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Rheumatology 2002; 41: 793-800
© 2002 British Society for Rheumatology
Original Papers |
The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century
ARC Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT and
1 Norfolk Arthritis Register, Norfolk and Norwich University Hospital, Norfolk NR4 7UZ, UK
| Abstract |
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Background. It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) for the UK were published. Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA, especially in women.
Objectives. To estimate the age- and sex-specific point prevalence of RA (defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment). The estimate was made in the primary care setting in Norfolk, UK.
Methods. A stratified random sample was drawn from seven age and gender bands. The 7050 individuals selected were mailed a screening questionnaire. Positive responders were invited to attend for a clinical examination. The sample was matched against the names in the Norfolk Arthritis Register (NOAR), a register of incident cases of inflammatory polyarthritis which has been in existence since 1990.
Results. The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission. In addition, some cases who failed to attend for examination had significant disability. These prevalence figures are therefore an underestimate.
Conclusions. The prevalence of RA in women, but not in men, in the UK may have fallen since the 1950s.
| Introduction |
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It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) in the UK were published [1]. Since that time, a new set of classification criteria has been introduced [2]. In addition, there is some evidence that there has been a decline in the incidence and prevalence of RA both in the UK [35] and elsewhere [69]. Data from the third and fourth national morbidity surveys in the UK [10, 11] show a decrease in the prevalence of RA and allied conditions (which includes ankylosing spondylitis) between 1981 and 1991. These national morbidity surveys are based on visits to a general practitioner (GP) during a 1-yr period for a GP diagnosis of RA or a related condition. During this period, the overall prevalence of RA appears to have fallen by 31% in women and 19% in men (although the methods used in the two surveys were not exactly the same) (Fig. 1
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This prevalence study was conducted in the area in which the Norfolk Arthritis Register (NOAR) is set. NOAR is a primary-care-based inception cohort of adults with inflammatory polyarthritis (of which RA is a subset) with onset since 1990 [12]. The study reported in this paper presents a number of additional opportunities for understanding the occurrence of RA. First, it offers the opportunity to establish the proportion of previously identified incident cases of RA that is identifiable in a subsequent cross-sectional prevalence study. This will provide valuable information on remission ratesinformation which is essential for modelling the burden of disease. Secondly, it offers an opportunity to assess the completeness of notification to NOAR (by identifying cases of RA which should have been known to NOAR) and adjusting our incidence estimates accordingly. It also offers a further chance to evaluate the 1987 ACR classification criteria for RA [2] in a population.
It is generally believed that the occurrence of RA does not vary amongst people of Northern European origin (whether living in Europe or North America) [13]. However, there is evidence within the UK that the prognosis of RA may be influenced by social deprivation. [14, 15]. We therefore explored the effect of area of residence on the estimated prevalence (which is influenced by disease duration as well as incidence) of RA within Norfolk.
| Methods |
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We conducted a two-stage population-based survey. The first stage was a screening questionnaire and the second stage included a clinical examination of positive responders to the screening questionnaire. The study was approved by the Norwich Local Research Ethics Committee.
Sampling
Eleven computerized general practices (GenP) reflecting urban, rural and coastal populations within the former Norwich Health Authority participated in the study. The total population covered by these practices was approximately 60 000. According to National Census data, <1% of the population of Norfolk belong to ethnic minorities.
The registers of adult patients from each GenP were divided into four age bands (1644, 4564, 6574 and 75+ yr) for each gender. Data from NOAR show that the incidence of RA in men aged 1644 yr is very low [2.9 per 100 000; 95% confidence interval (CI) 0.8, 7.6] [12]. Therefore, men aged 1644 yr were not included in the study because of the large sample size that would have been required to provide robust estimates of the prevalence of RA in this group. The sample size of each of the remaining seven agesex bands (Table 1
) was based on being able to show that a prevalence of RA outside the range of 0.52.0 times that reported by Lawrence [1] was significantly different from Lawrence's data, and allowed for a 25% non-response rate. The sample size drawn from each practice was weighted according to the size of the practice. Within each GenP, the subjects in each of the seven agesex bands were sorted by date of birth. We then selected every nth subject, where n is the number of people in that agesex band divided by the sample size in that agesex band required from that GenP. GPs were shown the list of selected subjects and could request that individuals should be excluded if they felt, for example, that the survey would cause severe psychological distress or the individual was terminally ill. Subjects excluded in this way were replaced by the next person on the list (sorted by date of birth).
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The Townsend score
The Townsend score is a composite index of material deprivation based on the following four variables from the 1991 National Census: percentage of unemployed males; percentage of households which do not own a car; percentage of households which are not owner-occupied; and percentage of overcrowded households [16]. The enumeration district is the smallest geographical unit to which Townsend scores can be assigned and has a few hundred residents. Townsend scores for the whole of England and Wales have been divided into quintiles. Each subject in this prevalence study was assigned to one of these quintiles on the basis of the Townsend score of his/her enumeration district (determined from the postcode).
Screening
The GenPs were studied sequentially. The selected subjects from each GenP were sent a validated screening questionnaire [17], a covering letter signed by their GP, and a prepaid envelope. The screening questionnaire included questions on demography, joint complaints and the British version of the Stanford Health Assessment Questionnaire (HAQ) [18, 19]. Two weeks after the date of the first mailing, non-responders were sent a reminder postcard. Two weeks after the second mailing the remaining non-responders were sent a second letter, a screening questionnaire and a prepaid envelope.
Positive responders were individuals who reported ever having swelling of two or more joints (excluding the ankles) lasting for 4 or more weeks, or who had ever been told by a doctor that they had RA. They were invited to attend a clinic at the GenP surgery for examination by a research nurse. Subjects who were unable to attend the clinic were offered a home visit. The research nurse interviewed the subject and completed a second, more detailed questionnaire. The subject's joints were examined for tenderness, soft tissue swelling and deformity. A joint was said to be deformed if the subject could not adopt the anatomical position or had lost one-third or more of the normal range of movements. Subjects were also examined for subcutaneous nodules. On the basis of this examination, a modified version of the 1987 ACR criteria was applied (Table 2
). A similar modification [20], which required access to the patient's records, had been validated. This modification (Table 2
) was made for use in a population survey without access to patient records. It was validated against a rheumatologist's diagnosis based on the study documentation. Those who satisfied two or more of the modified ACR criteria were asked to give a blood sample for rheumatoid factor analysis (unless there was documented evidence of previous seropositivity from our laboratory) and to have X-rays of the hands and feet (unless X-rays taken within the last 2 yr were available). The questionnaires, blood samples and X-rays were returned to Manchester for data entry and analysis. X-rays were read for erosions by two observers using Larsen's method [21]. A score of two or more in any joint indicated that the subject had erosions. A third observer arbitrated if there was disagreement about the presence of erosions.
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In addition, 251 individuals who were negative responders were invited to attend for clinical assessment. They were selected at random with the aim of examining approximately 21 from each GenP (three from each agesex band).
Statistics
Prevalence in each stratum was calculated by dividing the number of cases of RA by the true size of the stratum sample (the number of questionnaires mailed out minus the number of individuals found to have died or moved away). The 95% confidence intervals (CI) were based on the Poisson distribution of the number of cases. The association between material deprivation (Townsend score) and response was assessed using the svylogit (i.e. logistic regression for survey data) command in STATA version 6.0 [22]. This method of analysis takes account of between-stratum differences in the sampling fraction by using probability weights.
| Results |
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Age- and sex-specific prevalence of RA
On average, each GenP asked for 20 individuals to be excluded and replaced. Half of the substitutions were because the individual was known to have died. Most of the remaining substitutions were due to dementia, severe mental illness or terminal illness. Questionnaires were then mailed to 7050 people (Fig. 2
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The 1025 positive responders were invited to attend for a clinical assessment and 818 (80%) agreed. Sixty-six subjects satisfied at least four of the seven ACR criteria when applied as listed in Table 2
The 1987 ACR criteria for RA do not have any exclusions. Four individuals who satisfied the ACR criteria in this survey were known to have other inflammatory conditions which may have accounted for the findings: one case each of scleroderma, Wegener's granulomatosis, ankylosing spondylitis and juvenile-onset chronic arthritis. In addition, many people in the older age groups had been given a clinical diagnosis of osteoarthritis. None of these people was excluded from our analysis. In addition to the modified ACR criteria in list format (Table 2
) we also applied the ACR criteria in their original list and classification tree format [2]. Substantially fewer cases were identified using the list (4/7 criteria) format and somewhat fewer by the classification tree format (Table 4
).
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Sensitivity analysis
We used the number of questionnaires mailed minus the number of people assumed to have died or moved away as the true denominator in our prevalence estimates. In effect, this method assumes that none of the non-responders to the screening questionnaire or to the examination phase had RA. These estimates, therefore, give the minimum RA prevalence in the population surveyed (Table 1
). A number of other assumptions could have been used. For example, we could have assumed that all the non-responders had RA (which would have given a maximum prevalence), but this seems intrinsically extremely unlikely. A more plausible assumption is that the proportion who had RA was the same among non-responders as among responders to the screening questionnaire. If this was the case, one would expect the same prevalence of RA amongst those who responded to the second and third mailings (who would have been labelled as non-responders if the reminders had not been sent) as in those who responded to the first mailing. In fact the proportion with RA fell progressively with each mailing: the odds ratio (OR) of screening positive in the second vs the first mailing was 0.79 (95% CI 0.67, 0.95) and the OR of screening positive in the third vs the first mailing was 0.52 (95% CI 0.43, 0.63). This favours the assumption that all remaining non-responders did not have RA (although it is likely that some cases remain undetected this way). Alternatively, we may assume that non-responders to the screening questionnaire did not have RA, but that those who declined examination had the same prevalence of RA as those who were examined (Table 1
). One way to look at this would be to compare the HAQ scores from the screening questionnaire for those positive responders who agreed to an examination and those who did not agree. If the prevalence of RA were the same in those who declined examination as in those who agreed, one would expect the HAQ scores in the two groups to be similar. In fact, those who were examined had higher HAQ scores than those who declined examination. Sixty-two per cent of those who were examined and 49% of those who declined examination had an HAQ score >0. Those who had an HAQ score between 0.1 and 2.0 were significantly more likely to agree to an examination than those with an HAQ score of 0, whereas those with an HAQ score >2.0 were equally likely to attend as those with an HAQ score of 0 (Table 5
). Again, this favours the assumption that those who were not examined did not have RA (although some very disabled cases of RA will have been missed).
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Negative responders
Two hundred and twelve (84%) of the negative responders who were invited for examination agreed to attend (median number from each practice=20, range 1630). They included 120 women and the median age was 67.5 yr (range 2094 yr). None of these people satisfied the ACR criteria. Thus, the screening questionnaire had 100% sensitivity in detecting RA, with a lower 95% CI of 98.3% based on a binomial distribution.
RA in remission
The names selected for inclusion in this prevalence survey were matched against the register of people who had ever been notified to NOAR. Patients are notified to NOAR from primary or secondary care if they have soft tissue swelling of two or more joints lasting for 4 or more weeks with an onset since 1 January 1990 [12]. Twenty-four matches were found, 13 of whom had ever satisfied the 1987 ACR criteria (as part of the NOAR assessments) when applied cumulatively (i.e. if a single criterion was satisfied it was carried forward as positive to all subsequent assessments). All 13 were positive responders. However, only five of the 11 patients who attended for an examination satisfied the ACR criteria at the time of the assessment. All of the remaining six were in remission on treatment, with few or no joint abnormalities on examination. There were no cases who had previously satisfied the ACR criteria (as part of the NOAR assessments) who had gone into spontaneous remission.
| Discussion |
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These are the first age- and sex-specific estimates of the prevalence of RA in the UK since the seminal paper by Lawrence published 40 yr ago [1]. Lawrence combined the results of two population surveys conducted in Leigh, Lancashire (an urban area) and Wensleydale, Yorkshire (a rural area). The total sample size was 2590 adults and 2234 (86%) were examined. He found 24 cases who satisfied the recently published 1958 ARA criteria for definite RA [23]. He took as the denominator those individuals who attended for an examination (thus assuming the same rate of RA in those who were and those who were not examined) (Table 6
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Our findings are compatible with a number of previous studies that have shown a fall in the incidence of RA in women since the 1960s [4, 24]. This fall has been attributed to a protective effect of the oral contraceptive pill (OCP) [25] or some other factor related to the use of the OCP. A NOAR casecontrol study of incident RA also showed this protective effect [26]. It is possible that use of the OCP reached saturation levels in the late 1980s and that is why the prevalence of RA in women has now stabilized. Women currently aged over 75 yr are too old to have taken the OCP and this may be why the prevalence of RA has not changed in this age group.
There have only been a few studies of the prevalence of RA in mainland Europe since the introduction of the 1987 ACR criteria. All report a lower prevalence than identified in the present study. In 1994 the prevalence of RA in Oslo, based on a register of attendance at a hospital rheumatology clinic and satisfying the 1987 ACR criteria, was 0.67% for women and 0.19% for men aged 2079 yr [27]. A Swedish study based on a two-stage population screening survey similar to that used in our study (but confined to adults aged 2075 yr) estimated a total population prevalence for this age group of 0.51% [28]. A two-stage population screening survey in Brittany (the first phase being conducted by telephone) found a prevalence of 0.74% in women and 0.26% in men [29]. RA appears to be less frequent in southern than northern Europe. Rates reported from north-west Greece are 0.45% for women and 0.19% for men (aged 16+ yr) [30], those in northern Italy are 0.51% for women and 0.13% for men [31], and those in Yugoslavia are 0.29% for women and 0.09% for men [32]. Some of these differences may be explained by study design or by different agesex structures of local populations.
On the other hand, our figures are somewhat lower than the most recent estimates from Rochester, Minnesota [8] (1.40% for women and 0.74% for men). These US estimates were based on individuals who had attended for medical care and who had ever satisfied the ACR criteria prior to the prevalence date (31 December 1985). Thus, these US results provide an estimate of cumulative prevalence, whereas our estimates provide a point prevalence of people with clinical and/or radiological evidence of current or past RA. The inclusion of joint deformity in our interpretation of the ACR criteria (Table 2
) enabled us to capture individuals who were in remission but had some accumulated damage from their RA [20]. However, we will have missed individuals who were in spontaneous or treatment-induced remission and had no sequelae of previous disease activity. Matching our prevalence study against the NOAR register showed that six out of 13 patients who had previously satisfied the ACR criteria (as part of the NOAR assessments) were on disease-modifying treatment and failed to satisfy the criteria on the day of the prevalence survey, but none had entered spontaneous remission. All subjects in NOAR have less than a 10-yr history of arthritis. In order to adjust the prevalence estimates for cases of RA which are in remission, we also need to know what proportion of RA cases of more than 10 yr duration might have been missed. The proportion is likely to be lower in this group due to cumulative joint deformity and less effective treatment strategies in the past. Amongst the 735 subjects assessed who failed to satisfy the ACR criteria on the day of the examination and who were not on NOAR, a further eight subjects were on a disease-modifying drug (methotrexate, sulphasalazine, an antimalarial or azathioprine). One had lupus and another ankylosing spondylitis, but the remaining six had a consultant diagnosis of RA or undifferentiated inflammatory polyarthritis. It is likely that some of these individuals would have satisfied the ACR criteria at some point in the past. We were not, therefore, able to adjust accurately our estimates of RA prevalence for cases missed due to treatment-induced remission. Nevertheless, it is important to consider these individuals in any RA prevalence estimates that are being used for health service planning, as these people represent a cost to the health service. We did not include them in the present study as they did not satisfy our criteria for a prevalent case and, while these excluded individuals were a cost to the health service, some of the subjects who were included in our estimates had never sought medical help for their arthritis. With improving treatment of RA, it is likely that there will be an increasing number of people who have previously been diagnosed as having RA but, as a result of successful treatment, have no evidence of the disease on a prevalence date.
In conclusion, we believe that these estimates are robust and generalizable, and provide the best currently available figures on the burden of RA in the UK population.
| Acknowledgments |
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We are grateful to Lynn Massingham and Teresa Kempson for their work in examining the subjects and co-ordinating the project. We thank Drs Marwan Bukhari and Beverley Harrison for their assistance in reading the X-rays. We thank the GP practices for access to their patient lists and the use of their premises for clinics. The study was funded from the core support by the Arthritis Research Campaign, UK, to the ARC Epidemiology Unit.
| Notes |
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Correspondence to: D. Symmons.
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