Abstract
Objective To investigate the course of disability related to the upper extremities (UEs) in early rheumatoid arthritis (RA), and to assess correlations between such disability and clinical variables, including grip force.
Methods In an inception cohort of patients with early RA (diagnosed 1995-2005, N = 222, follow-up 10 yrs), disability of the UEs was assessed using a subscore of the Health Assessment Questionnaire–Disability Index (HAQ-DI-UE), and average grip force of the dominant hand was measured. Changes between consecutive follow-up visits in the HAQ-DI-UE subscore, and correlations at each visit with key clinical variables, were assessed. The relation between joint involvement and HAQ-DI-UE was examined using multivariate linear regression analysis.
Results The HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up (mean change −0.26, 95% CI −0.18 to −0.34), and increased significantly after 2 years. There were fairly strong correlations for HAQ-DI-UE with grip force (r = −0.50 to −0.62), patient global assessment (r = 0.53 to 0.64), and patient-reported pain (r = 0.54 to 0.60) at all timepoints through 5 years, but only moderate to weak correlations with swollen joints, C-reactive protein, and erythrocyte sedimentation rate. At inclusion, wrist synovitis and tender proximal interphalangeal joints both had an independent effect on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had a greater importance at 6 months.
Conclusion Disability related to the UEs decreased significantly during the first 6 months, and increased again after 2 years. The correlations with clinical variables underline the major effect of pain and impaired hand function in early RA.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is often associated with disability.1 RA usually involves the distal upper extremity (UE) joints, and > 80% of patients have dysfunction in their hands.2 Synovitis of the wrist joint3 and of the first metacarpophalangeal (MCP) joint are the main contributors to reducing grip force in patients with early RA.4 MCP IV synovitis also has a substantial effect on grip force.4 Patients with RA have been shown to have reduced grip force in comparison with age- and sex-matched healthy populations.5 Reduced hand function contributes to impairment of activities of daily life (ADLs), particularly in manual performance that requires some grip force.6 We have previously reported improvement in age- and sex-standardized grip force in early RA, in particular during the first year after diagnosis.5 However, grip force remained significantly reduced compared to the general population, even in patients in clinical remission.5
In rheumatological care, patient-reported outcome measures (PROMs) are used for the purpose of assessing the severity of RA, including disability.7-9 One of the most commonly used instruments to measure disability in RA is the Health Assessment Questionnaire–Disability Index (HAQ-DI).10-13 PROMs (eg, HAQ) and RA disease activity measures (eg, Disease Activity Score in 28 joints [DAS28]) have been found to be moderately correlated.14 A moderate association has also been found between HAQ-DI and grip force in patients with RA.15 Therefore, it is important to study the course of disability as a separate outcome in RA.9
HAQ-DI is a general measure of disability11 and only a subset of the questions is related to ADLs that are affected by hand function. Pain and a limited range of movements of joints have the greatest effect on individual subdimensions of the HAQ-DI.16 Studies have shown that higher HAQ-DI scores at baseline are associated with long-term disability,17,18 especially for women, older patients, and those with high pain scores.18 Decreased grip force, a large number of swollen and tender joints in the UEs, and limitations in wrist and shoulder motion were related to many of the subdimensions and explained increased disability with higher HAQ scores.16,19 Previous studies have addressed the HAQ overall or individual subdimensions, and not dimensions reflecting disability related to the UEs.
The objective of this study was to specifically investigate the course of disability related to the UEs in early RA using a subset of the HAQ-DI (HAQ-DI-UE), and to assess relations between HAQ-DI-UE and clinical variables. Further, correlations between HAQ-DI-UE and grip force were studied.
METHODS
Patients. An inception cohort of patients with early RA (symptom duration ≤ 12 months), recruited in 1995-2005, was investigated. The patients were diagnosed with RA by a rheumatologist and fulfilled the 1987 American College of Rheumatology classification criteria for RA.20 The study included individuals from a defined area: the city of Malmö, Sweden (population 260,000 in 2000). Patients were recruited from the rheumatology outpatient clinic of Malmö University Hospital, which was the only hospital serving the city, and from the 4 rheumatologists in private practice in Malmö. All procedures were in accordance with the ethical standards of the regional research ethics committee and with the 1964 Declaration of Helsinki and its later amendments. All patients gave their written informed consent to participate, and the study was approved by the regional ethical review board for southern Sweden (Lund, Sweden, LU 410-94 [January 30, 1995] and LU 311-02 [June 10, 2002]).
Clinical assessment. Patients were managed according to usual care, with no prespecified protocol for pharmacotherapy or rehabilitation. The patients were included before the current practice of treat-to-target21 was implemented, and before early treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) came into widespread use.
In a structured follow-up program, all patients were examined by the same rheumatologist. Visits were scheduled at 6, 12, and 24 months, as well as 5 years and 10 years after inclusion. Using a standardized clinical examination protocol, individual joints were assessed as swollen/not swollen and tender/not tender, and standard swollen joint counts of 28 joints (SJC28) and tender joint counts of 28 joints (TJC28) were obtained. Disability was assessed using the HAQ-DI.10 The Swedish-validated translated version of the HAQ-DI22 was used. Patient-reported pain and patient global assessment (PtGA) of disease activity were assessed using visual analog scales (VAS; scale 0-100). Information on treatment, including DMARDs, was obtained through structured interviews as previously described.5 Data on treatment with bDMARDs during the study period were obtained through linkage to a regional biologics register.23 Most patients were started on a DMARD at the time of diagnosis. The use of methotrexate (MTX) as a first choice increased gradually during the study period. A limited number of patients with severe, refractory disease were treated with bDMARDs after their introduction in 1999. Blood samples were obtained at the visit when the joint assessment was performed (within 1 hour). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were analyzed using standard methods at the Department of Clinical Chemistry, Malmö University Hospital.
Assessment of grip force. Grip force (Newtons) was measured using the electronic instrument Grippit (AB Detektor). This was performed at the same visit as the joint assessment (within 1 hour). The patient was seated comfortably in a chair without armrests, with the shoulder, arm, and hand in standard positions as previously described.24 The other arm was resting on the table. Standardized instructions were given. When using this procedure, the test-retest scores for Grippit measures have been demonstrated to be high.24 Average values of the 10-second uninterrupted grip were obtained, as previously described.5 Average grip force values of the dominant hand at inclusion and at the 6-month, and 1-, 2-, 5-, and 10-year follow-up visits were compared to the expected, based on age- and sex-specific reference values from a convenience sample from a cross-sectional study of volunteers in the region of Oslo, Norway.25 Grip force values for each patient were expressed as percent of the expected, based on the reference values.
Disability related to the UEs. To estimate disability based on self-reported activity limitations during the study period, we used the validated Swedish version22 of the HAQ.10 This assessment instrument included 20 questions divided into 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other usual activities, and is used in practice to calculate the HAQ-DI (range 0-3). In previous studies, subscore for lower extremities (LEs), which included 10 questions that cover activities that are mainly dependent on function of the LEs, has been calculated (HAQ-DI-LE).26-28 To more specifically address disability of the UEs, we computed a subscore, HAQ-DI-UE, which includes the remaining 10 questions on activities mainly performed using the UEs (Supplementary Table S1, available with the online version of this article).
Statistics. Changes in HAQ-DI-UE between 2 consecutive follow-up visits were assessed using the paired samples t test. Correlations between HAQ-DI-UE and key clinical disease variables (ie, grip force, ESR, CRP, VAS for PtGA [VAS global] and pain [VAS pain], and SJC28 and TJC28) at each visit were assessed using the Spearman rank test. Further, the distributions of HAQ-DI-UE at different timepoints in patients with and without current swelling, and with and without tenderness of ≥ 1 joint in each joint group (ie, shoulders, elbows, wrists, and MCP and proximal interphalangeal [PIP] joints) were compared using the Mann-Whitney U test. Linear regression analysis was used to further assess the relation between joint involvement (as discussed above) and HAQ-DI-UE at inclusion and 6 months of follow-up. Normality of distribution for the residuals was examined using the Shapiro-Wilk test. Covariates with P values < 0.10 in the bivariate models were included in multivariate models. Collinearity between covariates was examined using the Spearman test. In cases of major collinearity, the covariate with the strongest association with the dependent variable was selected for the multivariate analysis.
RESULTS
Patients. Two hundred twenty-two patients with early RA (71% women, mean age 60.8 years, median symptom duration 7 months) were investigated (Table 1). At inclusion, the mean DAS28 was 4.6 (SD 1.4), and the median HAQ-DI was 0.75 (IQR 0.38-1.25). Most patients were treated with MTX at inclusion or later (Table 1). The mean average grip force of the dominant hand increased from 40% of the expected at inclusion to 66% of the expected at 10 years. Data on both HAQ-DI-UE and average grip force of the dominant hand were available for 222 patients at inclusion, 207 patients at 6 months, 209 at 1 year, 200 at 2 years, 167 at 5 years, and 110 at 10 years (Table 1).
Characteristics of the patients with early RA with data on HAQ-DI-UE.
Changes in HAQ-DI-UE in early RA over time. In the paired analysis of patients with data available at both timepoints, there was a significant decrease in HAQ-DI-UE from inclusion to the 6-month follow-up (median HAQ-DI-UE 0.80 [IQR 0.40-1.20] vs 0.60 [IQR 0.00-1.00]; Figure 1). The mean change in HAQ-DI-UE between inclusion to the 6-month follow-up was −0.26 (95% CI −0.18 to −0.34). HAQ-DI-UE levels were stable between 6 months and 2 years, whereas between 2 years and 5 years, there was a significant increase (from 0.40 [IQR 0.00-1.00] to 0.60 [IQR 0.20-1.00]). The mean change in HAQ-DI-UE between 2 years and 5 years was 0.10 (95% CI 0.03-0.17). In the limited subset with data available at 10 years, there was also a trend toward an increase in HAQ-DI-UE compared to the 5-year visit (Figure 1).
Changes in HAQ-DI-UE between visits; patients with data at both timepoints. Paired t tests. Boxes indicate medians and quartiles, whiskers indicate the 95% highest and lowest percentiles within nonoutlier range. HAQ-DI-UE: Health Assessment Questionnaire–Disability Index, upper extremities.
Correlations for clinical variables with HAQ-DI-UE. There were strong correlations for HAQ-DI-UE with grip force, VAS global, and VAS pain at all timepoints, and moderate to weak correlations with SJC28, TJC28, ESR, and CRP (Figure 2 and Figure 3; Supplementary Table S2, available with the online version of this article). HAQ-DI-UE correlated significantly with grip force at inclusion (r = −0.62; P < 0.001; Figure 2A), and at all other timepoints (Supplementary Table S2). Similar correlations were noted for both VAS global (Figure 2C and Figure 3C; Supplementary Table S2) and VAS pain (Figure 2D and Figure 3D; Supplementary Table S2).
Correlations for clinical variables with HAQ-DI-UE at inclusion using Spearman test. (A) Grip force (r = −0.62; P < 0.001). (B) ESR (r = 0.33; P < 0.001). (C) VAS global (r = 0.53; P < 0.001). (D) VAS pain (r = 0.58; P < 0.001). (E) Swollen joint count (score 0-28, r = 0.39; P < 0.001. (F) Tender joint count (score 0-28; r = 0.50; P < 0.001). ESR: erythrocyte sedimentation rate; HAQ-DI-UE: Health Assessment Questionnaire–Disability Index, upper extremities; VAS: visual analog scale.
Correlations for clinical variables with HAQ-DI-UE at 10 years using Spearman test. (A) Grip force (r = −0.45; P < 0.001). (B) ESR (r = 0.09; P = 0.35). (C) VAS global (r = 0.44; P < 0.001). (D) VAS pain (r = 0.36; P < 0.001). (E) Swollen joint count (score 0-28, r = 0; P = 0.99). (F) Tender joint count (score 0-28; r = 0.26; P < 0.01). ESR: erythrocyte sedimentation rate; HAQ-DI-UE: Health Assessment Questionnaire–Disability Index, upper extremities; VAS: visual analog scale.
Relation between joint involvement and HAQ-DI-UE. Among patients with data on HAQ-DI at inclusion, 192 patients had swelling of > 1 MCP joint in the UE, whereas swollen wrists, PIP, elbows, and shoulders were observed in 153, 139, 20, and 19 patients, respectively. Whereas tenderness at inclusion was more common compared to clinical synovitis in the shoulders (n = 77) and elbows (n = 34), the reverse was the case for MCP joints, wrists, and PIP joints, where tenderness was observed in 136, 118, and 119 patients, respectively.
Proportions with current joint involvement decreased somewhat over time, in particular those with swollen and tender PIP joints (Supplementary Table S3 and S4, available with the online version of this article). Overall, there was a greater reduction in tenderness of different joints in the UEs from inclusion until 10 years of follow-up, compared to the reduction in joint swelling (Supplementary Table S3 and S4).
At inclusion, higher HAQ-DI-UE scores were found in those with current clinical wrist synovitis, clinical MCP synovitis, and clinical shoulder synovitis, compared to those without such joint involvement (Figure 4A). There were also significant associations between tenderness of elbows, wrists, and MCP and PIP joints with higher HAQ-DI-UE (Figure 4B).
HAQ-DI-UE at inclusion, by presence of joint involvement in the UEs. (A) Swollen joints, present (+) vs absent (−). Circles indicate medians, whiskers indicate IQRs. Shoulder: P = 0.03; elbow: P = 0.99; wrist: P < 0.001; MCP: P < 0.01; PIP: P = 0.08. (B) Tender joints, present (+) vs absent (−). Circles indicate medians, whiskers indicate IQRs. Shoulder: P = 0.08; elbow: P < 0.01; wrist: P < 0.001; MCP: P < 0.001; PIP: P < 0.001. HAQ-DI-UE: Health Assessment Questionnaire–Disability Index, upper extremities; MCP: metacarpophalangeal; PIP: proximal interphalangeal; UE: upper extremities.
Patients with clinical wrist synovitis had significantly higher HAQ-DI-UE scores at 6 months, 1 year, and 5 years, but not at 2 years and 10 years (Supplementary Table S3, available with the online version of this article). Higher HAQ-DI-UE was associated with tenderness in wrists and elbows at all timepoints from inclusion to 10 years of follow-up, in MCP and PIP joints through 5 years, and in shoulders from 6 months to 10 years (Supplementary Table S4).
Joint involvement and disability related to UEs: multivariate analyses. In bivariate and multivariate linear regression models on the relation between joint involvement and HAQ-DI-UE at inclusion and after 6 months, the residuals were normally distributed (Shapiro-Wilk statistic > 0.90). Models including data at other timepoints did not fulfill normality of distribution for the residuals. Results of the linear regression analyses at inclusion and at 6 months are shown in Table 2. In multivariate analysis, there was a significant association between clinical wrist synovitis and higher HAQ-DI-UE at inclusion (β 0.37, 95% CI 0.20-0.54) but not at 6 months (Table 2). The presence of PIP tenderness was associated with higher HAQ-DI-UE at inclusion, independent of other joint involvement (Table 2). At 6 months of follow-up, PIP joint swelling (β 0.22, 95% CI 0.07-0.36), tender shoulder (β 0.28, 95% CI 0.12-0.44), and tender wrist (β 0.30, 95% CI 0.12-0.47) were all associated with higher HAQ-DI-UE in multivariate analysis (Table 2).
Relation between joint involvement and HAQ-DI-UE at inclusion and 6 months (linear regression).
DISCUSSION
In this study of patients with early RA, the HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up. HAQ-DI-UE levels were stable between 6 months and 2 years, whereas between 2 years and 5 years, there was a significant increase. Further, there were strong correlations for HAQ-DI-UE with grip force and PROMs at all timepoints, and moderate to weak correlations with joint counts and laboratory variables of inflammation. The strong and consistent negative association between grip force and disability related to the UEs underlines the importance of the grip in this context.
Involvement of several joint groups contributed to disability related to the UEs. At inclusion, wrist synovitis and tender PIP joints both had an independent effect on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had greater importance at 6 months.
Our results suggest that patients with poor PROMs in early RA are at increased risk of persistent limitations in ADLs that are performed using the UEs. Other studies have shown that patients with early RA have a highly variable health status, and even among those who indicate that they are in an acceptable symptom state (when specifically asked about this), PROMs are important for the future prognosis.29
Previous studies have investigated disability overall and not HAQ-DI-UE specifically. Disease activity, measured as swollen and tender joint counts, as well as pain, have both been shown to be associated with the total HAQ-DI score.30 Several other studies demonstrated similar results, with associations between high disease activity and impaired PROMs like the HAQ.14,31-33
One of these studies compared 2 large inception cohorts of patients with early RA, the Early Rheumatoid Arthritis Study (inclusion period 1986-1997) and the Norfolk Arthritis Register (1990-1994), both from the United Kingdom.31 Both studies analyzed trajectories (ie, patterns of progression of disability).31 The overall pattern over time for HAQ-DI was similar to our observations with HAQ-DI-UE. They also reported an association with DAS2831 but did not investigate the importance of the subcomponents (swollen and tender joints, ESR, VAS pain, and VAS global), in contrast with our study.
In a study based on the Canadian Early Arthritis Cohort, the HAQ-DI and DAS28 decreased significantly over time from baseline to 24 months,32 but no further follow-up was reported. The Swedish Early Interventions in Rheumatoid Arthritis (TIRA) study group reported that disability decreased significantly during the first year after inclusion in their inception cohort.1 This was followed by gradual worsening of disability up to the 8-year follow-up.1 In that study, grip force and pain intensity were major contributors to disability measured using HAQ-DI,1 similar to our findings with HAQ-DI-UE. Taken together, these studies suggest that although disability may decrease in early RA, subsequent worsening of disability is common both for disability overall and specifically for the UEs, in particular in those with persistent problems with active disease and severe pain.1,31,32
In a study of early RA, performed by the Swedish Better Anti-Rheumatic Farmacotherapy (BARFOT) group, outcomes including the DAS, VAS pain, PtGA, and HAQ-DI were followed for 5 years.33 Interestingly, patterns were similar in patients diagnosed in 1992-1999 and 2000-2006, with no difference in VAS pain or HAQ-DI between the groups, despite the fact that the latter group was more actively treated.33 The authors suggest that mechanisms other than inflammation might be of importance for persistent disability and pain.33 This is in accordance with the results of the present study, with limited correlation between HAQ-DI-UE and markers of inflammation, in particular with long-term follow-up.
The major effect of reduced grip force on disability has been demonstrated in several previous studies,1,2,15,16,30 including a survey of the cohort investigated in the present study.5 This suggests that hand training could be beneficial in early RA. Indeed, structured rehabilitation, including a tailored exercise program for the distal UEs, has been shown to improve the grip strength and reduce the effect of the disease on the individual.34 Further, multidisciplinary interventions may prevent progressive disability in RA.1,34-36 The utility of HAQ-DI-UE for selecting patients for specific rehabilitation programs and/or intensified pharmacotherapy, and the responsiveness of HAQ-DI-UE to such interventions, should be further studied.
Our results also showed a variable strength of association between joint involvement and disability related to the UEs, which may be partly explained by the prevalence of involvement of individual joints. As in the present cohort, a Japanese study of 3457 patients with established RA that analyzed the importance of change in joint involvement over time found that involvement of wrist and shoulder joints contributed significantly to worse HAQ scores in patients with RA, whereas for the small joints in the hand (MCP and PIP), the effect was modest.19 In our study, there was a greater importance for PIP joint involvement, which may characterize early RA. Impairment of small joints could influence particular subdimensions of the HAQ score,19 which might explain our finding.
In a large cohort of 4530 German patients with established RA, the most frequently affected joint was shown to be the wrist (45.5%).37 Together with shoulders and elbows, wrist joints have been shown to account for the greatest contributions to disease activity, HAQ-DI, and long-term functional prognosis.38 Several other studies demonstrated a major effect of wrist involvement on grip force in RA.3,16
A limitation of the study is that the HAQ-DI-UE subscore of the HAQ-DI has not been studied before, and is not a validated outcome measure. A corresponding subscore for the LEs (HAQ-DI-LE), which has been used in previous studies,26-28 included 10 questions covering activities that are mainly dependent on the function of the LEs. Because of the heterogeneity of RA and the differential effect on various joints in individual patients, there is a rationale for constructing separate questionnaires, sorting the 20 subdimensions into 2 groups: 1 for the LEs and 1 for the UEs. Further studies should evaluate the utility of this approach.
Another limitation in the present study is related to the loss of patients that were not assessed at all follow-up visits. This may lead to underestimation of long-term disability in RA. However, changes over time were assessed using paired analyses of patients with data at 2 consecutive visits. Further, because of the limited sample size, some factors that contribute to higher HAQ-DI-UE may not have been identified in this study.
Finally, patients in this study were diagnosed during 1995-2005, and pharmacotherapy, including bDMARDs, was not as aggressive during the earlier part of the follow-up as would be expected in a current inception cohort. In general, outcomes in patients with RA have improved substantially in more recent years. This may reduce the relevance of the observations to current times.
Strengths of this study include the structured longitudinal follow-up of an inception cohort from a defined catchment area. Therefore, selection bias is not a major issue in this study, and the results could be generalized to patients with RA seen in clinical practice. On the other hand, the results may not apply to other ethnic or geographic settings, or patients managed using completely different strategies for pharmacologic treatment and rehabilitation. The joint assessments performed by the same rheumatologist, and structured assessment of PROMs including the widely used HAQ-DI at all follow-up visits, are further strengths of the study.
In conclusion, in this study of patients with early RA, disability related to the UEs decreased significantly from inclusion to the 6-month follow-up, and increased significantly again after 2 years. HAQ-DI-UE scores correlated strongly with grip force and PROMs at all timepoints, and to a lesser extent, with joint counts and laboratory markers of inflammation. The results underline the major effect of pain and reduced grip strength in early RA.
ACKNOWLEDGMENT
In remembrance of Christina Book, MD, PhD, who initiated this project and performed a major part of the data collection. She passed away before preparation of this manuscript. The authors would like to thank Ingegerd Wikström, OT, PhD, for her contribution to collection of the data, including grip strength assessment.
Footnotes
CONTRIBUTIONS
All the authors have seen and approved the final version. All the authors meet the Uniform Requirements for Manuscripts Submitted to Biomedical Journals criteria for authorship.
FUNDING
This work was supported by the Swedish Research Council (grant number 2015-02228), Swedish Rheumatism Association (grant number R-664091), and Lund University (grant number ALFSKANE-446501).
COMPETING INTERESTS
The authors declare no conflicts of interest relevant to this article.
- Accepted for publication October 3, 2024.
- Copyright © 2025 by the Journal of Rheumatology
REFERENCES
DATA AVAILABILITY
The datasets generated and/or analyzed during the current study are not publicly available because of Swedish legislation (the General Data Protection Regulation), but a limited and fully anonymized dataset containing the individual patient data that support the main analyses is available from the corresponding author on reasonable request.
SUPPLEMENTARY DATA
Supplementary material accompanies the online version of this article.
