Chronic gout is associated with a detrimental effect on HRQOL [4–7
]. Our study suggests that chronic long-term therapy (majority on ULT) and daily colchicine started for chronic gout (to a predefined goal of serum uric acid level of <6
mg/dl) is associated with reduction in gout flares and improvement in HRQOL. This effect was seen at 1 year and maintained at 2 years. We also show in a small number of patients (n
7) that daily colchicine therapy is associated with improvement in HRQOL.
SF-36 is a generic HRQOL (i.e. the concepts are not specific for any age, disease or treatment group) and is proposed as an outcome measure for clinical trials in gout [20
]. Since generic HRQOL measures are generally less sensitive to change in a specific disease, disease-specific HRQOL instruments have been proposed to capture smaller differences and smaller changes over time and have more face validity. Gout assessment questionnaire is an example of disease-specific measure for gout [21
]. Being a generic HRQOL, one of the concerns is that the SF-36 scales’ scores may be reflecting associated comorbidities (such as hypertension, diabetes and coronary heart disease) seen in chronic gout and not due to gout per se
. This was evident in a single-centre study from the USA, where 80 patients with gout were interviewed and health utilities were assessed [5
]. Health utilities assess the value of desirability of the health state. Although patients had marked physical limitations and co-existing comorbidities, gout per se
was associated with small disutility. Also, it is conceivable that the co-existing comorbidities may limit responsiveness to change of SF-36 as improvement in gout may not have a clinically meaningful improvement in generic HRQOL. However, our study convincingly shows that physical scales of SF-36 are sensitive to change at the end of the 12-month period in our observational study; scales of bodily pain, role physical and SF-36 PCS showed moderate-to-large effect sizes. In addition, small-to-moderate effect size improvements were seen in the remaining five scales. The scales relating to mental health and MCS had negligible-to-small effect sizes that are likely due to the ceiling effect. In other words, adjusted scores for mental scales and MCS were normal or near normal to the general population as compared with the physical health scales, which were significantly lower than those of the general population (). Our data are substantiated by two large randomized controlled trials using pegloticase (presented as abstracts), which have shown clinically meaningful and statistically significant improvement in SF-36 scales and summary scores. Based on these and other published data [4–7
], SF-36 meets OMERACT filters of feasibility, reliability and validity and endorsed at an outcome measure [22
As hypothesized, patients with the presence of tophi, comorbidities, polyarticular disease and radiographic damage had lower SF-36 scores and this provides construct validity of the SF-36 (). In a large study of US veterans, patients with comorbidities reported greater decrements in their SF-36 scores [6
]. Another large observational study from the USA assessed treatment-failure gout population and showed decrements in the SF-36 scales and SF-36 PCS scores, and comorbidities were associated with worse physical functioning [4
In our multivariable models predicting improvement in SF-36 scales and summary scores (defined as ≥MCID scores), reduction in flares over 12 months was independently associated with improvements in the three SF-36 scales (bodily pain, physical functioning and role physical) at 1 year. Change in serum uric acid was not associated with an improvement in HRQOL. Since serum uric acid levels of <6
mg/dl are associated with the decline in number of flares [10
], and greater frequency and intensity of flares are associated with poor HRQOL [7
], we believe the goal of therapy should be to reduce uric acid levels <6
mg/dl. Although presence of tophi, comorbidities and polyarticular joint involvement were associated with poor HRQOL, they did not predict an improvement in HRQOL in the multivariable models.
We compared our SF-36 data with other publications assessing SF-36 in chronic gout observational studies (). In general, patients with chronic gout had marked decrements in their SF-36 PCS scores (ranging from 32.2 to 40.3), but surprisingly near-normal SF-36 MCS scores (ranging from 46.6 to 52.2). This has also been seen in other chronic arthritides such as RA and scleroderma [23
] and is likely related to psychological adjustment to their chronic disease. It is likely that patients with recurrent or recent attacks will lead to lower SF-36 MCS scores. This was shown in a US cohort study where recurrent gout attacks over the past year or having an attack over the past 3 months was associated with lower SF-36 MCS scores [7
Observational studies in gout reporting SF-36 summary scores
We also assessed ceiling and floor effects of the SF-36 scales. Ceiling effects are important as they can limit the responsiveness to change because subjects, who have achieved the maximum scores, cannot improve any further. Ours and another US study [5
] showed low floor effects in the SF-36 scales but high ceiling effects, especially in the social functioning, role physical and role emotional scales. However, in the current study, effect sizes were similar between scales that had lower ceiling effects vs
these three scales, suggesting that high ceiling effects did not have an impact on responsiveness to change.
Our study has several strengths. First, this is the first study that evaluates responsiveness to change of SF-36 in a real-life cohort. Secondly, this study comprehensively assesses SF-36 in a cohort outside USA. Although another study from Mexico assessed SF-36, they did not provide detailed information on SF-36 scores [24
]. Thirdly, our cohort comprehensively collected clinical, radiological and laboratory data and treated patients with ULT to a goal of <6.0
mg/dl. Finally, the seven patients who were on prophylaxis with colchicine alone showed improvement in their HRQOL. These trends are interesting and thought provoking, but should be considered preliminary.
Our study is not without limitations. First, this is a single academic centre-based study, which limits the generalizability as most gout is treated in primary care. Also, our data need to be replicated in larger cohorts. Secondly, we did not evaluate other HRQOL measures such as HAQ-disability index that are responsive to change in gout [4
]. Thirdly, we did not include a placebo group; the improvement in HRQOL measures may need to be validated in a placebo-controlled study. Finally, our MCID cut-off for the SF-36 is based on the data from studies in RA and scleroderma [17
]. There are no MCID values currently available in gout.
To conclude, in this real-life observational cohort, long-term treatment with ULT or colchicine was associated with statistical and clinically meaningful improvements in the number of flares and HRQOL at 1 year, and was maintained at 2 years. SF-36, especially physical domains and PCS, are responsive to change with treatment in gout over time.