The influences of psychosocial factors on functional impairment have been investigated by researchers working on the NOAR cohort. Recently, Camacho and colleagues (2012) published evidence that ‘learned helplessness’, a psychological state in which the subject feels unable to control the course of their disease, is associated with worse function in patients with inflammatory polyarthritis. Using data from 447 NOAR cases with available HAQ data, they described a median increase in HAQ score (where the maximum possible score was 3) of 1.12 (95% CI 0.82, 1.41) for those with high, compared to ‘normal’ learned helplessness. Furthermore, a similar effect was seen in those with low, compared to normal learned
helplessness, with a median decrease of 0.39 units (95% CI -0.69, -0.10). The authors proposed that learned helplessness mediated their observed association of social deprivation with poor functional outcome. The impact of psychosocial factors was also considered by Drossaers–Bakker et. al. (1999), in the previously mentioned 12 year study involving 112 females with RA. Psychosocial functioning was measured using a combination of
assessments including components of the Dutch version of the arthritis impact measurement scale 2 and parts of the RAND-36 measure of health related quality of life. In a multivariable regression model that controlled for the effects of age, disease duration, disease activity, (radiological) joint destruction, pain VAS and comorbidity, psychosocial functioning at 12 years was a significant indicator of HAQ at 12 years.
1.8.4.4 Smoking
The relationship between smoking and susceptibility to RA is well
documented, as is the interaction between smoking and HLA-DRB1 shared epitope alleles, which was discussed in Section 1.4.2. There is some
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evidence that smoking is associated with worse functional outcome in RA. Masdottir et. al. (2000) reported increased median HAQ values associated with heavy smoking (≥20 pack years) in one study of 63 women with RA: median HAQ in heavy smokers 1.1, compared to 0.5 in smokers of <20 pack years (p = 0.002). This effect was also seen in a retrospective analysis of data from BRASS, where current smoking was associated with higher mean mHAQ one year later (Lu et al., 2014). Both of these studies were
retrospective, using data from patients with established RA. In Mansdottir’s study, the disease duration ranged from 5 to 21 years and in the analysis of the BRASS data, mean disease duration was 15 years. These results may have been confounded by radiological damage, as smokers are more likely to have antibodies to citrullinated peptides, which in turn may increase the risk of erosive damage. Lu et al. (2014) also investigated the effects of alcohol consumption on functional outcome in RA and found that compared to cases who consumed no alcohol, mHAQ was significantly lower in cases who consumed 5.0 to 10.0g of alcohol per day. Their analysis controlled for potential confounders, including education level (as a marker of socio-
economic status) and autoantibody status.
1.8.4.5 Obesity
Obesity was also investigated by the NOAR team who reported that morbid obesity (BMI ≥35 kg/m2
) was associated with worse HAQ score in their study of 1246 patients with inflammatory polyarthritis, of whom 87 (7%) were morbidly obese (Humphreys et al., 2013b). In an analysis that controlled for the effects of age, gender, DAS28, smoking and treatment, the relationship between morbid obesity and HAQ tertile was described by an OR of 1.94 (95% CI 1.17, 3.24).
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Table 1-6 Studies investigating predictors of disability in rheumatoid arthritis
Prospective studies of short-term(≤2years)disability
Authors Date Subjects Outcome
measure(s)
Outcome times Predictors of disability
Limitations
(Jansen et al.) 2000 133 untreated prospective
outpatients meeting ACR criteria for RA,
<3 years symptom duration HAQ (DI) dichotomised into ‘less disabled’ (<median value) or ‘more disabled’ (>median value)
Baseline High DAS28 at
baseline High CRP at baseline
Both predictors and outcomes dichotomised for regression analyses, limiting power
1 year Baseline HAQ
Baseline pain VAS
(Quinn et al.) 2006 298 cases with either
CTD (116) or RA
according to ACR criteria (182)
HAQ (DI) -quartiles 1 and 2 years Baseline HAQ
RF positivity ACPA positivity in RF negative RA patients (n=67)
Study population not exclusively RA. Predictors of disability not main study outcome.
(Graell et al.) 2009 105 cases enrolled onto
an open label study using step-up treatment with Gold and MTX. ACR criteria for RA were met, <24 months’ symptom duration at baseline mHAQ, dichotomised into 0= no disability and >0 = disability
2 years Older age
RF positive
Baseline mHAQ>0
Dichotomised outcome variable limited power. Where cases dropped out, they were not included in analysis, which is a potential source of bias.
Problems associated with mHAQ include less sensitivity to change and increased floor effect compared to HAQ-DI.
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Table 1-6 continued
Authors Date Subjects Outcome
measure(s)
Outcome times Predictors of disability
Limitations
(Camacho et al.) 2012 553 consecutive cases
with recent onset IP presenting to primary care (NOAR cohort) Symptom duration less than 2 years.
HAQ (DI) - continuous
Baseline Greater social
deprivation and learned helplessness. Learned helpless possibly mediated the relationship between deprivation and HAQ
Area level deprivation used (not person level)
(Dirven et al.) 2012 497 patients from the
Dutch BeSt study. Treatment naïve, recent onset RA, meeting ACR criteria
HAQ (DI),
dichotomised into HAQ ≥1 or HAQ<1
3 months Baseline HAQ
Baseline Pain Baseline RAI Less aggressive study treatment group (Baseline RF, ACPA and presence of erosions were not predictive of disability)
Dichotomised outcome variable and some predictor variables reduced power.
This study was a post-hoc analysis from a
randomised study of different treatment method for RA.
(Humphreys et al.) 2013 1246 consecutive cases
with recent onset IP presenting to primary care (NOAR cohort) Symptom duration less than 2 years
HAQ (DI)- divided into tertiles
Baseline Highest HAQ tertile
associated with morbid obesity (BMI ≥35)
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Table 1-6 continued
Prospective studies of long-term (> 2 years) disability
Authors Date Subjects Outcome
measure(s)
Outcome times Predictors of disability
Limitations
(Drossaers-Bakker et al.) 1999 112 consecutive female
patients diagnosed with RA at the Leiden medical clinic from 1982 to 1986 HAQ (DI) – continuous Baseline, 3, 6 and 12 years Concurrent disease activity, Concurrent radiological damage (at 12 years), Psychosocial parameters Related to problems associated with the use of HAQ-DI as a continuous variable.
(Young et al.) 2000 732 consecutive
outpatients with RA according to ACR criteria. (ERAS)
Functional grades i- iv
5 years Female gender
HAQ>1 at baseline
Dichotomised outcome variable limited power. Potential bias as cases who dropped out not included in analysis. Requirement for aids
/ appliances/ home modifications
5 years Female gender
HAQ>1 at baseline Age >60 years at presentation
(Combe et al.) 2003 191 consecutive
outpatients with RA according to ACR criteria, DMARD naïve, diagnosed less than 1 year
previously
HAQ (DI) - continuous
5 years Baseline HAQ,
ESR,CRP, RAI and presence of
erosions.
(Sex, age, RF and HLA class II alleles did not predict disability)
Related to problems associated with the use of HAQ-DI as a continuous variable.
(Harrison et al.) 2005 466 cases from the UK
BROSG trial. Disease duration >5 years, ACR criteria for RA were met.
HAQ (DI) - continuous
Baseline Increased area
level social deprivation
Assumed a linear change in HAQ over time. Treated HAQ as a continuous variable Analysis limited to area- level social deprivation.
3 years Increased area
level social deprivation
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Table 1-6 continued
Authors Date Subjects Outcome
measure(s)
Outcome times Predictors of disability
Limitations
(Camacho et al.) 2011 3666 consecutive cases
with recent onset IP presenting to primary care. (NOAR cohort)
HAQ (DI) - continuous
Baseline, 1,5,10,15 years
Female gender (all time points) Late onset IP (>75 years age compared to <55 years) Related to problems associated with the use of HAQ-DI as a continuous variable. Attrition, as expected with long term follow up.
(van den Broek et al.) 2012 465 patients from the
Dutch BeSt study. Treatment naïve, recent onset RA, meeting ACR criteria
HAQ (DI)- continuous
8 years Rapid radiological
progression in the first year.
Related to problems associated with the use of HAQ-DI as a continuous variable
(Combe et al., 2013) 2013 573 patients with possible
early RA (ESPOIR cohort)
HAQ (DI) dichotomised
according to whether above or below meadian value
5 years Baseline HAQ
Older age Female gender Baseline pain VAS
Dichotomised outcome variable reduced power. Cohort had early
inflammatory arthritis rather than RA
(Norton et al.) 2013 1460 cases with RA, from
ERAS Symptoms <2 years HAQ-(DI)-continuous Baseline to 10 years, described as 4 distinct trajectories of change (classes) Worse prognostic class predicted by: Female gender Lower education level Increased radiographic damage at 3 years (No difference in RF, ANA, SE, year of first visit, or whether biologics used)
Related to problems associated with the use of HAQ-DI as a continuous variable. Attrition, as expected with long term follow up.
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ACPA, anti citrullinated peptide antibody; ACR, American College of Rheumatology; ANA, Anti nuclear antibodies; BeSt, Behandel Straregieen; BMI, body mass index; BROSG, British Rheumatoid Outcome Study Group; CRP, C-reactive protein; CTD, connective tissue disease; DAS28, disease activity score based upon counts of 28 joints; DMARD, disease modifying anti- rheumatic drug; ERAN, Early Rheumatoid Arthritis Network; ERAS, Early Rheumatoid Arthritis Study; ESPOIR, Etude et Suivi des POlyarthritis IndiffeRencieesˑ ESR, erythrocyte sedimentation rate; HAQ (DI), health assessment questionnaire (disability index); HLA, Human leucocyte antigen; IP, inflammatory polyarthritis; mHAQ, modified health assessment questionnaire; MTX, Methotrexate; NOAR, NOrfolk Arthritis Register; RA, rheumatoid arthritis; RAI, Ritchie articular index; RF, rheumatoid factor; SE, HLA-BRB1 shared epitope; UK, United Kingdom; VAS, visual analogue score.
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1.8.5 The relationship between disease activity and disability in