Introduction Many doctors believe that patients with gout are unwilling to receive urate-lowering therapy (ULT) and blame them for poor adherence to management.
Objective To test the effectiveness of a complex intervention for gout that incorporates key elements of current guidelines, including full patient information, delivered in an optimal setting (specialist hospital clinic).
Method Observational study of patients reporting ongoing attacks of gout recruited from primary care lists. 106 participants (94 men, 12 women; mean age 61 years) were enrolled in the study. Patients received a predominantly nurse-delivered intervention that included education, individualised lifestyle advice and appropriate ULT. The predefined goal was to achieve serum uric acid (SUA) levels ≤360 μmol/l after 1 year in at least 70% of participants.
Results Of the 106 participants at baseline, 16% had tophi; mean (SD) baseline SUA was 456 (98) µmol/l. All participants agreed to joint aspiration to confirm gout and all wished to receive ULT. At 12 months, 92% of the 106 participants had achieved the therapeutic target (SUA≤360 µmol); 85% had SUA <300 µmol/l. Allopurinol was the most commonly used ULT, requiring a median dose of 400 mg daily to achieve the target. Improvements in Short Form-36 were observed (significant for pain) after 1 year.
Conclusion A predominantly nurse-led intervention including education, lifestyle advice and ULT can successfully achieve the recommended treatment target in more than 9 out of 10 patients. Full explanation and discussion about the nature of gout and its treatment options and individualisation of management probably account for this success.
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Gout is a crystal deposition disease that affects 1–2% of UK adults, increasing in prevalence with age to affect 7% of men aged >65 and 3% of women aged >85.1 It is the most common inflammatory arthritis in men and the most common inflammatory arthritis in older women.1,–,3 Unlike other common forms of arthritis we have a good understanding of gout pathogenesis and have effective treatments to eliminate the causative agent (urate crystals) and ‘cure’ the disease.4
Unfortunately, audit shows that the management of patients with gout is far from optimal.5,–,7 Three UK studies5 ,7 ,8 suggest that only one-third to one-half of patients with gout receive urate lowering therapy (ULT) and that even when given, ULT is often prescribed at a single fixed dose (usually allopurinol 300 mg daily) that is insufficient for many patients.7 Furthermore, few patients receive a clear explanation of their gout or appropriate lifestyle advice to reduce predisposing risk factors.7 As a consequence, only a minority become free from gout, the majority continuing to experience acute attacks and to be at risk of progression of their disease and of developing secondary irreversible joint damage.3 There are many barriers to care of gout7 ,9 but the commonly documented poor adherence to ULT is often blamed more on patients than a lack of appropriate information from their doctor.10 ,11
Both the British Society for Rheumatology and European League Against Rheumatism have published evidence-based recommendations for management of gout.12 ,13 However, these are based largely on expert consensus, supported by relatively limited research evidence that mainly focuses on short-term studies of individual treatments. To our knowledge there are no long-term trials investigating the benefits of a complex intervention or ‘package of care’ that reflects recommended best practice. Notwithstanding the absence of randomised controlled trial evidence, there is strong consensus on the components of management that will eliminate urate crystals and effect a ‘cure’.14 Specifically, this is to combine patient education and individualised lifestyle advice with appropriate use of ULTs to achieve and sustain a target serum uric acid (SUA) level of <360–300 μmol/l.9 ,11 ,13
Because of the high prevalence of gout and ready availability of effective treatment the vast majority of patients with gout are managed in primary care. Nurse delivery of care that reflects recommended best practice is a model that has been applied successfully to management of other common chronic conditions such as asthma15 and diabetes.16 Therefore the aim of this study was to test the effectiveness of a package of care for patients with gout that (1) incorporates the key elements of current recommended ‘best practice’12 ,13; (2) is predominantly delivered by a nurse; (3) is delivered in the optimal setting of an expert, hospital-based gout clinic. Should this ‘proof-of-concept’ study be successful, the package of care would next be tested in a general practice setting (funded, as for this proof-of-concept study, by Arthritis Research UK).
Approval for the study was obtained from the National Health Service (NHS) Nottingham County research ethics committee.
Participants were recruited from 25 general practices in Nottinghamshire. Patients with a diagnosis of gout on the general practice registers were eligible if they were aged between 30 and 100, had a definite diagnosis of gout17 and reported at least one acute gout attack within the previous year, irrespective of any ULT. Potentially eligible participants were first identified through a postal questionnaire to patients with gout on the practice registers. Respondents reporting attacks within the past 12 months were telephoned for a brief discussion to confirm likely eligibility, and then sent full written information about the study and invited for clinical assessment in Academic Rheumatology, City Hospital, where fully informed written consent was obtained. The recruitment period ran from March to July 2010.
At their first visit each participant received a full clinical assessment (enquiry and examination) from a rheumatologist specialising in crystal-associated arthritis (MD). The site and size of any subcutaneous tophi was noted. All participants were offered aspiration preferentially of an intercritical joint (mainly first metatarsophalangeal joint or knee), or a tophus, but a minority preferred aspiration of a previously unaffected knee to an intercritical small joint, to confirm definite ‘crystal-proven’ gout.17 Synovial fluid crystal identification was undertaken in Academic Rheumatology (by MD) and the participant informed of the result within 10 min of aspiration.
Participants with definite gout17 were given detailed information and education about (1) the cause of the disease; (2) its recognised risk factors; (3) clinical consequences with respect to ongoing acute attacks and possible irreversible joint damage; (4) strategies, including discussion of individualised modifiable risk factors (such as weight loss if obese) and ULT, to sufficiently reduce SUA levels below the critical ‘saturation point’ of 360 µmol/l to prevent new crystal formation and to dissolve existing crystals (ie, to effect a ‘cure’). Illness perceptions about the causes of their gout, its effect on their life, the likely outcome of their gout and available treatment options were fully discussed and an individualised management plan was agreed. An Arthritis Research UK information leaflet18 on gout was also given to all participants. Cardiovascular risks from hyperuricaemia were only dealt with in those patients who specifically enquired, since this remains a controversial topic and is not an indication for ULT. The initial interview, assessment, discussion and agreement of a management plan with the doctor took approximately 1 h, twice that of a routine NHS new patient appointment, but did include joint aspiration and crystal analysis. Blood was taken for measurement of baseline SUA and renal function by a specialist gout nurse (WJ), who also reinforced the management plan, gave the participant the written information and booked the follow-up visit (approximately 20 min). Other blood tests and joint radiographs were performed only if clinically indicated.
Participants were subsequently followed up by the specialist nurse by telephone or in person to monitor clinical progress and success of lifestyle modification, to titrate up ULT according to SUA levels, to adjust the management plan and to deal with concerns as they arose. The frequency of nurse appointments and repeat blood tests was determined by individual needs, although SUA measuring and upward titration of ULT was approximately monthly until the therapeutic target was reached, then SUA was measured every 3 months. The nurse-led the management but could consult the rheumatologist to discuss certain clinical decisions (eg, change from one ULT to another). Follow-up was for 1 year. The final nurse-led visit lasted approximately 20 min.
The primary outcome was the percentage of patients who had their SUA reduced below 360 µmol/l at 12 months—success was defined empirically as 70% achieving this therapeutic target at 12 months. Other outcomes were the percentage achieving a SUA of <300 µmol/l at 12 months; frequency of acute attacks; number and size of tophi; and the Short Form-36 (SF-36) quality-of-life measure (performed at baseline and 12 months).
Descriptive statistics were used to determine the percentage of patients in whom the therapeutic target was achieved. This was analysed on an intention-to-treat (ITT) basis (last value carried forward). Change in SF-36 was analysed with a Student t test, pairing questionnaires at baseline and final visit in study completers, using SPSS version 14.0.
Participant characteristics and adherence
The response rate to the questionnaire was 55%. Twenty-five responders were considered ineligible or declined involvement at the telephone interview but 116 were considered potentially eligible and attended Academic Rheumatology. Of these, 106 participants met the eligibility criteria (eight had calcium pyrophosphate crystal deposition and two had uncomplicated osteoarthritis) and proceeded to the study. Table 1 illustrates the baseline characteristics of the study participants.
At their initial visit, after a full explanation of gout, all participants consented to intercritical aspiration of a joint to confirm gout and all wished to receive ULT. Adherence to treatment was good with 96 participants (91%) completing the 12-month follow-up. Reasons for non-completion were death due to non-treatment-related causes (two patients); withdrawal due to personal time constraints (one); withdrawal due to side effects of ULT (three); lost to follow-up (three); and one participant on the renal transplantation list was advised not to start ULT but to await review after he had received his transplant (which occurred after study completion). Side effects experienced were diarrhoea, headaches and dizziness with benzbromarone and a rash and gastrointestinal upset with allopurinol.
At the final visit (ITT) 80 participants receiving ULT (79%) were taking allopurinol (median dose 400 mg daily; range 100–700 mg; 100 mg (one patient), 200 mg (six), 300 mg (22), 400 mg (20), 500 mg (20), 600 mg (nine), 700 mg (two)); 16 (16%) were taking febuxostat (80 mg (11), 120 mg (five)); and five (5%) were taking benzbromarone (50 mg (two), 100 mg (three)). Reasons for switching from allopurinol to second-line ULT were treatment failure (eight), side effects (11) or concomitant drug interaction (two).
At study end the percentage of participants with a SUA <360 μmol/l was 92% (ITT analysis). This was considerably greater than the predefined target of 70%. Eighty-five per cent of participants had a SUA <300 µmol/l at 12 months.
Participants had a mean of eight SUA measurements during the observation period. The mean SUA reduced from baseline to 268 µmol/l (table 2). In the 17 patients with tophi at baseline almost one-third had a reduction in number or size at final visit.
In study completers, the mean number of self-reported attacks/year reduced to 2.4 (SD 2.3). Table 3 shows the decline in the number of attacks and the number of participants experiencing attacks with time.
After full discussion, only four participants (4%) opted for prophylaxis (colchicine 0.5 mg twice daily) during upward titration of ULT. These four participants had a mean of nine attacks during the follow-up period (SD 2.9). This is compared with a mean of 2.4 (SD 2.3) attacks for the whole group. Comparison of SF-36 scores in study completers shows that there was a statistically significant improvement in the bodily pain domain (p=0.016).
This study shows that with a ‘package of care’ that includes patient education, individualised lifestyle advice and slow upward titration of ULT according to serial SUA levels (ie, recommended best practice),12 ,13 more than 90% of participants achieved the therapeutic target of a SUA <360 µmol/l, with 85% achieving a SUA<300 µmol/l. After a full explanation about the cause of gout, its risk factors and prognosis (including the risk of chronic joint damage), and available treatment strategies that can eliminate the crystals, all participants wished to receive ULT. There was good adherence to treatment, with more than 90% of participants completing the 12-month observation period. Given optimal circumstances (patient education, patients knowing their therapeutic target and regular contact with a nurse specialist), the recommended complex intervention is effective in more than nine out of 10 people with gout.
There are no previous studies of complex interventions in gout. However, there are studies that show poor adherence to ULT10 ,11 ,19—indeed, adherence to ULT for gout is possibly the worst of any medication for chronic disease.11 ,19 The need for patient and professional education to enable ‘cure’ in gout has been highlighted previously.20 However, despite international guidelines published in 2006,13 significant barriers to effective gout management remain.21 ,22 A recent study in this department found that the main barriers to treatment were a lack of understanding of both the aetiology and management of gout in men and women with gout but also in health professionals.21 Many people focus mainly on acute attacks and have no concept of ongoing, potentially damaging crystal deposition that may lead to tophi and irreversible joint damage.21 When ULT is offered, it is often given as a single efficient dose, which commonly provokes acute attacks and, without a clear explanation, patients often stop the ULT and are disinclined to restart it.21 However, as in this study, if ULT is titrated slowly and the risk of flare is explained to patients they then understand the need to continue their medication despite flaring and the need for long-term treatment to maintain cure. This suggests that education of both patients and health professionals is of paramount importance if both recommended best practice and good adherence are to be achieved. With full explanation, dealing with illness perceptions and barriers to treatment, adherence can be achieved that is even higher than that for other chronic diseases.23 Of interest, every patient in this study accepted an intercritical joint aspirate to confirm with 100% confidence whether they had gout. This is much higher than many people would have predicted, but again reflects the importance of a full explanation in determining patient decision-making.
Most patients were taking allopurinol at study completion, confirming that this is a well-tolerated and effective ULT to be considered first for patients with gout.12 ,13 ,24 However, the median dose of allopurinol required to achieve the therapeutic target was 400 mg. This is in accord with a previous community study in Nottingham,7 which found that many patients who receive the commonly prescribed single dose of 300 mg dose are undertreated and continue to have acute attacks and progression of their disease. This reinforces the requirement to individualise the dose of ULT by titration against the SUA until the therapeutic target has been achieved.12 ,13 This, in conjunction with full explanation, also accounts for the high success rate in achieving the therapeutic target, in contrast to recent large randomised control trials that report low success rates when using a fixed-dose regimen of allopurinol 300 mg daily.25 ,26 The majority of patients who had a contraindication or side effects with allopurinol were successfully treated with a second or third ULT, with only three participants leaving the study having experienced self-limiting but troublesome side effects from ULT and being unwilling to try alternative options.
After full discussion most patients expressed a preference for no prophylaxis during ULT dose escalation, especially with the slow titration that is possible with allopurinol. Interestingly, despite this, the mean number of attacks during the 12-month observation period was less than that reported in the previous year. This suggests that unlike initiation with 300 mg allopurinol or 80 mg febuxostat (both very efficient urate-lowering doses which usually provoke acute attacks and therefore justify consideration of prophylaxis),12 ,13 a regimen with a low starting dose of ULT (eg, 100 mg allopurinol or 50 mg benzbromarone) and subsequent monthly upward titration may not cause more attacks than the patient might otherwise have experienced. Therefore, the use of a second drug (colchicine or a non-steroidal anti-inflammatory drug) with its own potential for side effects may not be required for this indication. The caveat to this may be those patients with greater SUA or tophi at baseline, who are likely to have a higher burden of crystals so are more likely to have a flare when their uric acid level is reduced. However, further specific study comparing these two options is required.
A statistically significant change in the pain domain of the SF-36 shows that with effective treatment of gout a patient's quality of life can improve. This agrees with one previous study27 that found a statistically significant improvement in six of the SF-36 domains after 12 months of ULT, with the largest improvement in the bodily pain domain. However, they excluded patients who had had a gout flare in the 4 weeks before completing the questionnaire, which may explain the increased number of significantly improved domains.
There are several caveats to this study. First, although the response rate to the questionnaire was reasonable, not all patients with gout accepted the invitation to take part in the study so there may have been selection bias towards those patients who were more interested in receiving treatment. Second, the duration of the study was only 12 months, which is too short a period to expect complete elimination of urate crystals from all participants and to demonstrate ‘cure’. Nevertheless, the mean frequency of attacks was less during the study period than in the previous year and the size and number of tophi in those with subcutaneous deposits was diminishing, suggesting that given longer follow-up all participants with effectively lowered SUA would reach the state of ‘cure’. Third, this was a hospital-based study in which participants were fully assessed by a gout expert within a longer than average initial appointment. Such contextual aspects will have influenced patient expectancy and outcomes, and may limit the generalisability of the findings. However, the year-long follow-up was carried out by a nurse, and nurse-led management of other chronic conditions has been successfully transferred into primary care.15 ,16 Given the excellent outcome such a predominantly nurse-led service could prove cost-effective for the NHS. However, further work would need to ascertain whether a nurse-lead community approach could be successful for gout management, and this is the subject of a recently funded forthcoming randomised controlled trial.
In conclusion, this proof-of-concept study has shown that a predominantly nurse-led complex intervention that includes key elements of recommended best practice is successful in achieving the therapeutic target and maintaining high adherence to ULT over a 12-month period in more than nine out of 10 people with clinically evident gout. Further study is required to determine whether a similar nurse-led intervention can be delivered successfully over a longer period in primary care and result in a higher rate of ‘cure’ than is currently seen in people with gout.
The authors are indebted to Arthritis Research UK who funded this work (Award reference 18827) and to the patients who participated in the study. Arthritis Research UK did not participate in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Funding Arthritis Research UK.
Competing interests (1) FR, WJ, MD have no support from companies for the submitted work; (2) MD has received consultancy or speaker fees from Ardea Biosciences, Ipsen, Menarini, Novartis and Savient within the past 3 years (3) FR, WJ and MD's spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) FR, WJ, MD have no non-financial interests that may be relevant to the submitted work.
Ethics approval NHS Nottingham County research ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.