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Rheumatology Advance Access originally published online on April 2, 2007
Rheumatology 2007 46(6):1020-1023; doi:10.1093/rheumatology/kem051
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Most people over age 50 in the general population do not meet ACR remission criteria or OMERACT minimal disease activity criteria for rheumatoid arthritis

T. Sokka, H. Mäkinen, P. Hannonen and T. Pincus1

Jyväskylä Central Hospital, Jyväskylä, Finland 1Vanderbilt University, Nashville, TN, USA

Correspondence to: T. Sokka, Arkisto/Tutkijat, Jyvaskyla Central Hospital, 40620 Jyvaskyla, Finland. E-mail: tuulikki.sokka{at}ksshp.fi


   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Objective. To analyse the proportion of individuals in the general population over age 50 who do not meet American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA) remission, and OMERACT criteria for minimal disease activity (MDA), and to compare results to RA patients.

Methods. A self-report questionnaire was completed by 1400 community control subjects and 1705 RA patients, including the Health Assessment Questionnaire (HAQ), gradual rating scales for pain, fatigue and global health, duration of morning stiffness and painful joints. The prevalence of 4/6 ACR remission criteria and 4/7 OMERACT criteria for MDA was analysed in community control subjects and patients with RA over age 50.

Results. For ACR criteria, 76% of control subjects reported painful joints, 37% morning stiffness, 62% pain and 66% fatigue, vs 94, 65, 84 and 84% of patients with RA. MDA criteria were not met by 64% of control subjects for painful joints, 38% for pain, 45% for global health and 18% for HAQ, vs 89, 60, 69 and 52% of RA patients. The four ACR remission criteria were met by only 15% of control subjects over age 50 and 3% of RA patients, and MDA criteria by 28% of controls and 7% of patients.

Conclusions. The majority of community population over age 50 did not meet criteria for remission or MDA in RA. Although a self-report format may differ from results involving an assessor, the current criteria may not be accurate to identify remission or MDA in people with RA who are older than age 50.

KEY WORDS: Rheumatoid arthritis, Remission criteria, Minimal disease activity, Population


   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Remission is a contemporary goal in treatment of patients with rheumatoid arthritis (RA) [1–3]. Remission is clearly present when a patient has no signs of inflammatory activity and no progression of radiographic damage. However, there is no general consensus regarding a definition of remission in RA [4]. Results differed considerably when three assessments of remission were applied to analysis of a cohort of patients with early RA examined 5 yrs after diagnosis: remission was seen in 17% according to American College of Rheumatology (ACR) remission criteria [5], 35% according to ‘clinical remission’ criteria and 58% according to radiographic remission [6]. Furthermore, varying levels of Disease Activity Score 28 (DAS28) have been suggested to identify remission [7].

The ACR remission criteria [5] are the most stringent and widely reported criteria for remission of RA. These criteria include meeting five of six signs or symptoms in two consecutive months: no swollen or tender/painful joints, normal erythrocyte sedimentation rate (ESR) and no morning stiffness, pain and fatigue (Table 1). A need for less stringent criteria for clinical trials led to an outcome measures in rheumatology (OMERACT) definition of minimal disease activity (MDA) which is met by meeting five of seven criteria: pain (0–10) ≤2; swollen joint count (0–28) ≤1; tender joint count (0–28) ≤1; Health Assessment Questionnaire (HAQ, 0–3) ≤0.5; physician global assessment of disease activity (0–10) ≤1.5; patient global assessment of disease activity (0–10) ≤2; and ESR ≤20 [8].


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  		TABLE 1. ACR criteria for remission and OMERACT criteria for MDA

 
The ACR and MDA criteria have not been examined in a control population to determine how frequently they may or may not be met by individuals who do not have RA. The signs and symptoms in these criteria may be common in older people. Although both ACR and OMERACT criteria were designed to be assessed primarily by a health professional, most require querying the patient about joint pain or tenderness, morning stiffness, pain, fatigue and patient global assessment. An HAQ and self-report of the data may approximate data derived by a health professional.

These considerations led us to analyse a cohort of individuals over age 50, who were selected randomly as an age- and sex-matched control group for patients with RA. The proportions who met or did not meet the four ACR remission criteria of no joint pain/tenderness, no morning stiffness, no pain and no fatigue on a mailed self-report questionnaire, and who met or did not meet four MDA criteria concerning joint tenderness, pain, patient global assessment and the HAQ were calculated. Although the findings might not be identical to those obtained by a health professional, the results appear relevant to further studies of remission in RA.


   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Acknowledgements
 References
 
Patients with RA
The Central Finland RA Database includes demographic and clinical data on all patients with RA who have been seen since 1993 in Jyväskylä Central Hospital, which is the only rheumatology clinic in the district serving a population of 267 182 (in 2004). Since 1998, all patients with RA have been monitored using annual mailed questionnaires [9].

Community control subjects
In 2000, a control group of 2000 age- and sex-matched people from the general population was established. The sample was drawn from the Finnish Population Registry, with the permission of the Ministry of Social Affairs and Health. The population sample was designed to be matched to the RA patient group according to age and sex, with a mean age of 55 yrs and to include 70% women, but was otherwise randomly selected. All subjects in the control group were living in the Central Finland District in 2000.

Study design
An identical self-report questionnaire was mailed to community control subjects and to patients with RA in July 2005 and included HAQ for functional status [10, 11], self-report of pain or tenderness of specific joints in a RA disease activity index (RADAI) format [12] and duration of morning stiffness. The RADAI queries current joint pain/tenderness in the fingers, wrists, elbows, shoulders, hips, knees, ankles and toes. Pain, fatigue and global assessment of health were queried on a gradual rating scale including 21 circles/boxes mimicking a 0–10 cm visual analog scale (VAS). The study was approved by the Ethics Committee of Jyväskylä Central Hospital, and Population Register Centre of Finland.

The ACR and MDA criteria
The ACR criterion of ‘no tender joints’ was defined as 0 tender joints on the RADAI format (Table 1). The criterion of ‘no morning stiffness’ was defined as ≤15 min. Values for no pain and fatigue were defined as ≤1 on a scale of 0–10 (Table 1). Results for each of these four ACR criteria and a composite of the four criteria are presented for each of the age- and sex-stratified groups of control subjects and patients with RA. Similar analyses were performed for the MDA criteria of tender joint count ≤1; pain ≤2; patient global assessment ≤2; and HAQ ≤0.5 (Table 1).


   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Acknowledgements
 References
 
Subjects
After one reminder, 3105 of 3839 (80.3%) subjects responded to the questionnaire, including 1705 of 2022 patients with RA and 1400 of 1817 control subjects. The present analyses include those who are ≤50 yrs old: 1034 females with RA and 696 female control subjects, and 405 males with RA and 260 male control subjects.

ACR criteria for remission
Pain in at least one joint was reported by 76% of control subjects over age 50 and 94% of patients with RA (Table 2). Morning stiffness >15 min was reported by 37% of control subjects and by 65% of patients with RA. Pain >1/10 was reported by 62% of control subjects vs 84% of patients with RA. Fatigue >1/10 was reported by 66% of control subjects and 84% of patients with RA.


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  		TABLE 2. Percent of individuals in general population and patients with RA who do not meet ACR remission criteria

 
Only 15% of control subjects, including 14% of women and 19% of men, met the four ACR remission criteria. Even in the youngest age group (50–59 yrs) only 17% of women and 23% of men met the four criteria (Table 2). In the RA population, <5% of all patients met the four ACR remission criteria. If all subjects had no swollen joints and a normal laboratory test, only 30% of individuals over age 50 in the general population and 10% RA patients would meet five of six ACR remission criteria in this survey.

OMERACT criteria for MDA
Pain in more than one joint was reported by 64% of control subjects over age 50 and 89% of patients with RA (Table 3). Pain scores >2/10 were reported by 38% of control subjects and by 60% of patients with RA. Global health estimates >2/10 were reported by 45% of control subjects and by 69% of patients with RA. HAQ functional status scores >0.5 were reported by 18% of control subjects and 52% of patients with RA. The four MDA criteria were met by only 28% of control subjects and 7% of patients with RA (Table 3). If all other criteria were met, including ESR ≤20, swollen joint count ≤1 and physician global assessment of disease activity ≤1.5, 5/7 MDA criteria were met by 68% of control subjects and 38% of patients.


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  		TABLE 3. Percent of individuals in general population and patients with RA who do not meet OMERACT criteria for MDA

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Acknowledgements
 References
 
The primary observation reported here is that the majority of a community control cohort over age 50 did not meet the ACR criteria for remission of RA or the OMERACT criteria for MDA. Indeed, ‘remission rates’ in the elderly population appear to be comparable with those seen in reported cohorts of patients with RA [6, 13–19]. For example, the ACR remission rate was 17% in the early RA study (ERAS) at 5 yrs [18], 18% in the Lund cohort at 10 yrs [19] and 17% in the Jyvaskyla early RA cohort at 5 yrs [6]. In the FIN-RACo trial, in which treatments were adjusted during the trial to reach remission as the treatment goal, the ACR remission rate was 37% in the combination group vs 18% in the monotherapy group [20].

The ACR criteria for remission of RA were developed in the late 1970s and included patients whose mean age was 43 yrs at the time of the diagnosis with a mean disease duration of 9 yrs at the time of the evaluation, i.e. these were relatively young patients [5]. In patients who had a complete remission according to the rheumatologists in the ACR data set, 96% had no morning stiffness, 87% had no fatigue, 85% had no joint pain and 89% had no tenderness/pain on motion, assessed by the investigator [5].

Most patients with RA at this time are older than 50 yrs. For example, in the Central Finland RA database, 82% of women and 86% of men were ≥50 yrs old in July 2005 when they were mailed the questionnaire. The average age to be diagnosed with RA is almost 60 yrs, and it has been increasing over the past decades [21]. The results reported here suggest that ACR remission criteria may not be appropriate to identify remission in people who are >50 yrs old.

A golden standard for remission or MDA of RA does not exist. The ACR and MDA criteria include both assessor (traditionally: objective) and patient-report (traditionally: subjective) variables as well as ESR. It has been shown that ‘subjective’ [22, 23] patient-report variables do not improve with a placebo treatment in clinical trials such as ‘objective’ joint counts, which gives a reason to ask which measures are objective. However, patient-report measures are strongly associated with age [24], muscle strength and sex [25], which should be taken into account when these measures are used in criteria that are applied in all age groups. On the other hand, in 107 RA patients who were judged to be in clinical remission by the treating rheumatologists, almost 50% had progression in their hand/wrist magnetic resonance images (MRI) over 12 months [26] which indicates that an ‘objective’ clinical examination is not accurate enough either to assess remission in RA.

A limitation of the present study is that the results were obtained by self-report rather than investigator assessment such as the ACR criteria. Identification of the presence of morning stiffness, pain and fatigue in an interview, and assessment of joint tenderness by a health professional might have resulted in a lower prevalence of positive findings, but likely not substantially different in control subjects vs patients. A second limitation is that the 2-month ACR time criterion could not be analysed in this survey. However, the requirement of meeting remission criteria for two consecutive months would mean that a lower proportion of individuals would meet remission criteria. A third limitation is that only four remission criteria could be evaluated—not including joint swelling and a laboratory test. However, even if all subjects had no swollen joints and a normal laboratory test, only 30% of individuals over age 50 in the general population and 10% RA patients met five of six ACR remission criteria in this survey. Furthermore, the control population did not consist of healthy individuals but a random sample from a general population with any health conditions except RA; e.g. 28% of female controls and 34% of female patients reported osteoarthritis, percentages were 20 vs 28% in male (P > 0.05, adjusted for age). Nonetheless, these observations might be considered in analyses of criteria for remission or MDA.

We conclude that the majority of a community control cohort ≥50 yrs old did not meet the ACR criteria for remission or OMERACT criteria for MDA of RA. These criteria may not be accurate to identify remission in RA in people over age 50. The findings suggest that criteria for MDA or remission, or inclusion criteria for clinical trials [16, 27], might be based on empirical data rather than a consensus of expert opinions.

Formula


   Acknowledgements
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
References
 
Ms Veronica Goodin for editorial assistance.

The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 

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Submitted 8 November 2006; revised version accepted 7 February 2007.
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