- ry 1
A 2×2 factorial randomised controlled trial was con- respiratory fitness.16 Following an induction session, 6
ducted during 2008–2012. Trial participants, identified patients were offered six fitness instructor-led monthly , 20
2
fromtheregisteredpopulationsofeightgeneralpractices appointments for programme reassessment. Exercise 3
in Aberdeen, Scotland, and in Cheshire, England, were intensity increased until levels were sufficient to achieve by
people aged ≥25years who reported CWP according to 40–85% of heart rate reserve. The ACSM does not pre- gu
e
t(hAeCdRe)fi1n9it9io0ncirnitethrieaAfomrerfiicbarnomCyoalllgeigae,1o3faRnhdeufomratwohloicghy sfictrnibesesisnpsetcruificctoerxaenrdcipseast;ietnhte.sTehaerterianlepgroottioatceodlrbeefltewceteend st. P
ro
theyhadconsultedtheirgeneralpractitioner(GP)inthe this, allowing exercises to be changed while maintaining te
previous year. Exclusion criteria included contraindica- thegoalofimprovingcardiorespiratoryfitness.Theexer- cte
tionsto exercise, having pain that required specific alter- cise intensity range was broad, allowing individuals with d b
native treatment or not having access to a landline low fitness or those who were deconditioned to achieve y c
o
telephone (for the delivery of CBT). Comorbid goalswithlow-intensityexercise.Toavoidmusculoskeletal p
y
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2 BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 t.
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injuries and to promote compliance, initial intensity was Main treatment effects were assessed on an intention- D
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low to moderate. Patients were free to engage in add- to-treat analysis. The primary outcome was analysed p
itional exercises (eg, strength and flexibility training) to using generalised estimating equations (GEE) for longi- en
those prescribed. The recommended session duration tudinal logistic regression. A 2-way factorial regression : firs
was 20–60min. Patients completed a diary recording fre- using the outcome at end of treatment, 3 and t p
u
quencyof gym attendance, exercise duration and type of 24months post-treatment, including terms for treatment b
exercise, which was returned to the coordinating unit. interaction and treatment–time effect, was fitted. The lish
e
TheACSMguidelines recommendanexercisefrequency term for the interaction of treatments was less than one d
of 3–5days per week. This was thought to be unrealistic. (ie, the combined effects were less than multiplica- as
Instead, patients were advised to attend at least twice a tive).12 Analysis was carried out, therefore, comparing 10
week,andonnon-gymdaysengagein‘everyday’activities the threetreatment groupstoTAU. Secondaryoutcomes .11
(eg,briskwalking)toenhancecardiorespiratoryfitness. were analysed using GEE for longitudinal ordinal or 36
linear regression where appropriate, including a treat- /rm
d
Combinedtreatment ment by time interaction with four separate treatment op
e
Participants randomised to this group received both of groups. Results are presented as ORs for logistic regres- n
the above treatments concurrently. sion, proportional OR for ordinal regression and non- -20
standardised regression coefficientsfor linear regression, 14
-0
with 95% CI for each active treatment compared with 0
Treatment as usual 0
the TAU group at each time point, and for the treat- 0
Participants randomised to this group continued to 2
receiveusualcare(withoutanyrestrictions)fromtheirGP. ment by time interaction. A Bonferroni correction 6 o
allowed for multiple testing, with p values lessthan 0.004 n
1
considered statisticallysignificant. Analyses were adjusted 8
Outcome measurements F
for age, sex, baseline CPG, baseline GHQ score and e
b
Primary and secondary outcome data were collected at study centre, with analyses of secondary outcomes also ru
a
the end of treatment, and at 3 and 24months post- adjusted for baseline scores on the outcome of interest. ry
treatment, by postal questionnaire. Non-responders were In order todetermine theinfluenceofmissing follow-up 20
followed up with telephone interviews in which the data, we compared baseline data for participants who 15
primary outcome measure was recorded. The primary did and did not provide 24-month follow-up data. We . D
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outcome measure was self-reported change in health also determined how sensitive the results were to w
n
status since the start of the trial; on a 7 point scale missing follow-up data by, conservatively, assuming that lo
ranging from ‘Very much worse’through ‘No change’to ad
all persons lost to follow-up data did not have a positive e
‘rVeeproyrtmoufch‘Mbeutcther’b.eAttpero’sitoivre‘oVuetrcyommeucwhasbdeetfitenre’.dTahsias outcome on the primary measure, as well as performing d fro
analyses using imputation by chained equations, which m
measure has been used previously in trials of exercise predicts missing data based on all available data. All ana- h
forSeficbornodmayraylgioau17tcaonmdeformceharsounriecsfatwigeuree sytnhderoCmhea.1l8der lysTeos wdeerteercmoinndeupctreeddiuctsoinrgs oSfTAeTffAecstoivfetwnaerses.o25f each inter- ttp://rm
Fatigue Scale,19 20 pain (measured by the CPG), the vention, logistic regression models were fitted separately do
Vanderbilt Pain Management Inventory,21 psychological for each outcome time point, to see which baseline pe
n
distress (measured by the GHQ), the Sleep Problem factors (if any) modified treatment effectiveness. Age .b
3S6ca-Iltee,m22 SthheortTaFmorpmaHSceaallethfQorueKsitnioensinoapihreob(SiaF2336)a.n24d the was treated as a continuous variable to calculate change mj.co
in odds of treatment effectiveness for every 10years. m
Other predictors were split into two categories by the o/
Statisticalissues:sample size andanalysis median value. Four treatment groups were specified and n F
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The sample size calculation in the registered protocol models included an interaction between the baseline b
was based on change in the primary outcome measure characteristic of interest and the treatment. ORs were rua
at 3months post-treatment. Anticipated improvements calculated to compare the odds of improvement in each ry 1
in the four arms (taking account of likely effectiveness activetreatment group to TAU. Then, a separate longitu- 6
and compliance with intervention) were: treatment as dinal model was fitted foreach of the predictors of treat- , 20
2
usual (TAU) 10%, exercise only 20%, CBT only 21.3%, ment effectiveness, to assess whether the effect was the 3
b
exercise and CBT 31.3%. A total of 552 persons were same over all follow-up time points. Adjustment was y
g
deemed necessary to have at least 80% power of detect- made for the same baseline characteristics as in the u
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ipnagreddiffewriethnceTsAinU.theHoawcteivveer,intdeurveenttioonhgirgohueprs cthoman- mainanalysis. st. P
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anticipated follow-up rates during the trial, and the fact Health economic analysis te
that the trial steering committee and data monitoring The UK national tariff26 was used to assign each partici- cte
d
committee considered the original estimates (which pant with a health state utility weight based on their b
used a χ2 test with continuity correction) to be too strin- response to the EQ-5D at 24months post-treatment. y c
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gent, the trial sample sizewas reduced to 468. Reported health service resource use during the p
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BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 3 t.
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previous 6months was valued using the same unit cost time point compared with TAU (table 3). The odds of D
data used in the original analysis.27–29 Additional quality reporting a positive outcome showed a small decrease Op
e
adjusted life years (QALYs) accrued between 3 and with time for all active treatments (change in OR/ n
24months post-treatment were calculated for each par- month 0.96 to0.99). : firs
ticipant assuming a linear change in utility. This was t p
u
added to the 3-month post-treatment QALYestimate for Secondaryoutcomes b
each patient. Linear interpolation between reported The active treatment groups were generally associated lish
e
health service costs at 3 and 24months post-treatment with small improvements in each of the secondary mea- d
a
was used to impute an average quarterly cost for each sures compared with TAU (tables 4 and 5), but these s
patient for each of the five quarters not covered by data tended to decrease over time. At 24months, participants 10
collection.30 Costs and QALYs incurred beyond in the combined treatment group (in comparison to the .11
12months were discounted at the rate of 3.5% per TAU group) had significantly (p<0.004) reduced passive 36
annum inlinewith accepted practice in the UK. coping, kinesiophobia and improved SF-36 role physical; /rm
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Multivariateregressionanalysisestimateddifferencesin with significant improvement in four other SF-36 sub- o
p
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mean costs and QALYs between the three active treat- scales that did not persist after correction for multiple n
ment groups and TAU. A generalised linear model, with testing. The tCBT group showed significant improve- -20
a γ family distribution and a log link function, was speci- ment at 24months (in comparison to the TAU group) 14
fied to account for the skewed nature of the cost data. in passive coping, kinesiophobia, distress and SF-36 -00
0
Cost-effectiveness acceptability curves were constructed social function subscale but these did not persist after 0
2
using non-parametric bootstrapping and the net monet- correction for multiple testing. The exercise group 6 o
ary benefit framework, to determine the probability of showed (in comparison to the TAU group) a significant n
1
the alternative interventions being considered cost- improvement in SF-36 role emotional at 24months that 8
effective at different ceiling ratios representing society’s did not persist aftercorrection for multiple testing. Fe
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willingness to pay (WTP) per QALY (£20000–£30000 ru
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per QALY are commonly applied ceiling ratios in the Influence of missing data ry
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UK).Theanalysiswasinitially conducted forparticipants Comparing the baseline data of responders (n=361) and 0
with complete cost and QALY data at final follow-up. non-responders (n=81) at 24months post-treatment, the 15
Multiple imputation analyses, using chained equations, latter were more likely to have had CPG IV (15.5% and . D
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were used to assess the sensitivity of findings to missing 28.4%, respectively) but there were no other statistically w
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data. significant, sizeable or clinically important differences in lo
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demographic or clinical variables assessed. Assuming, e
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RESULTS conservatively, that all participants who did not provide fro
outcome data at 24months did not have a positive m
Intotal,884peoplewereidentifiedaseligibleandinvited primary outcome, the percentage of participants with a h
to participate in the trial, and 442 (50%) were rando- ttp
mised (figure 1). Those randomised had a mean age of p25o.s9it%iv,eexoeurtccioseme24.a8c%ro,sscotmhebinfeoduringtreorvuepnstiownas25tC.9B%T, ://rm
56.2years (range 25–85years), 69.5% were women and d
TAU 11%. Differences between the intervention groups o
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33.9% were in full-time employment. The CWP was and TAU remained statistically significant (OR for posi- e
n
gradedasCPGIII-IVfor30%ofparticipants.Incompari- tive outcome compared with usual care: tCBT (OR 2.8 .b
son to all those identified as eligible, those randomised (95% CI 1.4 to 5.9), exercise 2.7 (95% CI 1.3 to 5.6), mj.c
were more likely to be older, have a higher body mass o
combined 2.8 (95% CI 1.4 to 5.9)). Imputation pro- m
indexandhavemoreseverepain(p<0.05),withnoother duced results that were very similar to those reported in o/
differences found (table 1). There was no important or n
table2,withanysmalldifferencesnotaffectingtheinter- F
statistically significant difference in any of the secondary pretation of findings (data not shown). eb
outcomemeasuresacrosstreatmentgroups.12 ru
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Predictors of treatment effectiveness ry
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Primaryoutcome Potential predictors of treatment effectiveness are shown 6
, 2
At 24months post-treatment, 361 participants were fol- in table 6. Participants with more intense or disabling 0
2
lowed up (81.7%). Of these, 12.8% in the TAU group pain (as measured by CPG) or higher levels of distress 3
reported a positive outcome compared with 35.4% in (measured by GHQ) benefitted more from tCBT or by
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the tCBT group, 29.3% in the exercise group and 31.2% combined treatment (compared to those without these u
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iandjutshteed cOoRmfboinrerdepotrrteiantgmaenptosigtrivoeupout(ctoambleeco2m).paTrhede ckhinaersaicotpehriostbicias)wearnedmpoarretilcikipealynttso bweitnhefihtifgrhoemr tlCeBveTl.s of st. P
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with the TAU group were tCBT OR 3.6 (95% CI 1.7 to te
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7.6), exercise 2.5 (95% CI 1.2 to 5.4) and combined Health economics te
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treatment 2.9 (95% CI 1.4 to 6.0). Treatment costs during the intervention period, and b
y
Each treatment group was associated with statistically post-treatment follow-up costs, are summarised in c
significant increased odds of a positive outcome at each table 7. The cost-effectiveness analysis showed that all of op
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4 BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 t.
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Figure1 MUSICIANTrialCONSORTflowdiagram(TAU,treatmentasusual;tCBT,telephonecognitivebehaviouraltherapy). b
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BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 5 t.
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tCBTwas highly cost-effective in the long-term, with the D
Table1 Baselinecharacteristicsofparticipants(n=442) O
cost per QALY ranging between approximately £4k and p
Age*,years 56.3(13.0) e
£6k, depending on the method of analysis. n
GEmenpdloeyr,mfeenmtasletatus 307(69.5) A number of points should be considered when inter- : firs
Workingfull-time 154(34.8) p(rraetthinegr tohuarn rheasuvilntsg. Fairdsti,agpnaorstiiscipoafnfitsbrroempoyarltgeida)CaWndP t pub
WReotrirkeindgpart-time 14628((3125..14)) were recruited through primary care. Thus, many in the lish
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Other 78(17.6) study population had symptoms that were less severe, as d a
ChronicPainGrade evidenced by the CPG and reported work status, than s
1
I 92(20.8) would typically be seen by rheumatologists. Second, it 0
.1
II 174(39.4) could be argued that the positive results were due to 1
III 97(22.0) non-specific benefits from participating in a trial rather 36
IV 79(17.9) than the specific effects of the interventions delivered. /rm
d
GHQ* 3.2(3.6) Supporting such an interpretation is the similarity of o
p
EQ-5D* 0.69(0.19) e
positive effects across all active intervention groups n
SF-36* (including the group receiving both interventions). -20
Physicalcomponent 40.6(7.9) Againstthis interpretation, CWPhas proved verydifficult 14
Mentalcomponent 45.2(10.7) -0
Fatigue* 19.6(5.9) for rheumatologists and others to treat, and so it seems 0
0
VPMI* unlikely that such strongly positive improvements 02
Passivecoping 29.5(7.3) resulted from simply ‘attention’. We also demonstrated 6 o
Activecoping 24.9(4.2) improvements in some of the secondary outcomes n 1
Sleepscale* 9.2(5.6) related to participants’ perceptions of improvement in 8
F
TampaScaleforKinesiophobia* 35.8(5.3) their condition. If our initial results were due to non- e
b
Valuesaren(%)except*whicharemean(SD). specific effects, we would expect such effects to wane ru
a
GHQ,GeneralHealthQuestionnaire;SF-36,36-itemShortForm with time. Instead, we have observed persistence of ry
HealthQuestionnaire;VPMI,VanderbiltPainManagement 2
Inventory. strongeffects over2years.Furthermore,wehavedemon- 0
strated that persons more likely to benefit from tCBT 15
have characteristicsthat tCBTseeksto change. We recog- . D
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the active treatments were associated with an increased nise, however, that not all patients with CWP will neces- w
n
costtothe healthservice andan increaseinQALYscom- sarily be willing to consider undertaking exercise or lo
a
pared with TAU (table 8). tCBTwas associated with the participating in a CBT programme. Our results, there- de
d
lowest cost increase and highest QALY gain, and isthere- fore, can only be extrapolated to those willing to do so fro
fore dominant over the alternative active treatments. and, in this study, 70% of persons randomised to tCBT m
Based on analysis of persons who provided complete completed at least six sessions while 50% of persons ran- h
dveartsau,sthTeAUadwdaistio£n5a9l17c.oBstaspeedroQnAtLhYe rgeasiunletsdowfitthhetnCoBnT- dpoermwiseeedkt.oTehxierdrc,isteheattsetunddyedwathsengoytmpoawtelereadst ttowoutnimdeers- ttp://rm
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parametric bootstrap, tCBT was found to have an take a robust analysis of those patients who might o
p
approximately 75% chance of being the preferred strat- benefit most from each treatment. However, our strongly e
n
egy at a ceiling ratio of £20000 per QALY gained positive results for the primary outcome, and given the .b
m
(figure 2). The general pattern of results remained the current interest in stratified medicine, provide an indica- j.c
same with multiple imputation for missing data, tion of those persons with CWP who may be most likely om
although the additional cost per QALY gained for tCBT to benefit. This may be helpful given that CBT is not o/
n
reduced to£3957. available everywhere in the UK or elsewhere. Finally, we F
e
did not restrict the usual care provided by the GP. b
However,noparticipantintheTAUarmreportedreceiv- rua
DISCUSSION ing ‘talking therapy’ or exercise therapy at follow-up. ry 1
We have shown that after a short-course of tCBTand/or With no pharmacological therapies licensed in the UK 6
a personalised exercise programme, approximately for fibromyalgia (of which CWP is the cardinal feature), , 20
2
one-third of patients with CWP reported a positive management is likely to have focused on advice, investi- 3
primaryoutcome (change in condition) 24months after gation and managementof specificreported symptoms. by
end of treatment, significantly better than patients Reviews of CBT have been conducted in patients with gu
e
reeigcheitv.itnCgBTTAanUd, ewxherecriesetahpepeiamrepdrotvoembeensitmiwlaarslyobneeneifin- fiplbertoemlyyaclognias,istheonwt.evCero,chthreainrecorenvcileuwssionasgraeree tnhoatt cCoBmT- st. P
ro
cial, and there was no advantage gained from providing affects mood and pain positively.11 31 While our study te
c
both. Combined treatment, however, did appear to reported positive effects in the tCBT arm across all te
d
produce greater improvements in several secondary primaryand secondary measures 2years after the end of b
outcome measures 24months post-treatment (compared treatment, with statistically significant improvements in y c
o
to usual care and after correction for multiple testing). passive coping, kinesiophobia, distress and SF-36 social p
y
rig
h
6 BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 t.
Pain
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Table2 Primaryandsecondaryoutcomesat24monthspost-treatment O
p
TAU tCBT Exercise Combined e
n
N=94 N=82 N=92 N=93 : firs
Primaryoutcome:globalchangeinhealthsinceenteringtrial t p
Originaldata ub
Verymuchbetter 3(3.2) 5(6.1) 5(5.4) 10(10.8) lis
h
Muchbetter 9(9.6) 24(29.3) 22(23.9) 19(20.4) e
d
Alittlebetter 14(14.9) 15(18.3) 16(17.4) 17(18.3) a
s
Nochange 31(33.0) 21(25.6) 22(23.9) 19(20.4) 1
0
Alittleworse 21(22.3) 9(11.0) 16(17.4) 18(19.4) .1
Muchworse 7(7.5) 8(9.8) 9(9.8) 10(10.8) 13
6
Verymuchworse 9(9.6) 0 2(2.2) 0 /rm
Dichotomisedoutcome
d
Muchbetter/verymuchbetter 12(12.8) 29(35.4) 27(29.3) 29(31.2) op
e
Lessthanmuchbetter 82(87.2) 53(64.6) 65(70.7) 64(68.8) n
Secondaryoutcomes -2
0
CPG 14
0—Nopain 14(19.4) 12(18.2) 10(14.1) 10(13.5) -0
0
I—Lowdisability,lowintensity 18(25.0) 22(33.3) 23(32.4) 29(39.2) 0
0
II—Lowdisability,highintensity 22(30.6) 20(30.3) 16(22.5) 21(28.4) 26
III—Highdisability,moderatelylimiting 11(15.3) 8(12.1) 15(21.1) 8(10.8) o
n
IV—Highdisability,severelylimiting 7(9.7) 4(6.1) 7(9.9) 6(8.1) 1
8
GHQ* 3.0(3.3) 2.2(3.4) 2.6(3.7) 3.0(3.7) F
e
EQ-5D* 0.63(0.32) 0.73(0.24) 0.71(0.24) 0.68(0.24) b
SF-36*(all1–100)† ru
a
Generalhealth 56.2(21.3) 60.4(20.1) 59.9(22.3) 61.5(23.3) ry
2
Physicalfunction 59.2(31.9) 66.9(26.8) 68.9(25.9) 68.3(24.8) 0
1
Rolephysical 59.7(30.7) 63.3(27.0) 62.9(25.2) 68.4(29.3) 5
Vitality 45.0(22.1) 50.6(21.9) 49.8(20.0) 49.2(22.8) . D
o
Socialfunction 68.5(28.2) 74.8(26.3) 71.4(26.1) 76.2(25.5) w
n
Roleemotional 73.7(27.3) 76.5(26.4) 79.7(23.2) 74.1(29.3) lo
Fatigue(0–42)* 19.1(7.3) 17.8(6.6) 17.8(5.8) 17.6(6.9) ad
e
VPMI* d
Passivecoping(11–55) 29.4(8.9) 25.8(8.4) 27.5(8.8) 25.3(8.2) fro
Activecoping(7–35) 24.5(4.6) 25.2(4.2) 25.1(3.3) 25.8(4.4) m
Sleepscale*(0–20) 9.7(5.9) 9.4(6.0) 8.8(5.2) 8.3(6.0) http
TampaScaleforKinesiophobia*(17–68) 36.2(7.2) 33.3(5.7) 34.1(7.6) 32.9(7.8) ://rm
Valuesaren(%)except*whicharemean(SD).
†BodilyPainscoresnotavailableduetoprintingerroronquestionnaire. do
p
CPG,ChronicPainGradequestionnaire;GHQ,GeneralHealthQuestionnaire;SF-36,36itemShortFormHealthQuestionnaire;TAU, e
treatmentasusual;tCBT,telephonecognitivebehaviouraltherapy;VPMI,VanderbiltPainManagementInventory. n.b
m
j.c
o
m
o/
n
F
e
Table3 Estimationsoftreatmenteffectivenessatendoftreatment,3and24monthspost-treatmentcalculatedfrom b
ru
longitudinalmodel(adjustedORs*,95%CIsandpvalues) a
ry
Endoftreatment 3monthspost-treatment 24monthspost-treatment ChangeinOR/month 1
6
tCBT 5.0 4.8 3.6 0.99 , 2
0
(2.4to10.6) (2.4to9.7) (1.7to7.6) (0.95to1.02) 2
3
<0.001 <0.001 0.001 0.410 b
y
Exercise 4.6 4.3 2.5 0.98 g
u
(2.2to9.6) (2.1to8.5) (1.2to5.4) (0.94to1.01) e
s
<0.001 <0.001 0.015 0.147 t. P
Combinedtreatment 6.7 6.0 2.9 0.96 ro
(3.3to13.9) (3.1to11.9) (1.4to6.0) (0.93to0.997) te
c
<0.001 <0.001 0.006 0.035 te
d
*Resultsofthefour-grouplongitudinallogisticregressionmodel,adjustingforage,sex,centre,andbaselineCPGandGHQscores,including b
atermfortreatment–timeinteraction. y c
CPG,ChronicPainGradequestionnaire;GHQ,GeneralHealthQuestionnaire;tCBT,telephonecognitivebehaviouraltherapy. o
p
y
rig
h
BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 7 t.
RMD Open
R
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D
Table4 Treatmenteffectiveness,secondaryoutcomes(valuesareunstandardisedcoefficientsexceptCPG,whichare O
p
proportionalORs)* e
n
Etrneadtmofent 3pomsot-ntrtehastment 2p4osmt-otrnetahtsment iTnrteeartamcteinotn–t(ismloepe) : firs
t p
CPG ub
tCBT 0.4† 0.5† 0.7 1.02 lis
h
(0.3to0.8) (0.3to0.8) (0.3to1.3) (0.99to1.05) e
d
Exercise 0.7 0.8 1.3 1.02 a
s
(0.5to1.1) (0.5to1.2) (0.7to2.4) (0.99to1.05) 1
Combinedtreatment 0.5† 0.5‡ 0.9 1.03 0.1
(0.3to0.8) (0.3to0.8) (0.4to1.8) (1.00to1.06) 13
6
GHtCQBT −1.0‡ −1.0‡ −1.0‡ 0.00 /rm
d
(−1.8to−0.3) (−1.8to−0.3) (−1.9to−0.1) (−0.03to0.04) op
Exercise −0.9‡ −0.9‡ −0.5 0.02 en
(−1.7to−0.2) (−1.6to−0.2) (−1.4to0.3) (−0.02to0.05) -2
0
Combinedtreatment −1.0‡ −0.8‡ 0.0 0.04‡ 14
(−1.7to−0.2) (−1.5to−0.1) (−0.9to0.9) (0.00to0.08) -0
0
Fatigue 0
0
tCBT −2.6‡ −2.4‡ −1.0 0.06 26
(−4.4to−0.7) (−4.1to−0.6) (−3.0to1.1) (−0.01to0.14) o
n
Exercise −2.4‡ −2.2‡ −1.2 0.05 1
8
(−4.1to−0.7) (−3.9to−0.6) (−3.2to0.8) (−0.02to0.12) F
Combinedtreatment −4.4† −4.0† −1.5 0.12† eb
(−6.1to−2.6) (−5.7to−2.3) (−3.5to0.5) (0.04to0.20) ru
a
VPMIpassivecoping ry
tCBT −2.0‡ −2.0‡ −2.7‡ −0.03 20
(−3.7to−0.2) (−3.7to−0.4) (−4.7to−0.7) (−0.10to0.04) 15
Exercise −2.0‡ −2.0‡ −1.3 0.03 . D
o
(−3.6to−0.3) (−3.5to−0.3) (−3.2to0.6) (−0.04to0.10) w
Combinedtreatment −3.1† −3.1† −3.1† 0.00 nlo
(−4.7to−1.5) (−4.7to−1.5) (−5.0to−1.2) (−0.07to0.07) ad
e
VPMIactivecoping d
tCBT 0.8 0.8 0.8 0.00 fro
(−0.1to1.7) (0.0to1.6) (−0.3to1.8) (−0.05to0.04) m
Exercise 1.1‡ 1.1‡ 0.7 −0.02 http
Combinedtreatment (01..33†to2.0) (10..33†to1.9) (−00..38to1.8) (−−00..0062to0.03) ://rm
(0.5to2.1) (0.5to2.0) (−0.2to1.8) (−0.07to0.02) do
p
Sleepproblems e
n
tCBT −1.8‡ −1.7‡ −0.8 0.04 .b
Exercise (−−13..20‡to−0.6) (−−12..28‡to−0.5) (−−20..39to0.6) (−00..0021to0.10) mj.co
m
Combinedtreatment (−−12..54‡to−0.1) (−−12..43‡to−0.1) (−−20..38to0.5) (−00..0043to0.07) on/
(−2.6to−0.3) (−2.5to−0.2) (−2.2to0.6) (−0.03to0.08) F
e
TSK bru
tCBT −1.4 −1.5 −1.9‡ −0.02 a
(−3.0to0.1) (−3.0to0.0) (−3.6to−0.2) (−0.08to0.04) ry 1
Exercise (−−31..05to0.0) (−−21..94to0.0) (−−21..92to0.5) (−00..0041to0.07) 6, 20
Combinedtreatment −2.4† −2.5† −2.6† −0.01 23
(−3.9to−1.0) (−3.9to−1.0) (−4.3to−0.9) (−0.06to0.05) by
*Comparisongroup—treatmentasusual.Allmodelsareadjustedforage,sex,centre,baselineCPGandGHQscores,andbaselinelevelsof gu
e
outcomeofinterest. s
†‡pp<<00..00054.,withcorrectionformultipletesting. t. Pro
CPG,ChronicPainGradequestionnaire;GHQ,GeneralHealthQuestionnaire;TAU,treatmentasusual;tCBT,telephonecognitive te
behaviouraltherapy;TSK,TampaScaleforKinesiophobia;VPMI,VanderbiltPainManagementInventory. c
te
d
b
y
c
o
p
y
rig
h
8 BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 t.
Pain
R
M
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Table5 Treatmenteffectiveness,secondaryoutcomes(SF-36*)(valuesareunstandardisedcoefficients)† O
p
Endof 3months 24months Treatment–time e
n
treatment post-treatment post-treatment interaction(slope) : firs
SF36—generalhealth t p
tCBT 2.4 2.7 4.4 0.08 ub
(−1.7to6.5) (−1.3to6.6) (−0.2to9.1) (−0.09to0.26) lis
h
Exercise 2.5 2.7 4.0 0.06 e
d
(−1.5to6.4) (−1.1to6.5) (−0.6to8.5) (−0.11to0.23) a
s
Combinedtreatment 5.1‡ 5.1‡ 5.1‡ 0.00 1
(1.2to9.0) (1.3to8.9) (0.6to9.6) (−0.17to0.17) 0.1
SF36—physicalfunction 13
tCBT (−03..95to7.9) (−03..85to7.7) (−13..73to8.3) (−−00..1091to0.17) 6/rm
d
Exercise 6.4§ 6.2§ 4.7 −0.07 op
(2.2to10.6) (2.1to10.3) (−0.1to9.5) (−0.24to0.10) en
Combinedtreatment 8.8§ 8.5§ 6.2‡ −0.11 -2
0
(4.6to13.0) (4.4to12.5) (1.4to10.9) (−0.28to0.06) 14
SF36—rolephysical -0
0
tCBT 5.8‡ 5.7‡ 4.6 −0.05 0
0
(0.2to11.5) (0.3to11.1) (−2.0to11.2) (−0.31to0.21) 26
Exercise 4.4 4.3 3.5 −0.04 o
n
(−1.1to9.8) (−0.9to9.5) (−2.9to9.9) (−0.29to0.22) 1
8
Combinedtreatment 7.7‡ 8.0§ 9.8§ 0.08 F
(2.3to13.1) (2.8to13.1) (3.4to16.1) (−0.17to0.34) eb
SF36—vitality ru
a
tCBT 5.4‡ 5.4‡ 5.1 −0.01 ry
(0.8to10.1) (0.9to9.8) (−0.3to10.5) (−0.22to0.19) 20
1
Exercise 2.6 2.7 4.0 0.06 5
(−1.9to7.0) (−1.5to7.0) (−1.2to9.3) (−0.14to0.26) . D
o
Combinedtreatment 5.0‡ 5.1‡ 5.5‡ 0.02 w
(0.6to9.4) (0.8to9.4) (0.3to10.7) (−0.18to0.22) nlo
SF36—socialfunction ad
tCBT 7.4‡ 7.4‡ 7.3‡ −0.01 ed
(1.9to12.9) (2.2to12.6) (0.8to13.7) (−0.27to0.26) fro
Exercise 7.7‡ 7.0‡ 2.5 −0.22 m
(2.4to12.9) (2.0to12.0) (−3.8to8.7) (−0.47to0.04) http
Combinedtreatment (16..47‡to11.9) (61..88‡to11.8) (17..68‡to14.0) (−00..2015to0.30) ://rm
SF36—roleemotional do
p
tCBT 8.3§ 7.7§ 3.2 −0.21 e
n
(2.8to13.8) (2.5to12.8) (−3.4to9.7) (−0.49to0.07) .b
Exercise (39..91§to14.4) (83..88§to13.7) (06..14‡to12.8) (−−00..1318to0.16) mj.co
m
Combinedtreatment (28..80§to13.2) (72..12‡to12.0) (−51..30to7.4) (−−00..2596‡to0.02) on/
F
*ThecombinedscalesoftheSF-36arenotavailableduetoaprintingerrorinthefollow-upquestionnaire. e
†Comparisongroupistreatmentasusual.Valuesareunstandardisedcoefficientswith95%CIs.Allmodelsareadjustedforage,sex,centre, bru
baselineCPGandGHQscores,andbaselinelevelsofoutcomeofinterest. a
‡p<0.05. ry
§p<0.004,withcorrectionformultipletesting. 16
CPG,ChronicPainGradequestionnaire;GHQ,GeneralHealthQuestionnaire;tCBT,telephonecognitivebehaviouraltherapy;SF-36,36-item , 2
ShortFormHealthQuestionnaire. 0
2
3
b
y
g
function subscale (compared to TAU) at p<0.05, none outcomes are maintained long after such a programme u
met the more stringent statistical significance cut-off has finished and that long-term improvements in es
after correction for multiple testing. Most of the evi- patients with fibromyalgia due to increased physical t. P
ro
dence to date on the effectiveness of exercise relates to activity are maintained regardless of whether activity te
fibromyalgia. Our study extends this evidence of benefit levels return to pretreatment levels afteractive treatment cte
to persons with CWP and it provides evidence that the has finished.32 It has been demonstrated in a recent d b
benefit is long-lasting. It has previously been shown that meta-analysis that community-deliverable exercise pro- y c
o
the effects of an exercise programme on psychological grammes are effective for pain and physical function in p
y
rig
h
BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 9 t.
RMD Open
R
M
D
Table6 Predictorsoftreatmenteffectiveness O
p
Monthspost-treatment Longitudinal en
0* 3 24 adjustedmodel : firs
Gender t p
u
Malevsfemale b
TAU 1 1 1 1 lis
h
tCBT 0.5(0.1to3.9) 1.6(0.2to11.5) 0.2(0.0to1.5) 0.4(0.1to2.1) ed
Exercise 0.6(0.1to4.2) 0.8(0.1to5.6) 0.2(0.0to2.1) 0.4(0.1to1.7) a
s
Combined 0.5(0.1to3.7) 0.8(0.1to5.4) 0.2(0.0to2.3) 0.4(0.1to1.8) 1
0
CPG .1
1
3/4vs1/2 3
6
TAU 1 1 1 1 /rm
tCBT 1.2(0.2to8.4) 3.5(0.3to35.4) 11.8(1.2to115.8) 4.8(0.9to25.6) d
o
Exercise 0.9(0.1to6.2) 2.9(0.3to30.0) 5.3(0.5to52.5) 3.4(0.6to17.9) p
e
Combined 2.3(0.0to15.1) 10.6(1.1to105.6) 8.9(0.9to86.8) 8.3(1.6to43.4) n
-2
Age 0
1
Per10years 4
TAU 1 1 1 1 -00
0
tCBT 1.3(0.6to2.8) 1.1(0.5to2.1) 1.5(0.8to2.7) 1.2(0.7to2.0) 0
2
Exercise 2.2(1.1to4.6) 1.3(0.7to2.7) 0.9(0.5to1.7) 1.4(0.8to2.2) 6
Combined 2.5(1.2to5.1) 1.5(0.8to3.0) 1.2(0.7to2.2) 1.6(0.98to2.6) on
GHQ12 1
8
3–12vs0–2 F
e
TAU 1 1 1 1 b
ru
tCBT 3.4(0.5to20.8) 4.0(0.7to23.0) 7.7(1.5to40.7) 5.6(1.5to21.2) a
Exercise 0.8(0.1to4.6) 1.7(0.3to10.0) 4.5(0.9to23.6) 2.3(0.6to8.5) ry
2
Combined 1.5(0.2to8.5) 1.5(0.3to8.4) 6.7(1.3to34.7) 3.2(0.9to11.9) 0
1
Fatigue 5
19–40vs8–18 . D
o
TAU 1 1 1 1 w
n
tCBT 0.6(0.1to4.0) 0.7(0.1to3.7) 1.7(0.4to8.2) 1.0(0.3to3.8) lo
a
Exercise 0.2(0.0to1.7) 0.4(0.1to2.6) 0.8(0.2to4.0) 0.6(0.2to2.1) d
e
Combined 1.1(0.2to7.8) 1.4(0.3to8.0) 4.5(0.9to21.8) 2.7(0.7to9.6) d
Passivecoping fro
m
30–52vs18–29 h
TAU 1 1 1 1 ttp
tECxBeTrcise 11..50((00..21ttoo170.0.3)) 20..25((00..41ttoo122.9.8)) 12..11((00..24ttoo51.01.)4) 01..86((00..24ttoo25..97)) ://rm
d
Combined 3.7(0.6to24.7) 2.2(0.4to11.9) 1.6(0.3to7.5) 2.1(0.6to7.5) o
p
Activecoping en
26–35vs10–25 .b
m
TAU 1 1 1 1 j.c
tCBT 0.9(0.1to5.5) 0.6(0.1to3.5) 1.6(0.3to7.1) 1.0(0.3to3.4) o
m
Exercise 2.2(0.4to13.5) 1.5(0.3to8.7) 1.7(0.4to7.5) 1.7(0.5to6.1) o/
Combined 0.7(0.1to4.2) 0.6(0.1to3.2) 0.3(0.1to1.5) 0.7(0.2to2.4) n
F
Sleepproblems e
10–20vs0–9 bru
TAU 1 1 1 1 ary
tCBT 1.5(0.2to9.3) 1.0(0.2to5.9) 2.9(0.6to14.1) 1.8(0.5to6.5) 1
6
Exercise 1.9(0.3to11.1) 2.1(0.4to12.2) 2.5(0.5to11.8) 2.4(0.7to8.5) , 2
Combined 1.2(0.2to7.2) 0.9(0.2to5.0) 1.0(0.2to5.2) 1.1(0.3to3.9) 0
2
TSK 3
b
37–57vs21–36 y
g
TAU 1 1 1 1 u
e
tCBT 2.0(0.3to13.8) 3.7(0.6to24.3) 10.6(1.7to66.3) 4.7(1.1to20.5) s
Exercise 2.4(0.4to16.3) 2.6(0.4to17.3) 1.8(0.3to11.8) 2.8(0.7to12.1) t. P
Combined 3.9(0.6to26.6) 2.6(0.4to16.6) 3.7(0.6to23.1) 3.6(0.8to15.1) ro
te
*ORswith95%CIs. cte
Italictypefaceindicatesstatisticalsignificance. d
CPG,ChronicPainGradequestionnaire;GHQ,GeneralHealthQuestionnaire;TAU,treatmentasusual;tCBT,telephonecognitive b
y
behaviouraltherapy;TSK,TampaScaleforKinesiophobia. c
o
p
y
rig
h
10 BeasleyM,etal.RMDOpen2015;1:e000026.doi:10.1136/rmdopen-2014-000026 t.