Orthopaedic intervention in early rheumatoid arthritis. Occurrence and predictive factors in an inception cohort of 1064 patients followed for 5 years

D. James, A. Young1, E. Kulinskaya2, E. Knight2, W. Thompson3, W. Ollier4 and J. Dixey4 on behalf of the Early Rheumatoid Arthritis Study Group (ERAS), UK

Diana Princess of Wales Hospital, Grimsby, UK, 1ERAS, Rheumatology Unit, City Hospital, St. Albans, Herts AL3 5PN, UK, 2Department of Statistics, HRDSU, University of Hertfordshire, UK, 3Department of Genotyping, ARC ERU, University of Manchester, Manchester, UK and 4RJAH Orthopaedic Hospital, Oswestry, UK.

Correspondence to: A. Young, ERAS, Rheumatology Unit, City Hospital, St Albans, Herts AL3 5PN, UK. E-mail: eras{at}whht.nhs.uk


    Abstract
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
Objectives. To assess the occurrence of and predictive factors for orthopaedic surgery in an inception cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 5 yr in nine regions in England.

Methods. Standard clinical, laboratory and radiological assessments and all interventions were recorded at baseline and yearly in RA patients (less than 2 yrs symptoms) prior to the use of disease-modifying drugs.

Results. One thousand and sixty-four patients completed 5 yr of follow-up. Two hundred and sixty-four orthopaedic procedures for RA were performed in 181 (17%) patients at a median of 36.5 months from baseline. Seventy-five (7%) had replacements of major joints. Risk factors at baseline for large joint replacement surgery were a low haemoglobin concentration [odds ratio scores (OR) 3.4, 95% confidence interval (CI) 2.1–5.8] and high scores for erythrocyte sedimentation rate (ESR) (OR 3.2, CI 1.8–5.3), disease activity (DAS) (OR 2.1, CI 1.2–3.5) and Larsen X-rays (OR 2.6, CI 1.4–4.8). For hand or foot joint surgery (4%), risk factors included female gender (OR 3.2, CI 1.3–7.6), joint score (OR 2.3, CI 1.2–4.3), erosions (OR 2.3, CI 1.1–4.8), DAS (OR 2.4, 1.3–4.5) and Health Assessment Questionnaire score (OR 1.9, CI 1.0–3.6). No significant associations were seen for tendon, soft tissue or other minor procedures (6%). The HLA-DRB1 RA shared epitope was associated with any type of orthopaedic surgery (OR 1.7, CI 1.1–2.7).

Conclusions. Eleven per cent of RA patients treated with conventional drug therapy for 5 yr underwent large- or small-joint surgery, an outcome which could be compared against that for new disease-modifying drugs. Risk factors varied according to type of surgery, but included standard clinical and laboratory measures. In order to reduce the eventual need for surgery, a therapeutic target in the first year of RA is the suppression of disease activity, as measured by haemoglobin and ESR. These are useful details for clinicians, health professionals and patients.

KEY WORDS: Rheumatoid arthritis, Orthopaedic surgery, RA outcomes, Prognostic factors.


    Introduction
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
The course of RA varies greatly from mild, even self-limiting disease to a severe destructive variant progressing rapidly over a few years, a form which has been described mainly in terms of radiographic damage. Despite early and more aggressive treatment policies, progressive destruction of joints continues in a subgroup of RA patients who eventually require joint surgery. Such outcomes have been reported mainly from observational studies in Finland [1], Holland [2], the USA [3] and western Scotland [4], but from only few genuine inception cohorts, as in Sweden [5]. Despite the importance of RA, the proportion of patients who undergo orthopaedic surgery and the rates of joint replacements for RA in the UK are not known. Epidemiological analysis in the UK has been limited by incomplete and inaccurate coding for the underlying primary and secondary diagnoses [6, 7]. Exact figures for the requirement, timing and type of orthopaedic surgery for RA are needed to inform patients and rheumatologists and for the planning of future health-care services.

When orthopaedic surgery, particularly large joint replacement, is needed as part of the management of RA in the course of the disease, it may be an indicator of failure of medical therapy and poor prognosis. Surgical outcomes could be used to compare conventional drug regimens with newer and future therapies, and in particular the recent availability of tumour necrosis factor {alpha}-blocking drugs for RA. These agents have improved short-term efficacy [8, 9] but at considerable cost, which has highlighted the need for information both on the proportion of RA patients who fail conventional drug therapy and require surgery, and on when this occurs in the course of RA. Few predictive tests of long-term outcome in RA are available, although recently both a high erythrocyte sedimentation rate (ESR) and the HLA-DRB1 RA shared epitope (SE) have been reported as clinically useful prognostic markers for major joint replacement [4].

Observational studies are still required in order to assess long-term outcomes and prognostic factors, and large numbers are needed for the less common outcomes, such as orthopaedic surgery. If well conducted, such studies offer alternative and acceptable levels of evidence [10]. This paper reports the frequency and type of, and predictive markers for, orthopaedic interventions in RA patients observed for 5 yr from presentation in nine regions in England.


    Patients, materials and methods
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
The entry criteria and follow-up details have been described in previous reports from this group [11, 12]. Consecutive patients with RA were recruited from rheumatology out-patient clinics in nine districts of England if symptoms of RA had lasted less than 2 yr and second-line drug medication had not been used. Patients who did not fulfil the 1987 revised American College of Rheumatology (ACR) criteria for RA [13] continued to be followed and subjected to subgroup analysis. Only patients who completed 5 yr of follow-up were included in the present analysis. Details of differences between centres have been reported previously [12].

Trained metrologists performed standard clinical and laboratory assessments at baseline and at yearly intervals. These included two articular indices, one based mainly on tenderness [14] and the other on swelling, as previously described [12], a visual analogue scale (VAS) for pain, the disability index of the modified Stanford Health Assessment Questionnaire (HAQ) [15], haemoglobin (Hb), ESR and rheumatoid factor (RF). A disease activity score (DAS) was based on three variables (both articular indices and ESR) as originally described [16]. Standard radiographs of the hands and feet at presentation and yearly were digitized, stored on CD-ROM and scored by one observer, as reported previously [17], using Larsen's scoring system [18]. HLA-DRB1 type was assigned using a commercial reverse hybridization method on DNA extracted from stored blood samples (Dynal Biotech, Oslo, Norway), and the number of copies of the RA-related SE was determined [19]. In 40 HLA-typed patients, SE status was not ascertained. HLA typing was not possible when it proved difficult to obtain second samples from patients whose stored blood was either lost or damaged following storage problems at two centres (n = 179). Analysis of genetic data did not include the 23 non-Caucasoid patients (2%; Asian 14, Negroid 9).

Treatment profiles
All centres followed the framework of the published UK guidelines for the management of RA [20], which include the provision of therapy services, appropriate orthopaedic interventions, and early and sequential use of disease-modifying anti-rheumatic drugs (DMARDs), together with symptom-relieving measures and judicious use of steroids. Combination therapy was used in severe, non-responsive RA. DMARDs were chosen according to the physician's preference, although dosage schedules employing graduated regimens to maximum doses were agreed previously according to standard practice for each drug.

Outcome measures
All in-patient episodes were documented and details of all soft tissue, tendon or joint surgery as a result of RA were recorded prospectively according to the Office of Population Census and Surveys [21]. For purposes of analysis, these were grouped into major (hip, knee, shoulder, elbow joint replacements, or cervical spine fusion), intermediate (excision arthroplasties, synovectomies, arthrodeses, replacement of small joints of hands or feet, or a combination of these) or minor (e.g. carpal tunnel decompression, nodule removal, knee arthroscopy) categories. Medical records were checked to confirm details of dates when patients were first referred to, and seen by orthopaedic surgeons, dates of surgery, length of stay in hospital, and all postoperative complications. All extra-articular, coexistent musculoskeletal and comorbid conditions were recorded prospectively according to ICD10 [21].

Statistical analysis
Summary statistics have been used to demonstrate the differences in clinical features between types of orthopaedic interventions. Continuous variables were expressed as the median and interquartile range, or as the mean and 95% confidence interval (CI), and the Mann–Whitney U test was used to show differences between surgical groups. Odds ratios (OR) with 95% CI were used to demonstrate the association between surgical outcomes at 5 yr and clinical features at baseline and at 1 yr, for which the worst quartile was used as the cut-off for continuous variables.

Patient sample
Of 1236 patients recruited by the year 1997, 1064 (86%) were followed for at least 5 yr. Median duration of symptoms of RA prior to presentation to rheumatology clinics (study entry) was 6 (4–11) months, thus indicating early RA. There were 354 men (33%) and 710 women (67%) and median age of onset was 55 yr (range 17–84 yr, men 57 yr, women 54 yr). At baseline, 662 (62%) were positive for RF and 269 (25%) erosive on X-ray, and 741 (70%) fulfilled the minimum of four ACR criteria. By 5 yr of follow-up, 888 (83%) patients had received at least one DMARD, started at a median of 2 months (68% within 3 months and 87% by 12 months), consistent with early treatment policies. The remaining patients (17%) were managed with non-steroidal anti-inflammatory drugs (NSAIDs) and/or low-dose steroids. Overall use of these drugs over 5 yr was as follows: sulphasalazine, 54%; methotrexate, 18%; intramuscular gold, 13%; d-penicillamine, 9%; antimalarials, 4%; others (2%). Forty-nine per cent of DMARD-treated patients required more than one drug. Steroids in doses of >=7.5 mg daily for >=12 months were used in 166 (16%) patients. A five-year follow-up was not achieved in 172 (14%) patients: deceased (n = 60), 35%; moved (n = 16), 9%; declined follow-up, mainly for social and work related reasons (n = 19), 11%; remission (n = 6), 4%; lost to follow-up (n = 71), 41%. Disease characteristics of these patients were similar to those in a more detailed previous report [12].


    Results
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
Type of surgery (Table 1)
One hundred and eighty-one (17%) patients underwent orthopaedic surgery for a total of 264 procedures. One hundred and twenty-three had one operation, 38 had two operations, 15 had three and five had four. Major joint replacement surgery was performed in 75 patients (7%, between-centre variation 3–10%), of whom 15 had two or more large joints replaced. Fifty-one (5%, 3–11%) underwent 71 intermediate-type operations of wrist, hands or feet, mainly excision arthroplasties, synovectomies, arthrodeses, or combinations of these; 17 of these patients had two or more such procedures. Details of all procedures are shown in Table 1. Five patients underwent bilateral joint surgery at one operating session (two each for bilateral knee and hip replacements, one bilateral metatarsal excision arthroplasty).


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TABLE 1. Number and percentage of all orthopaedic interventions grouped by type

 
Time from baseline visit to surgery (Fig. 1)
The median time from baseline to first orthopaedic intervention was 36.5 months [interquartile range (IQR) 24–48] and only minor variations were seen according to type of surgery. This was 37 months for first large joint replacements (IQR 28–52), 41 months (27–52) for intermediate-type surgery (mainly hand or foot excision arthroplasties), and 36.5 months (20–49) for minor procedures. Variation of median times between Early Rheumatoid Arthritis Study Group (ERAS) centres was 33–48 months for major, 30–44 months for intermediate and 13–48 months for minor surgery. The possibility that these different surgical rates were due to differences in waiting times for surgery between ERAS centres was explored by comparing the time from the decision to refer for an orthopaedic opinion to the time of the surgical procedure. The overall median waiting time was 6 months, with between-centre variation of 2–12 months, and for major, intermediate and minor surgery the times were 7 (5–12), 6.5 (5–12) and 2 (1–5) months respectively. The main delay for major surgery was the wait from orthopaedic assessment to surgery (median 4 months, IQR 2–10), not the delay in seeing a surgeon (median 1 month, IQR 1–3). One centre was mainly responsible for this wide variation in waiting times for large joint replacements, and when this outlier was excluded (median 12 months) the between-centre median range was 5–6.5 months. Fifteen procedures were performed in the private sector (six major joint replacements, six excision arthroplasties, three minor). Median waiting times for surgery in these patients was 3 months, but the effect on overall waiting times was minor. The possibility that waiting times underestimated the actual need for surgery was checked by establishing numbers of patients on waiting lists, in whom surgery was performed after 5 yr. Nine patients were waiting for surgery: four for hip replacements and one each for knee and elbow replacements, one for metatarsal excision arthroplasties, and the remaining two for minor surgery. When these were included, the need for major surgery by 5 yr showed less variation between centres (5–8% for major surgery).



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FIG. 1. Time to surgery. Time in months from baseline (study entry) to surgery, grouped by type of orthopaedic intervention. At the top of the graph, these are major, intermediate and minor procedures. The more frequent specific interventions include hip and knee replacements and hand and foot joint surgery. Vertical bars represent the median, horizontal bars the quartile ranges, and whiskers the outliers.

 
Hip fractures and coexistent osteoarthritis
Orthopaedic surgery was performed on 21 occasions where pathologies other than RA were also present. Osteoarthritis (OA) of the hip was ascertained clinically and radiologically in seven of 48 (15%) who underwent total hip replacement (THR), five of whom had OA hip diagnosed at first presentation. Ten patients required surgery for osteoporotic hip fractures, five needing THRs. OA knee was present in 7/26 (27%) who had total knee replacements (TKR), and mechanical or degenerative changes were present in 5/17 minor orthopaedic procedures or arthroscopies. One patient had surgery for predominantly OA hands and another for OA feet. The significant differences in clinical features between the THR/TKR patients with OA or fracture and those without were age at onset (mean age 65 and 58 yr respectively, P<0.05) and ESR (mean baseline ESR was 41 and 61 mm/h respectively, P<0.03), which suggested less active disease in the former. The relative importances of degenerative and inflammatory factors and the primary and secondary pathologies for joint replacements were not always clear-cut in these patients. Combined or accelerated pathologies were considered the most likely, except in nine patients (five THR, two TKR, one OA hands and one OA feet) in whom OA was diagnosed before the onset of RA. This possible confounding factor was accounted for in the analysis of clinical and laboratory factors.

Comparison with national figures
Figures for surgical rates for THR and TKR were analysed from national 1996/7 UK Department of Health Hospital Episodes Statistics data, which include primary and secondary diagnoses, and from which it is possible to obtain figures for individual NHS Trust hospitals. Unfortunately, due to huge variations in the frequency of coding for secondary diagnoses for THR and TKR, it was not possible to obtain the background surgical rates for OA in the presence of RA.

Clinical and laboratory risk factors for surgery
Table 2 summarizes the clinical characteristics of all patients at baseline. These are similar to those of other early RA cohorts. They are also shown according to the type of interventions performed by 5 yr of follow-up.


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TABLE 2. Baseline features in whole cohort and by type of surgery by 5 yr

 
Univariate analysis
Table 3 Shows the odds ratios and 95% CI for clinical and laboratory factors (worst quartiles as cut-off for continuous variables) for all types of joint and tendon surgery, and separately for major joint replacement and intermediate-type surgery. Variables at baseline and at 1 yr of follow-up are shown if OR > 1 (and lower 95% CI >=1). Risk factors for joint replacement were low Hb and high scores for ESR, Larsen erosion score for hands and feet, HAQ and DAS, and older age. Predictive values were stronger at 1 yr than at baseline. The values shown refer to surgery for RA, excluding patients in whom surgery was not primarily for RA. However, the same risk factors were seen when all replacement surgery was analysed, although this showed slightly lower ORs for all variables except age (OR 2.4, CI 1.5–3.8) and HLA-DR SE (OR 2.4, CI 1.0–5.4). Hand and foot joint surgery (excision arthroplasties, synovectomies and fusion) was associated with female gender and high values for joint score, DAS, erosions and HAQ at baseline. No significant associations were seen for minor surgery. However, one and two copies of the SE were both related to orthopaedic surgery. Separate analysis of multiple major and/or intermediate type surgery (n = 36) did not reveal any significant predictive features, although numbers were small.


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TABLE 3. Risk factors for surgery

 
Multivariate analysis
All baseline and 1-yr clinical and laboratory variables were investigated as possible predictors for any orthopaedic surgery, and separately for major or intermediate-type operations. Stepwise logistic regression selected a combination of the following first-year variables as the most powerful predictors for any type of surgery by 5 yr: ESR, DAS, function, and HLA SE. The two upper quartiles for ESR and function and the upper quartile for DAS carried significant additional risk for surgery (see Appendix). This model resulted in correct prediction overall of 69% (specificity 87.3%, sensitivity 36.2%, positive predictive value 61.6%, negative predictive value 70.9%). To test the validity of this model, data were split randomly (60%/40%) and, using the same variables, logistic regression predicted correctly 68.9% in the training sample and 67.7% in the testing sample. We were unable to develop a successful model for major or intermediate-type surgery, possibly because of small numbers.

Progress of RA and orthopaedic outcome
There were no immediate postoperative deaths and all patients recovered from any postoperative complications. However, three patients died within 12 months after hip fractures, two with heart failure and one with bronchopneumonia. The median duration of hospital in-patient stay was 14 days (10–17) for major joint surgery, 5 days (3–7 days) for intermediate-type surgery and 2 days n = (1–3) for minor surgery, with little variation between centres. Long stays were due to major postoperative complications, which included septic arthritis (n = 1), wound infection (n = 5), prosthetic loosening (n = 1), transfusion reaction (n = 1), jaundice (n = 1), or general medical and rehabilitation problems (n = 8).

How much difference surgery made to functional ability is difficult to evaluate because of the observational nature of the study and because interventions were not randomized. The major and intermediate surgery groups did have worse 5-yr functional grades (FG) (FG III/IV 40 and 20% respectively) compared with the rest of the cohort (12%, P<0.00001). However, the surgical group already had worse function at presentation, and function deteriorated over 5 yr in the major joint replacement group. Figure 2 displays graphically measures of function (HAQ) and disease activity in all patients at baseline and for 5 yr of follow-up for each type of broad surgical group compared with those who did not undergo orthopaedic surgery. Laboratory measures improved overall from baseline over the first year, and stabilized over the next few years, as we have reported previously [11, 12]. Major and intermediate-type interventions were performed mainly between 27 and 52 months. Mean baseline Hb, ESR, Larsen erosion score, DAS and HAQ were worse in the joint surgery groups and deteriorated despite surgery. Deterioration in functional grade (FG at presentation minus FG at 5 yr) seen in the major and intermediate surgical groups (31%) was only slightly more frequent compared with the non-surgical group (22%, P<0.05). Joint surgery affected paid employment in patients who were working at presentation. Of all patients who required surgery, 73 patients were in paid work (40%; manual work, 29 patients). Twenty-one underwent intermediate and 20 major surgery, and 11 and 13 respectively stopped work permanently while waiting for or following surgery. In all but one, this was due to the effects of RA, including the need for surgery and not other factors (e.g. redundancy, age-related retirement). A further four patients changed to either lighter or part-time work. Of the remaining patients who continued in employment, six needed more than 6 months off work because of surgery. This study was not designed to assess the beneficial effects of surgery, and it has not been possible to test the assumption that patients are likely to improve following surgery or suffer worse symptoms and functional ability without it. However, given that the surgical group had worse RA at presentation, it is possible that the disease measures shown above in these patients would have been worse without surgery.



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FIG. 2. Clinical and laboratory variables by types of orthopaedic interventions. The mean and 95% CI for HAQ, DAS, Hb and ESR are shown at baseline and yearly intervals for three categories of orthopaedic interventions, and compared with the remainder of the cohort.

 
Missing data
One of the standard clinical or laboratory baseline variables was missing in 49 (5%) patients, and six had more than one missing item. HLA genetic typing data were missing in 179 (17%) for the technical reasons described above. There were no significant differences in demographic or clinical features between these patients and those with a complete data set (data not shown). In view of this, we conclude that the problem of missing data is unlikely to alter our findings, although we cannot rule out this possible source of bias, as described previously [12].


    Discussion
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 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
This study highlights the occurrence of severe joint failure that may occur within a few years from the onset of RA, despite early use of conventional medical therapy. Total hip or knee replacements for RA were required in 7% of our patients, at a median of 37 months from presentation. Shoulder and elbow replacements (n = 3 each) and one cervical spine fusion occurred later, at a median of 53 months, in line with clinical experience.

Correction for between-centre waiting times showed minor differences only for rates of joint replacements in ERAS centres. Fifteen patients needed more than one joint replacement by 5 yr of follow-up. Hand and foot joint surgery, mainly excision arthroplasty, synovectomy and/or arthrodesis, was performed in a further 5%. As far as we are aware, this is the first report of a regional comparison of the occurrence and type of orthopaedic interventions and waiting times for surgery in early RA in England. Waiting times for surgery were shorter than expected for the UK and this may reflect the special interest in early RA of the rheumatologists involved in this study and the use of combined clinics with orthopaedic surgeons.

Comparison with other longitudinal studies is limited because few are genuine inception cohorts, and the type of and threshold for orthopaedic interventions have changed considerably in recent years. A Swedish prospective study in 1994 [5] reported a subgroup of 14% (nine patients) who required joint replacement within 5 yr. A Finnish report [1], based on a cross-sectional community study of 103 patients, reported that 20% of patients required surgery by 10 yr of disease duration. The US study [3], which reported on patients with very variable disease duration at entry, indicated that 25% of patients undergo total joint arthroplasty within 22 yr. Extrapolating the rates of major joint surgery by 5 yr of RA from these studies revealed rates similar to our findings: about 7–10%.

Comparisons with national figures are difficult because these reflect surgical rates and waiting times mainly for OA rather than RA. Analyses of national databases have been limited by incomplete and inaccurate data coding for underlying primary and secondary diagnoses [6, 7]. Similar reports to ours have not examined the prevalence of OA or fracture as a sole or additional factor for hip or knee replacement surgery in RA. This is important, not only to establish the real frequency of joint surgery for RA, but also to show that, by correcting for this in risk analysis, age of onset of RA was lessened as a prognostic factor, and markers of disease activity and severity (HAQ, DAS, ESR, Hb) were in fact strengthened.

Orthopaedic interventions were more likely in our patients with one or two copies of the SE. Factors at presentation associated with major joint replacement surgery for RA were low Hb and high ESR, HAQ, DAS and radiological erosion scores. In contrast to this, risk factors at baseline for excision arthroplasties and synovectomies of hands, wrists, elbows and feet were female gender, joint score, DAS and erosions. These variables at 1 yr of follow up had stronger predictive capabilities. These clinical and laboratory factors are all recognized markers of disease activity and severity but their predictive abilities varied according to type of surgery. These are significant findings, which may have clinical utility. We have previously reported the value of baseline HAQ in predicting 5-yr functional outcome [11], work disability [22] and mortality in these patients [23]. Patients in the worst quartile for HAQ at 1 yr were more than three times as likely to need joint replacement within 5 yr, and twice as likely to need hand or foot surgery. Standard laboratory measures (Hb and ESR) were, however, stronger predictors of replacement joint surgery. At 1 yr, patients in the worst quartiles for Hb (< 11.5 g/l) and ESR (> 45 mm/h) were respectively more than four and five times likely to require major joint surgery. In the first year of RA, an important therapeutic target includes suppression of these measures of disease activity in order to reduce the eventual need for surgery.

Several clinical and laboratory variables, which primarily reflect disease activity, have been reported to predict joint replacement, in univariate and multivariate analysis [35]. Similar to our findings, Wolfe et al. [3] reported low Hb as a risk factor for joint replacements, an unexpected finding as normally this does not perform well as a predictor of outcome. Our study also identified high ESR as a powerful predictor for major surgery, especially at 1 yr, an association also reported in a 20-yr outcome study [24]. Kuper et al. [25] reported that radiological damage of the large joints, especially the hips and knees, occurred in 50% of cases of early RA followed for 6 yr and that this correlated with acute-phase measures (area under the curve for ESR and C-reactive protein) and with radiographic changes in hands and feet. In the west of Scotland, patients homozygous for SE were five times more likely to require major surgery within 15 yr [4], in the other patients with one SE or no SE, a high ESR was an important risk factor, and prediction was correct in 73%. Sixty per cent of RA patients homozygous for the disease epitope eventually needed a joint replacement in a tertiary referral centre in the USA, compared with 25% of heterozygotes [2]. Eberhardt et al. [5] reported from the only other inception cohort that patients homozygous for SE were three times more likely to require surgery. Although the criteria recommended for developing prognostic factors for RA have largely been met in our study [26], the associations we report are similar but were generally weaker compared with the above studies. Possible reasons for these differences include variations in study design and the fact that most other studies have been either cross-sectional or, if prospective, not inception cohorts, so that few have analysed predictive features at first presentation of RA. Duration of RA has been variable in other reports, and as joint failure requiring surgery is an uncommon event within 5 yr, this may explain the weaker association we found with SE. Few studies have addressed confounding factors such as OA and fracture, and few have reported on orthopaedic interventions other than large joint replacements.

Selection bias is unlikely, and this is the main strength of this study because recruitment was direct from primary care physicians in nine different regions, at the earliest stages of RA and prior to use of second-line drugs. Because of this and the minimal exclusion criteria, which are so restrictive in clinical trials, the study reflects actual clinical practice. Yearly standardized assessments were made over the same time frame, and good follow-up was achieved. Possible sources of bias in this study arise as a result of left-censoring (milder RA not being referred to hospital out-patients), right-censoring (more severe RA not surviving 5 yr), and treatment effects. Although the subtle effects of the different DMARDs that were tried first and subsequent changes cannot be accounted for, our patients were being treated early in a conventional manner [12]. Only seven patients who had surgery were not included in this analysis, because they were followed for less than 5 yr (six deceased, one moved), one with hip and knee joint replacements, one with forefoot arthroplasty, one with wrist synovectomy, one with hip fracture, two with knee arthroscopy and one with carpal tunnel decompression.

This study provides a view of the progress of early RA treated with conventional drugs in a closely monitored group of patients in different regions of England and illustrates the magnitude of RA-attributed joint damage severe enough to require surgical intervention. Patients with RA and those involved in their care and treatment need information on how the disease may affect major aspects of their lives. We have reported previously on the importance of both cumulative disability [12] and work disability in these patients [22]. The greater details of orthopaedic interventions described here provide a basis for discussion with patients concerning practical issues and prognosis. These exact figures are also important in planning for the kind and extent of services required for managing RA even in early stages. Treating RA was reported to have cost £1.256 billion in 1992, or approximately £2600 per patient [27]. Direct resource consumption represented around 20%, of which in-patient care represented 28%. Orthopaedic costs have not been covered in studies on the cost of RA in the UK, although identifying the different components of direct costs is one recommendation in a review of this subject [28]. The annual direct costs per patient from in-patient/out-patient care varied from £466 to £1721 depending on HAQ in a recent estimate of the costs of RA using the ERAS data set [29]. The costs of DMARDs and drug monitoring were less (£357–558), but this ratio could change with the use of new biological agents, the cost of 1 yr of treatment being similar to that for hip or knee replacements (£8–10 000).

An intriguing question is whether the need for major joint replacement or hand/foot arthroplasties will lessen with improved medical therapy. The assessment of drug treatment effects is limited in observational studies because of non-random assignment of therapy. Nonetheless, the newer agents can only be described as ‘disease-modifying’ if they can be shown to alter cumulative disability in the long term, and joint surgery is a well-defined and easily quantifiable outcome. The ERAS database will permit a comparison of this outcome following the use of the new and expensive biological agents with a well-described historical standard, reflecting the management and costs of RA over years during the 1990s.

In summary, we found that 11% of patients underwent large- or small-joint surgery within 5 yr of presentation of RA. The worst quartiles of Hb, ESR, DAS, erosion score and HAQ at presentation have predictive value for this outcome, with greater clinical utility at 1 yr. Low Hb was an unexpected and powerful predictor (OR 4.4), second only to ESR (OR 5.9). Further work is required to determine the clinical utility of these prognostic markers.

The authors have declared no conflicts of interest.


    Appendix
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 
Prognostic index for orthopaedic intervention
Dependent (outcome) variable = any orthopaedic procedure by 5 yr.

Independent variables = all baseline and first-year clinical and laboratory variables.

Categorical variables and continuous variables (as quartiles, 1–4) were entered into a logistic regression model. Adjusted odds ratios are shown, with 95% CI. ORs for each category are compared with the first.


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Variables in equation

 

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Details of authors

 

    Notes
 
A full list of authors from the Early Rheumatoid Arthritis Study Group (ERAS) is given in the Appendix.


    References
 Top
 Abstract
 Introduction
 Patients, materials and methods
 Results
 Discussion
 Appendix
 References
 

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  8. Moreland LW, Schiff MH, Baumgartner SW et al. Etanercept therapy in rheumatoid arthritis. Ann Intern Med 1999;130:478–86.[Abstract/Free Full Text]
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Submitted 6 June 2003; Accepted 24 September 2003