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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Objective

To evaluate the contribution of assessing forefoot joints to the measurement range and measurement precision of joint counts in early rheumatoid arthritis (RA) using item response theory.

Methods

Baseline measures of tender and swollen joint counts were analyzed in 459 early RA patients from the Dutch Rheumatoid Arthritis Monitoring remission induction cohort. The contribution of forefoot joints was studied by evaluating their effect on the measurement range and measurement precision of measures based on 28-joint counts. In addition, the alignment between the patient and joint distributions was investigated to determine whether the forefoot joints were informative for measuring joint tenderness or swelling of an early RA patient.

Results

In total, 233 patients (50.76%) experienced tenderness and 200 patients (43.57%) experienced swelling in ≥1 forefoot joint. Forefoot joints were more informative for measuring joint tenderness than joint swelling, but did not significantly improve the measurement range and measurement precision of the 28-joint counts. Furthermore, including forefoot joints did not remove the existing discrepancy between the joint and patient distributions in both joint counts.

Conclusion

Forefoot joints were frequently affected on an individual level, but did not significantly improve the measurement range or precision of 28-joint counts in patients with early RA. From a measurement perspective, reduced joint counts are appropriate for use on a population level. The contribution of assessing forefoot joints on an individual level requires further investigation. Additionally, the results should be cross-validated in patients with longer disease durations to determine whether the pattern of joint involvement is similar in later stages of RA.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The Disease Activity Score for 28 joints (DAS28) (1) is a widely used index measure for assessing the disease activity of individual rheumatoid arthritis (RA) patients and for evaluating treatment effectiveness aimed at reaching or sustaining a state of remission. However, despite the frequent involvement of the 28 joints included in the DAS28, there are data to support that the omission of the forefoot joints causes the DAS28 to underestimate actual disease activity in early RA patients predominantly with disease activity in the feet (2). Additionally, the DAS28 remission criteria might not reflect a true state of remission, due to the presence of residual tenderness or swelling in omitted joints (3). Consequently, the cutoff point for DAS28 remission often has been criticized (3, 4).

From a measurement perspective, the high prevalence rates of painful and swollen forefoot joints (5, 6) might provide relevant additional quantitative clinical information for assessing and monitoring the status of patients with RA. However, practical constraints, extra administration time, assessment difficulty, and the recognition that abnormalities in the feet may often result from processes other than RA are all reasons for their frequent exclusion from the joint counts (7–10). Furthermore, various studies have shown that reduced joint counts that exclude the forefoot joints appear to be as reliable and valid as more comprehensive joint counts (1, 5, 7, 11). Nevertheless, the exclusion of the forefoot joints remains a topic of debate and research.

When approaching this debate from a measurement perspective, most studies used methods from the classical test theory to examine the contribution of forefoot joints, for instance, by examining the correlation between reduced and extended joints counts (5). However, classical test theory does not provide insight into the effect the inclusion of forefoot joints has on the measurement range and measurement precision of the total joint count, an insight that can be obtained by applying a different measurement perspective, called item response theory (IRT). Therefore, the aim of this study was to evaluate the contribution of assessing forefoot joints in patients with early RA using IRT.

Significance & Innovations

  • Including forefoot joints does not significantly improve the measurement range or measurement precision of the 28 tender and swollen joint counts in patients with early rheumatoid arthritis.

  • Including forefoot joints does not remove the existing discrepancy between the joint and patient distributions of the 28 tender and swollen joint counts.

  • From a measurement perspective, reduced joint counts are appropriate to use on a population level.

  • The contribution of assessing forefoot joints on an individual level could be important clinically and requires further investigation.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Patients.

Patients participated in the Dutch Rheumatoid Arthritis Monitoring (DREAM) remission induction cohort (12), a multicenter cohort that was started in 2006 to evaluate the effect of a protocolized treatment strategy aiming at a state of remission in early RA patients in daily clinical practice. Patients were eligible for inclusion at the moment they were clinically diagnosed with RA, if they were ages ≥18 years, and if they had never received disease-modifying antirheumatic drugs or prednisolone before. The ethics committee of each participating hospital evaluated the study protocol. Since the study data were gathered during daily clinical practice, the ethics committees determined no approval was required, which is in accordance with the Dutch Law. Nevertheless, informed consent was obtained from each patient.

Measures.

Disease activity was assessed by a trained rheumatologist or nurse practitioner at each visit using extensive joint counts, including 44 joints for the measurement of joint tenderness and joint swelling, the erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP) level, and a 100-mm visual analog scale (VAS) for general health. The 28- and 38-joint counts for tenderness and swelling, used for analyzing the contribution of the forefoot joints, were derived from these 44-joint counts. The DAS28 score was computed with the 28 tender joint count (TJC28), 28 swollen joint count (SJC28), ESR, and VAS for general health scores. Only baseline measures were used for analyses.

The 28-joint counts on tenderness and swelling include the shoulder (n = 2), elbow (n = 2), wrist (n = 2), metacarpophalangeal (MCP; n = 10), proximal interphalangeal (PIP; n = 10), and knee (n = 2) joints. The 38-joint counts also include the 10 metatarsophalangeal (MTP) joints of the feet. All of the joints were scored dichotomously.

The Boolean-based American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition of RA remission was used to determine remission, since this criterion can be used with both the 28- as well as the 38-joint counts (13).

Statistical methods.

To analyze the contribution of the forefoot joints, an IRT model (the generalized partial credit model [GPCM]) (14) was applied. Both the 28- and 38-joint counts of tenderness and swelling had to fit the GPCM before the contribution of the forefoot joints could be analyzed. This fit was analyzed with Lagrange Multiplier Q1 tests (15), where absolute effect sizes of <0.10 were seen as an indication of good item-model fit (16, 17).

Next, the reliability and corresponding measurement precision of the joint counts with and without forefoot joints were evaluated and compared. IRT global reliability is equivalent to Cronbach's alpha, but based on IRT scores (theta) instead of raw scores (18). The theta scores are scaled at approximately 0 and correspond to the degree of joint tenderness or swelling a patient experiences. Reliabilities of >0.7 were considered sufficient for group use, whereas values of >0.85 were deemed necessary for individual use (19).

Local reliability and measurement precision of both the total joint counts as well as their individual joints were derived from 2 types of information curves (18, 20). First, the test information curves (TICs) were investigated to determine the range on the underlying scale where the total joint counts can reliably (precisely) measure a patient's degree of joint tenderness or swelling, where reliability = 1 − (1/test information at θ) and the precision of the estimated theta is the reciprocal of the test information (Var(θ) = 1/test information at θ) (18). TICs of joint counts with and without forefoot joints were compared to determine the effect of including forefoot joints on the measurement precision and measurement range of the total instrument. A TIC is a sum of the individual item information curves (IICs). These show the contribution of the individual joints to the estimation of joint tenderness or swelling. IICs of the forefoot joints were compared to the IICs of the other joints to determine their individual contribution to the total instrument and to evaluate for which patients they provide the most information.

Finally, the alignment between the patient and the joint distributions was evaluated. Ideally, the mean scores of these distributions should be relatively close to each other and the distributions should approximately cover the same range of the scale. Joints measuring outside the range of the patient distribution are less informative about the patients' joint tenderness or swelling than joints measuring inside this range.

IRT analyses were performed with the statistical program MIRT (21). Full item parameter calibrations are available from the corresponding author upon request. Patient and joint distributions were plotted with SPSS, version 18.0.

RESULTS.

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Patient characteristics.

The cohort included a total of 459 patients for analysis, predominantly consisting of women (62.31%). Most had active disease at inclusion, with a mean ± SD DAS28 score of 4.69 ± 1.31, and they experienced their general health as rather low, with a mean ± SD score of 49.83 ± 25.03 (Table 1). On average, patients had 6 tender and 7 swollen joints on the 28-joint counts, which increased to 8 tender and 9 swollen joints on the 38-joint counts. Forefoot joints were commonly affected, with 233 patients (50.76%) experiencing tenderness and 200 patients (43.57%) experiencing swelling in ≥1 of the forefoot joints. Based on both the 28- and the 38-joint counts, 7 patients were in remission according to the new Boolean-based ACR/EULAR definition of remission. None of the patients in remission experienced tenderness or swelling in their forefoot joints.

Table 1. Baseline characteristics of the 459 rheumatoid arthritis patients included in the cohort*
 Value
  • *

    Values are the mean ± SD unless otherwise indicated. DAS28 = Disease Activity Score in 28 joints; TJC = tender joint count; SJC = swollen joint count; VAS = visual analog scale; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; MTP = metatarsophalangeal.

Age, years57.76 ± 14.70
Women, no. (%)286 (62.31)
DAS28 score4.69 ± 1.31
TJC285.60 ± 5.55
TJC387.90 ± 7.26
SJC287.39 ± 5.60
SJC389.15 ± 6.73
VAS for general health, mm49.83 ± 25.03
ESR, mm/hour29.16 ± 20.89
CRP level, mg/dl21.11 ± 35.80
≥1 tender MTP joint, no. (%)233 (50.76)
≥1 swollen MTP joint, no. (%)200 (43.57)
>1 tender MTP joint, no. (%)196 (42.70)
>1 swollen MTP joint, no. (%)170 (37.04)

Fit and global reliability.

The results showed a good fit to the GPCM for both the 28- and 38-joint counts, since all of the effect sizes were well below 0.10 (Table 2).

Table 2. Fit of the joint counts to the generalized partial credit model and associated global reliability levels*
InstrumentReliabilityMaximum effect size of Lagrange Multiplier Q1 tests over items
  • *

    TJC = tender joint count; SJC = swollen joint count.

TJC280.8270.03
SJC280.8600.04
TJC380.8610.06
SJC380.8690.04

All of the joint counts showed reliabilities acceptable for individual use (r = >0.85) except for the TJC28, which was sufficiently reliable for group use, but slightly below the level for individual use. Reliability of the 28-joint counts only marginally increased when the forefoot joints were added to the instrument.

Local reliability and measurement range.

Both the TJC28 and the SJC28 only measured reliably for patients with a moderate to high degree of joint pain (r = >0.80 for −0.3 < θ < 2.8 and −0.7 < θ < 2.2, respectively). Most information was provided by the small MCP and PIP joints, whereas larger joints contained only a limited amount of information. Although Figures 1 and 2 demonstrate that these measurement ranges became slightly broader after inclusion of the forefoot joints (TJC38: r = >0.80 for −0.5 < θ < 3.1; SJC38: r = >0.80 for −0.8 < θ < 2.7), the forefoot joints did not provide a high amount of information to the SJC, indicating that they do not contribute much to the estimation of joint swelling. Furthermore, in both joint counts, the forefoot joints mainly contained information along a range of the underlying scale already covered by the joints of the TJC28 and SJC28. (Graphical representations of the separate calibrations of the 28- and 38-joint counts are available from the corresponding author upon request.)

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Figure 1. Test and item information curves of the tender joint counts (TJCs). The top graph shows the test information curves of the TJC28 and TJC38 with associated local reliability levels (r). The bottom graphs show the item information curves of the TJC38 for the joints on the left side (left column) and right side (right column) of the body. Sho = shoulder; Elb = elbow; Wri = wrist; MCP = metacarpophalangeal; PIP = proximal interphalangeal; MTP = metatarsophalangeal.

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Figure 2. Test and item information curves of the swollen joint counts (SJCs). The top graph shows the test information curves of the SJC28 and SJC38 with associated local reliability levels (r). The bottom graphs show the item information curves of the SJC38 for the joints on the left side (left column) and right side (right column) of the body. Sho = shoulder; Elb = elbow; Wri = wrist; MCP = metacarpophalangeal; PIP = proximal interphalangeal; MTP = metatarsophalangeal.

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Patient–joint distributions.

TJC38.

Figure 3 shows a discrepancy between the patient and the joint distribution of the TJC38. Where the joint distribution spreads from 0.65 to 3.07, the patient distribution is much broader (spreading from −1.48 to 3.51). The items cluster together in a small range at the right half of the person distribution. Consequently, patients with only a minor degree of joint tenderness are not adequately measured by the included joints. The lower measurement precision for these patients also diminishes the instrument's ability to discriminate between patients with varying degrees of joint tenderness.

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Figure 3. Graphical representation of the patient distribution (top graph) and the joint distribution (bottom graph) of the 38 tender joint count. Shaded dots in the joint distribution show the forefoot joints. Measurement precision is optimal at the scale location of each joint.

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The 2 joints located most to the right are the elbow joints, restricting their relevance to the small proportion of patients located in the right tail of the person distribution in particular. The forefoot joints, on the other hand, appear to be relevant for a larger proportion of the early RA sample, since they are located more in the middle of the patient distribution. However, their contribution to the measurement of disease activity is limited because they function along a range already covered by other joints of the instrument.

SJC38.

The SJC38 also shows a large discrepancy between the patient and joint distributions (Figure 4). The patient distribution ranges from −1.78 to 4.03, whereas the joint distribution spreads from −0.20 to 8.95. Five joints fall outside the range covered by the person distribution (elbows, shoulders, and right knee), diminishing their relevance to the early RA sample. Of the 10 forefoot joints, 4 joints function along a range of the scale not yet covered by other joints. Nevertheless, inclusion of these forefoot joints is only relevant for a small proportion of the patients, since they measure most precisely for the patients located in the right tail of the person distribution.

thumbnail image

Figure 4. Graphical representation of the patient distribution (top graph) and the joint distribution (bottom graph) of the 38 swollen joint count. Shaded dots in the joint distribution show the forefoot joints. Measurement precision is optimal at the scale location of each joint.

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The results showed no relevant effect of the inclusion of forefoot joints on a population level of patients with early RA, confirming conclusions from previous studies (8, 22). The global reliability was already acceptable for group use when the forefoot joints were excluded, the measurement range did not become significantly broader after the inclusion of forefoot joints, and the discrepancy between the joint and the patient distribution for both the TJC and the SJC remained large.

On an individual level, however, the assessment of forefoot joints might be relevant for a large proportion of the individual patients, given the high prevalence rates of affected forefoot joints in the early RA sample, which was also found by van der Leeden et al (6). Since the anchor of remission is rapidly becoming more important within rheumatology, these results show the importance of including forefoot joints. Moreover, researchers or clinicians interested in tracking the disease course of an individual patient might want to include the forefoot joints in both the TJC as well as the SJC, since these joints can contain important information about and might give a more complete image of the development of the patient's disease (23). These results are consistent with earlier findings emphasizing the importance of forefoot joints on an individual level (2, 22). Nevertheless, the information curves did show a large discrepancy between the forefoot joints' information value in the TJC and SJC. Where the forefoot joints appeared to be informative for the TJC, their information value for the SJC was almost negligible. These results suggest that inclusion of the forefoot joints might be more useful for measuring an individual patient's degree of joint tenderness than for measuring his or her degree of joint swelling. The limited information value of forefoot joints in the SJC might be explained by the clinical experience that the assessment of swelling in the forefoot joints is more difficult than in other joints (8). Nevertheless, the results did show that 4 forefoot joints of the SJC functioned along a range of the scale not yet covered by other joints. Although inclusion of these forefoot joints was only relevant for a small proportion of the patients, diminishing its relevance on a population level, it might have significant implications on response criteria and early classification of individual patients. On the other hand, the joints of the elbows, shoulders, and right knee fall outside the range covered by the person distribution, casting doubt on their relevance for the early RA sample. Future work could focus more on the relevance of these large joints that are included in the reduced joint counts and on the relevance of the forefoot joints on an individual level.

This study gives new methodologic support to earlier research showing that the reduced 28-joint counts can be useful for assessing baseline disease activity at a population level (e.g., as indicators of hospital performance or in clinical trials), but that more extensive joint counts might be preferable for following the disease course of the patients in daily clinical practice (5, 23). Since foot joints, particularly the MTP joints, are commonly affected in RA (5), the main interest of this study was in the effect of the inclusion of forefoot joints on the measurement range and measurement precision of the joint count. Data were derived from 44-joint counts of tenderness and swelling, and consequently, other foot joints such as the tarsometatarsal joints and the tarsal joints within the midfoot were not included in this study. To make study results comparable to and consistent with the study by van Tuyl et al (8), the ankle joints were excluded as well and analyses were based on 38-joint counts. If the outcome of interest is the entire foot, however, future work should also focus on investigation of midfoot and hindfoot joint swelling and tenderness.

A limitation of this study is that, where previous studies evaluated misclassifications of RA disease activity due to the omission of forefoot joints (2, 8), this could not be evaluated in this study because only baseline measures were used with almost no patients in remission. Data from followup measurements must be analyzed in future research to determine the impact of the inclusion or exclusion of forefoot joints on RA disease activity classifications.

Another reason for analyzing followup measurements is to examine whether the results of this study are also applicable beyond patients with a recent diagnosis. The pattern of joint involvement at diagnosis might not necessarily resemble the pattern at later measurement points or posttreatment. Consequently, the results might not apply equally to patients in a later stage of RA treatment.

All of the participating patients were clinically diagnosed with RA. The finding that 7 of these patients were already in a state of remission according to the ACR/EULAR criteria despite having symptoms that led to a diagnosis of RA can be explained by the use of different classification instruments for the clinical diagnosis of RA and the determination of remission. To be classified as being in a state of remission, the Boolean-based ACR/EULAR criteria were used (13), which means that a patient had to have TJC, SJC, CRP level (in mg/dl), and patient global assessment (on a scale of 0–10) scores that were all ≤1. For a clinical diagnosis of RA, on the other hand, the 2010 ACR/EULAR classification criteria for RA were used (24). According to these criteria, RA is present when the patient experiences synovitis in at least 1 joint that cannot be explained any better by an alternative diagnosis. In addition, a total score of 6 or higher (with a maximum of 10) has to be obtained on the number and site of involved joints (score 0–5), the serologic abnormality (score 0–3), the symptom duration (score 0–1), and the elevated acute-phase response (score 0–1).

In conclusion, forefoot joints were frequently affected on an individual level, but the inclusion of forefoot joints did not significantly improve the measurement range or measurement precision of the TJC and SJC in patients with early RA. From a measurement perspective, reduced joint counts are appropriate to use on a population level. The contribution of assessing forefoot joints on an individual level could be important clinically, and requires further investigation. Additionally, the applicability of these study results should be examined beyond patients with a new diagnosis to determine whether the pattern of joint involvement at diagnosis resembles the pattern at later stages of RA.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Ms Siemons had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Siemons, ten Klooster, Taal, Glas, van de Laar.

Acquisition of data. Kuper.

Analysis and interpretation of data. Siemons, ten Klooster, Taal, Kuper, van Riel, Glas, van de Laar.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The authors would like to thank all of the patients for their participation in this study and the rheumatologists from the Medisch Spectrum Twente (Enschede), Ziekenhuisgroep Twente (Almelo, Hengelo), Universitair Medisch Centrum Groningen (Groningen), Isala Klinieken (Zwolle), TweeSteden Ziekenhuis (Tilburg), and UMC St. Radboud (Nijmegen) for patient recruitment and data collection.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS.
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES