Life expectancies of Japanese patients with rheumatoid arthritis: a review of deaths over a 20-year period

Abstract

We investigated trends in life expectancy in rheumatoid arthritis (RA) patients, reviewing records for 286 patients (204 female, 82 male) who had died over the past 20 years. The average age at death was 68.8 years before 1990, increasing to 72.1 years after 2001. Trends in disease modifying anti-rheumatic drugs (DMARDs) saw gold preparations (45.2%) predominate before 1990, sulphydryl donor agents (53.6%) from 1991 to 2000, then methotrexate (43.0%) after 2001. The most common causes of death were infectious diseases up to 1995, rheumatic disease 1996–2000, and cardiovascular events and malignancies after 2001. Major advances in surgical interventions, such as joint replacement surgery, occurred after 1990. Surgical intervention followed by a period of rehabilitation maintained a favourable level of activities of daily living (ADLs), The requirements for favourable life expectancy are control of RA inflammation and maintenance of a favourable level of ADLs. Although recently developed DMARDs and biological agents show promise, caution is required to avoid serious adverse reactions. Optimum care of patients with RA will require preventive measures and early intervention for infections and rheumatic diseases, as well as for lifestyle diseases, osteoporosis and malignancies.     

Predictors of hand function in patients with rheumatoid arthritis

Objectives. The aims of this study were to determine: (1) what factors predict patient self-estimated hand function; (2) what factors predict actual hand function; and (3) the relationship among actual hand function, patient estimates of hand function, and self-assessed activities of daily living (ADL). Methods. Fifty-two patients with rheumatoid arthritis completed wrist and hand mobility measures, grip strength, pain, stiffness, and estimated hand function tests, along with the Sollerman Grip Function Test (actual hand function), Health Assessment Questionnaire (HAQ), and subscales of the Arthritis Impact Measurement Scales (AIMS). Results. Grip strength and stiffness were the strongest predictors of self-estimated hand function. Flexion and extension deficits in digits II through V were the strongest predictors of actual hand function. Actual hand function and self-estimated hand function were significantly correlated with each other and with the HAQ and AIMS subscales. Conclusions. Measures of deficit are the most useful in predicting actual hand function, whereas measures of strength and flexibility are most useful for estimated hand function.     

Evaluation of the Jebson hand function test for use in patients with rheumatoid arthritis

Purpose. We have evaluated the Jebson hand function (JHF) test for use in patients with rheumatoid arthritis (RA). Methods. The JHF test was administered to 25 patients with RA. Results were compared to normative data and related to ability to perform activities of daily living (ADL), pain, and deformity. Results. The JHF test detects differences between patients with RA and normals; all components except for writing show correlations with ADL and deformity. There were no significant correlations with pain. Conclusions. The JHF test is a useful adjunct to evaluation of the hand in RA.     

Associations between walking time,quadriceps muscle strength and cardiovascular capacity in patients with rheumatoid arthritis and ankylosing spondylitis

The aim of this study was to examine whether there are any associations between walking time, quadriceps muscle strength and cardiovascular capacity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Thirty-one patients with RA and 26 patients with AS belonging to Steinbrockers functional class I-II were examined. Cardiovascular capacity was calculated from the expired air during a bicycle test and quadriceps muscle strength by the peak torque from an isokinetic dynamometer test. Walking time was the time it took to walk a distance of 160 m on a flat floor and to climb up and down a staircase. In patients with RA, flat floor walking and stair climbing times correlated inversely with quadriceps muscle strength and cardiovascular capacity. Similar results were seen in patients with AS, although the association between cardiovascular capacity and stair-climbing time was not statistically significant. Multiple regression analysis was performed for all patients with quadriceps muscle strength and cardiovascular capacity applied as independent variables in two separate models. Cardiovascular capacity explained 32% and quadriceps muscle strength 21% of the variance in flat floor walking time. Quadriceps muscle strength, together with diagnosis and age, explained 38% of the variance in stair-climbing time, and cardiovascular capacity together with age and pain explained 36% of the variance. In conclusion, in spite of cardiovascular capacity and quadriceps muscle strength being associated with walking times, the findings suggest that they play only a modest role in explaining rapid walking on flat floor and in stairs.Abbreviations AS Ankylosing spondylitis - RA Rheumatoid arthritis - VAS Visual analog scale     

Causes of death in patients with rheumatoid arthritis autopsied during a 40-year period

We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized.     

Long-term methotrexate (MTX) combination therapy versus MTX alone for active rheumatoid arthritis

In 37 patients with active rheumatoid arthritis (RA) responding insufficiently to a diseasemodifying anti-rheumatic drug (DMARD), we compared the safety and efficacy of methotrexate (MTX) used alone (MTX-only group) with MTX used in combination (combined-treatment group). Patients were assigned randomly to 5 years of treatment with MTX alone (initial dose, 7.5 mg/week) or with MTX (initial dose, 5 mg/week) plus their previous DMARD continued at half dosage. After 3 years of therapy, the combined-treatment group showed significantly better sustained response of the Lansbury index, erythrocyte sedimentation rate and C-reactive protein than the MTX-only group. Ten patients withdrew because of adverse drug effects, with a somewhat higher frequency in the combined-treatment group (six of 19, 32%) than in the MTX-only group (four of 18,22%) difference not significant). One patient in each group withdrew because of insufficient response to therapy. We found that combining the original drug with MTX in previously intractable RA cases resulted in at least additive efficacy.     

Life activities of persons with rheumatoid arthritis with and without depressive symptoms

Objective. Persons with rheumatoid arthritis (RA) report more activity losses than persons without RA. Persons with RA who report depressive symptoms experience lower levels of functioning. We integrated these findings and examined the association of depressive symptoms with the activities in which persons with RA participate. Methods. We surveyed 726 persons with RA and 192 matched controls. Within each group, we examined the perceived importance and actual performance of 65 life activities by individuals with and without depressive symptoms. Results. Significantly more individuals with RA reported depressive symptoms. Among persons with RA, those who had depressive symptoms performed fewer activities, particularly fewer valued activities. In contrast, among controls, those who were depressed rated fewer activities as important, but exhibited few significant differences in the performance of activities. Conclusions. Depressive symptoms and life activities are associated differently among persons with RA and controls. The higher rate of depression among persons with RA may be partially due to the inability to perform valued activities.     

Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid arthritis

Abstract

Objective. Iguratimod (IGU) is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis (RA). We conducted a 24-week study on the efficacy of IGU in RA patients with daily clinical use.

Methods. Forty-one patients were enrolled in this study, and the improvement in RA was evaluated every 4 weeks during the 24 weeks.

Results. The patient's global assessment of the disease activity with a scale (Pt VAS) was significantly decreased beginning at week 4. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein (CRP), simplified disease activity index and clinical disease activity index all significantly decreased at week 24. The matrix metalloproteinase-3 level was significantly decreased by the combination treatment with methotrexate at week 24. According to a logistic regression analysis, the factor which was most associated with the achievement of low disease activity (DAS28-CRP < 2.7) at week 24 was the DAS28-CRP at week 0.

Conclusions. IGU had significant clinical effects on the RA patients within 24 weeks. IGU might therefore represent a new practical choice to treat RA patients.     

Radiographic progression of large joint damage in patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs

Objectives: Radiographic progression of damage to the small joints in patients with rheumatoid arthritis (RA) is well known; however, it has not been studied fully in the large joints. In this study, we looked at the prevalence of radiographic progression of large joint damage in patients with RA treated with biological disease-modifying anti-rheumatic drugs (bDMARDs).

Methods: A total of 273 large joints in the upper and lower extremities of 67 patients with RA treated with bDMARDs were investigated. Radiographs for tender and/or swollen large joints were taken at least twice during the study period (mean 18.6 months), and the progression of damage was evaluated.

Results: Progressive damage was found in 20.9% of patients and 6.2% of joints. A multivariate analysis revealed that the Larsen grade (LG) alone was a risk factor for progressive damage. The LG cutoff value was determined to be 2.5 (sensitivity: 0.529, specificity: 0.805).

Conclusions: The only factor to predict progressive damage was the LG of the joints with symptoms, and the damage must be stopped within LG II. Regular radiographic examinations for large joints should be performed in addition to routine examinations for small joints, such as the hand and foot.     

Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid arthritis and a literature review

Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study summarizes the findings of eight cases of copresent RA and gout and compares them with 31 pure RA cases. Additional reported cases were retrieved from the current literature by Medline search. Patients with copresent RA and gout were older (p = 0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate crystals, was aspirated most frequently from the knee (five out of eight), followed by the first metatarsophalangeal joint (three out of eight). Serum creatinine and urate levels in the copresent group were significantly higher (p < 0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA. Copresent subjects had much lower percentage of positive rheumatoid factor (RF) tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects, 75% had gouty arthritis before diagnosis of RA, which is consistent with earlier reports. Seven copresent subjects had gout attacks under disease-modifying antirheumatic drug use. This study revealed that polyarthritis negative for RF in a previously gouty patient may be RA and vice versa. This combination occurs more frequently in males. Moreover, anti-CCP antibody examination is not helpful for this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in joints with intense swelling, especially in old RA subjects with renal insufficiency or involvement of lower extremities. Conversely, RA must be considered in gouty patients with polyarticular involvement.     

Antibodies to rheumatoid arthritis nuclear antigen (RANA) in Japanese patients with rheumatoid arthritis

Summary We studied antibodies to rheumatoid arthritis nuclear antigen (RANA) by the Ouchterlony method in 0.5% agarose plates, using soluble antigen extracted with 0.25 M sucrose solution from cultured Raji cells. Anti-RANA antibody was found in sera from 24 to 40 (60%) patients with rheumatoid arthritis (RA), from 4 of 20 (20%) patients with systemic lupus erythematosus (SLE), and from 2 of 30 (7%) healthy controls. When sucrose extracts from BJAB, Ramos, and JM cells were used as the cellular antigens, no anti-RANA precipitin lines were detected. Indirect immunofluorescence study, using Raji cells or human B lymphocytes transformed by EB virus as substrate tissues, demonstrated anti-RANA antibody as fine speckled nuclear staining. Although RA patients with positive anti-RANA antibody usually had high titers of anti-Epstein-Barr nuclear antigen (EBNA) and anti-viral capsid antigen (VCA) IgG antibodies, the Wilcoxon ranks sum test showed no close statistical correlation between the presence of anti-RANA antibodies and the titers of anti-EBNA or anti-VCA (IgG) antibodies. These data showed that the incidence of positivity of anti-RANA antibodies in Japanese RA patients is almost the same as that in American and European RA patients.     

Assessment of serum interleukin-20 level in rheumatoid arthritis patients: Relation to disease activity and ultrasound measures

Aim of the workTo investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings.Patients and methods45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score (DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay.ResultsMean age of patients was 34.5 ± 11 years; 39 females and 6 males and disease duration 15.8 ± 8.3 years. Their mean DAS-28 was 4.1 ± 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1–58.5 ng/l) than in controls 13.1; 11–15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL- 20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001).ConclusionPatients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA.     

Preferences of Japanese rheumatoid arthritis patients in treatment decision-making

Objectives

We investigated the decision-making preferences of rheumatoid arthritis (RA) patients using two different scales: the Decision Making Preference Scale (DMPS) and the modified Control Preference Scale (CPS). In addition, we evaluated the factors associated with patients’ preferences for decision-making.

Methods

A cross-sectional study was performed using a self-administered anonymous questionnaire between October and December 2010 on 406 RA outpatients who consecutively visited 3 hospitals in Japan. The following variables were investigated: (1) DMPS, which is a subscale of the Autonomy Preference Index, composed of six items; patients responded on a 5-point Likert scale. (2) The modified CPS, in which patients were asked to choose one actual and one desired role in decision-making from among three options (passive role, collaborative role, and active role). (3) Sociodemographic data and RA-specific characteristics. Multivariate analyses were used to assess the relationship between patients’ preferences and selected variables.

Results

The response rate was 58.6 %. There were few patients who wished to make their own decisions when they were hospitalized or illness became worse. However, the majority of patients desired to collaborate with the doctor in making treatment decisions according to the results of modified CPS. The results of modified CPS were significantly associated with the total scores of DMPS. Multivariate analysis demonstrated they younger age and not-housewife were associated with high scores of DMPS.

Conclusions

Patient preferences in decision-making vary at RA outpatient clinic. Physicians need to assess decision-making preferences on an individual basis.     

Subclinical entheseal involvement in patients with rheumatoid arthritis

BackgroundEnthesopathy is a common feature of Spondyloarthritis (SpA) but can also be found in rheumatoid Arthritis (RA). Recognizing enthesopathy could be challenging because of low sensitivity and specific clinical testing. To detect enthesopathy, The European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US).Aim of the workTo investigate the frequency and distribution of entheseal involvement in RA patients and its relation to disease activity.Patients and methods100 RA patients with any symptom in foot and ankle were enrolled. Disease activity score (DAS28), Visual analogue scale (VAS), Health assessment questionnaire-Disability index (HAQ-DI) and Glasgow Ultrasound Enthesitis Scoring System (GUESS) were assessed.ResultsThe mean age of patients was 44.1 ± 12.2 years, disease duration was 7 ± 5.8 years and 86% were females. The mean DAS28 score was 4.3 ± 1.2 and GUESS score was 7.2 ± 4.2; all patients had variable degrees of enthesitis: 30% of patients had mild enthesitis, 42% had moderate enthesitis and 28% had marked enthesitis. GUESS was significantly higher in patients with moderate (7.8 ± 4.9) and high (7.2 ± 3.2) disease activity than in patients with low disease activity (5.2 ± 3.9) and those in remission (6.5 ± 1.9) (p = 0.015). HAQ, Age and ESR significantly correlated with GUESS score (r = 0.19, p = 0.049; r = 0.23, p = 0.023; r = 0.33, p = 0.001 respectively).ConclusionSubclinical enthesitis is remarkable in RA patients. Quadriceps tendon enthesis was mostly affected. Enthesitis is significantly related to age, ESR and HAQ. The presence of enthesitis in RA may represent a potential marker for disease activity.     

A comparative evaluation of quality of life and life satisfaction in patients with psoriatic and rheumatoid arthritis

Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have a negative impact on patients’ quality of life (QOL). The aim of this study was to compare QOL and life satisfaction in patients with RA and PsA. Forty patients with PsA, 40 patients with RA, and 40 healthy control subjects were included in the study. Demographic data and clinical characteristics including age, sex, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), peripheral pain assessed by visual analog scale (VAS) and Larsen scores of hand X-rays were recorded. Nottingham Health Profile (NHP) was used to evaluate QOL, and Life satisfaction index (LSI) was used to measure psychological well-being in both groups. The demographic data of the subjects were similar between the groups. The scores of all NHP subscales were significantly higher and the scores of LSI were significantly lower in PsA and RA patients than in control subjects. The inflammation markers including ESR, CRP, pain by VAS and Larsen scores were found to be significantly higher in RA patients. The scores of LSI were similar between the groups. Although the scores of physical domains of NHP (pain and physical disability) were statistically higher in RA patients (p<0.05), the scores of psychosocial subgroups of NHP were similar between RA and PsA patients (p>0.05). Both PsA and RA patients had disturbed QoL and decreased life satisfaction. In conclusion, peripheral joint damage, inflammation, and physical disability are significantly greater in RA but psychosocial reflection of QOL and life satisfaction are the same for both groups which can be explained by the additional impact of skin disease in patients with PsA.     

Nailfold capillaroscopic changes in Egyptian patients with psoriatic arthritis in comparison to rheumatoid arthritis

IntroductionNailfold capillaroscopy (NFC) is simple technique for assessment of the microvascular changes recognized in both diseases can be used in helping the differential diagnosis.Aim of the workTo determine the nailfold capillaroscopic changes in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients and their relation to disease activity.Patients and methodsTwenty PsA and 20 RA patients were studied. Disease activity score (DAS28) was assessed. NFC examination was done to all patients.ResultsThere was a significant decrease in capillary density (8.65 ± 1.39 vs 9.5 ± 1/mm; p = 0.02) and increase in mean capillary width (28.4 ± 7.8 μm vs 22.9 ± 4.3 μm; p = 0.01) in PsA than RA patients. Hairpin, organized capillaries were found in all RA patients while in PsA patients tortuous capillaries were found in 100% and disorganized capillaries in 35%. A significant increase in hemorrhages (65% versus 10%; p < 0.0001) was present in PsA compared to RA patients. In PsA patients, there was a significant correlation between the tender joints count (TJC) and the width of the capillaries (r = 0.44, p = 0.047) and inversely with the capillary density (r = ?0.46, p = 0.04). The TJC significantly associated with the capillary disorganization (p = 0.035). A significant negative correlation between CRP titer and arterial diameter of capillaries (r = ?0.45, p = 0.045).ConclusionThe nailfold capillaroscopy in RA patients had no specific changes, While in PsA patients showed low density, dilated, tortuous and disorganized capillaries and hemorrhages. So, Nailfold capillaroscopy can be used in the differentiation between both diseases. NFC abnormalities may be related to the disease activity.     

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis

ObjectiveWe aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA).MethodsEleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted ‘yes’ (yes/no).ResultsThe systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients’ risk management.ConclusionsThis document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.     

Patient education and disease activity: A study among rheumatoid arthritis patients

Objective . To determine whether patients experiencing high disease activity derive more benefit from patient education than those experiencing low disease activity. Methods . Data from a randomized study on the effects of a program of patient education were analyzed retrospectively. Four subgroups were studied: the high disease activity subgroup of patients who had participated in the educational program, the complementary low disease activity subgroup, the high disease activity subgroup of controls, and its low disease activity complement. Patients with erythrocyte sedimentation rate >28 mm/first hour were classified as having high disease activity. Effects on frequency of physical exercises, endurance exercises, and relaxation exercises and effects on health status (Modified Health Assessment Questionnaire, Dutch Arthritis Impact Measurement Scales [AIMS]) were measured. Results . There were no significant differences between the adherence parameters of the various pairs of groups. Four months after the educational program began, anxiety and depression scores on the Dutch-AIMS had increased among participating patients who were experiencing high disease activity and decreased among those who were experiencing low disease activity. Conclusions . Patients experiencing high disease activity did not derive more benefit from patient education than those experiencing low disease activity. On the contrary, an increase of anxiety and depression is found in these patients. Further study is needed to confirm our findings.