Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. RESULTS: The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline. CONCLUSION: Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.     

Serological bone markers and joint damage in early polyarthritis

OBJECTIVE: To investigate the relationship between osteocalcin (OC), a marker of bone formation, and the recently developed serum marker of bone resorption, beta-C-telopeptide (beta-CTx), and radiographic damage in patients with early oligo- and polyarthritis. METHODS: Patients with peripheral arthritis of > or = 2 joints and < 2 years of symptom duration were studied. The OC and beta-CTx concentrations at baseline were correlated with disease activity and radiographic damage at baseline, and with radiographic progressive disease after 2 years (delta Sharp/van der Heijde score > or = 5). The additional value of serum bone metabolism markers to predict radiographic progressive disease was compared to that of established prognostic factors by multivariate logistic regression analysis. RESULTS: Two hundred seventy-nine patients (67% female; median age 56 yrs, range 18-83) were included in the study, of whom 73% were diagnosed with rheumatoid arthritis (RA). Baseline levels of beta-CTx (p < 0.05) were significantly correlated with baseline radiographic damage whereas OC was not. beta-CTx was also significantly (p < 0.001) related to measures of disease activity like erythrocyte sedimentation rate, C-reactive protein, and the disease activity score DAS28. Radiographic progressive disease after 2 years corresponded univariately with increased levels of beta-CTx (p < 0.001), but not with OC. In multivariate analysis, beta-CTx was not superior to other measures of radiographic progressive disease such as autoantibodies and disease activity. CONCLUSION: Increased serum levels of the bone turnover marker beta-CTx are associated with radiographic damage at baseline and radiographic progression after 2 years. However, beta-CTX is less predictive than markers already in use.     

DAS 28 for defining remission in rheumatoid arthritis in Indian patients

ObjectiveTo establish DAS 28 and DAS 28-3 scores that best define remission in Indian patients with rheumatoid arthritis (RA).Patients and MethodsAll patients diagnosed with RA visiting AIIMS, New Delhi over a period of 3 months were recruited. Clinical assessment included 28 joint counts for swelling and tenderness, duration of early morning stiffness, patient global assessment of disease activity, fatigue, joint pains and ESR. DAS 28 and DAS 28-3 scores were calculated and receiver operating characteristics curve analysis was performed to define cutoff values utilizing ‘ACR 5/6’ and ‘ACR 4/5’ remission criteria.ResultsSubjects included 207 patients (M: 44; F: 163) with mean age of 47.4 ± 12.6 years, median disease duration of 8 [4.12–14] years.‘ACR 5/6’ and ‘ACR 4/5’ criteria for remission were satisfied by 34 (16.42%) and 44 patients (21.25%) patients, respectively. DAS 28 score of 2.94 (sensitivity 84.4%, specificity 85.3%) and DAS 28-3 score of 3.02 (sensitivity 82.1%, specificity 82.4) best defined the ‘ACR 5/6’ remission. Corresponding values using ‘ACR 4/5’ remission were 3.04 (sensitivity 85.9%, specificity 84.1%) for DAS 28 and 3.05 (sensitivity 82.2%, specificity 81.8%) for DAS 28-3.ConclusionsA cutoff value < 3 for both DAS 28 and DAS 28-3 defines remission in RA in Indian patients.     

Predictors of radiographic joint damage in patients with early rheumatoid arthritis

OBJECTIVE: To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA). METHODS: New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used. RESULTS: 130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry. CONCLUSIONS: In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.     

The Nottingham Health Profile as a measure of disease activity and outcome in rheumatoid arthritis

Clinical measurement in rheumatoid arthritis (RA) has focused on articular problems. Although measures like the Health Assessment Questionnaire (HAQ) are widely used to determine functional impairment, there is a need to determine the overall effect of RA on general health status. We evaluated the relationship of a generic health status measure-the Nottingham Health Profile (NHP)-to the clinical, laboratory and radiological changes in the EULAR core data set for RA. Two hundred consecutive out-patients with RA were recruited. Their mean age was 58.9 yr and mean disease duration 11.3 yr. Patients completed the NHP and the following assessments were made: the EULAR Core Data Set, the duration of morning stiffness, the Disease Activity Score (DAS), rheumatoid factor (RF) levels, and Larsen's score for X-rays of hands and wrists. RA patients had higher scores on the NHP than both a random population sample and a second sample of patients with a variety of common diseases. NHP scores were not related to age or disease duration in RA. There was little relationship between perceived distress and the Larsen score, RF, ESR and C-reactive protein levels. Moderate associations were seen between NHP scores and disease activity measures, including the number of tender and swollen joints, pain and the duration of early morning stiffness, and also with a disability measure-the HAQ. NHP scores were highly related to disease activity measured by DAS. High DAS scores were associated with high scores in the energy level, pain and sleep sections of the NHP. The NHP gives relevant information about RA patients. They have high scores for pain, physical mobility and energy level sections, and also have high distress for sleep and emotional reactions.      

Functional disability in relation to radiological damage and disease activity in patients with rheumatoid arthritis in remission

OBJECTIVE: To investigate the relationship between functional disability, disease activity and radiological damage in patients with rheumatoid arthritis (RA) in remission. METHODS: One hundred and eighty-six patients with RA in remission or with low disease activity were studied. The following variables were assessed at one time point: joint count, visual analog scale for pain, functional disability, i.e., health assessment questionnaire (HAQ) score, radiological joint damage as assessed by radiographs of hands and feet and scored according the Sharp-van der Heijde method, and presence of comorbidity. Disease activity was expressed as the disease activity score (DAS). Correlations were calculated by Spearman's rho coefficient of correlation. In addition, variables associated with the score were analyzed by logistic regression. RESULTS: The median HAQ score was 0.25 [interquartile (IQR) range 0-0.75] and the median DAS was 1.0 (IQR 0.7-1.5). Of the 186 RA patients included, 82% were in remission according to the DAS. The median joint damage as assessed by the Sharp-van der Heijde score was 21 (IQR 9-74). Functional disability was significantly correlated with pain (rho 0.48, p < 0.001), disease activity (rho 0.42; p < 0.001), disease duration (rho 0.39; p < 0.001), radiographic joint damage (rho 0.37; p < 0.001), and age (rho 0.19; p = 0.01). In a logistic regression model functional disability was independently related to presence of pain, disease activity, radiographic joint damage and disease duration in decreasing order of strength, but not to age. sex and co-morbidity. CONCLUSION: Patients with RA who are in remission might experience minimal functional disability and radiographic joint damage. Functional disability in RA patients in remission is most strongly related to the presence of pain and in lesser extent to disease activity, radiographic joint damage, and disease duration.     

Diagnostic value of anti-cyclic citrullinated peptide antibodies in northern Chinese Han patients with rheumatoid arthritis and its correlation with disease activity

This study was to evaluate the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in northern Chinese Han patients with rheumatoid arthritis (RA) and its correlation with disease activity. Clinical data and serum samples were collected from 112 RA patients and 55 non-RA patients. Statistical analyses of the correlations among anti-CCP antibodies, other serological markers, and the RA patients’ clinical characteristics were performed using SPSS 11.5 software. Anti-CCP antibodies were detected in 77.7% of all RA patients and 80.4% of the RA patients with a disease duration of 3 years or less. The combined diagnosis using high titer anti-CCP antibodies (≥100 RU/ml) with a concomitant positive rheumatoid factor (RF) test exhibited the greatest diagnostic specificity; it achieved 87.9% for all RA patients and 90.1% for the patients with disease duration of three years or less. Moreover, anti-CCP antibodies showed medium correlations to the RA patient’s serum RF titer (r?=?0.560, P?<?0.001) and disease activity (DAS28 score; r?=?0.404, P?<?0.001). Compared with the patients with low anti-CCP antibody titers (<100 RU/ml), patients with high anti-CCP antibody titers showed higher RF titers, worse DAS28 scores, and severe morning stiffness (P?<?0.01). This study suggests that anti-CCP antibodies can be used for RA diagnosis and disease activity evaluation for northern Han Chinese patients. A combined diagnosis using both high titers of anti-CCP antibodies (≥100 RU/ml) and a positive RF test markedly improves RA diagnostic specificity. Patients’ DAS28 scores rise and morning stiffness intensifies with increasing anti-CCP antibody titers.     

Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study

OBJECTIVE: To evaluate whether early combined therapy with methotrexate (MTX) and sulfasalazine (SSZ) during the first year in early rheumatoid arthritis (RA) induces long term beneficial effects, compared with monotherapy, when the further treatment strategy is a free choice. METHODS: Study design: five year multicentre prospective longitudinal trial. Participants: 146/205 patients with RA previously included in a one year prospective randomised trial comparing the effects of treatment with MTX, SSZ, or a combination of both. Criteria for inclusion: patients with early RA (< or =1 year duration). Follow up: between the end of years 1 and 5, patients were followed up and treated by their own rheumatologist, who was allowed to indicate any treatment. Outcome measures: disease activity score (DAS), health assessment questionnaire (HAQ), and Sharp/van der Heijde radiological score at baseline and after five years of follow up. Analysis: comparison of the five year follow up DAS, HAQ, and radiological scores in patients given combined and single treatment during the first year. RESULTS: At the end of the five years of follow up, the patients primarily receiving single or combined treatment had similar mean DAS, HAQ, and radiographic scores. CONCLUSION: Treatment of patients with early RA using combined therapy with MTX and SSZ during the first year did not influence the long term inflammatory status, or disability, or structural changes, compared with single disease modifying antirheumatic drug treatment.     

Measurement of disease activity in psoriatic arthritis. Extended report

OBJECTIVE: To determine whether activity indices, generally accepted in rheumatoid arthritis (RA) are useful and valid to measure disease activity in psoriatic arthritis (PsA) patients with peripheral arthritis. METHODS: 38 PsA patients were studied before and after a one year DMARD treatment. Extended and reduced tender and swollen joint counts, Ritchie articular index, Health Assessment Questionnaire HAQ) score, erythrocyte sedimentation rate (ESR) morning stiffness, the patient's and the assessor's global assessment (PGA and AGA) were recorded. Disease activity scores, EULAR, ACR and Clegg improvement criteria were calculated. RESULTS: All indices correlated well before and after treatment with AGA (r > 0.337, p < 0.042), except morning stiffness and tender joint counts. After treatment, PGA correlated well only with the 68 and 28 tender joint counts, ESR and HAQ (r > 0.340, p < 0.05). The response to DMARD treatment was well characterized with the changes in the number of tender and swollen joint counts, and DAS4, DAS3, DAS28. The changes correlated with the PGA and AGA. The level of agreement between Clegg and the EULAR improvement criteria with both extended and reduced joint count was comparable (p < 0.01). CONCLUSION: The well-known activity indices generally accepted in RA, as tender and swollen joint count, DAS3, DAS4, DAS28, are useful and valid indices measuring arthritis activity in PsA with peripheral arthritis. The correlation between Clegg and EULAR improvement classification indices were similar. Both seemed to characterize changes authenticated during DMARD treatment.     

Predictive factors of 5-year health assessment questionnaire disability in early rheumatoid arthritis

OBJECTIVE: To determine prognostic factors of disability in early rheumatoid arthritis (RA) and to investigate the radiological and functional course of the disease. METHODS: A total of 191 patients with early RA (diagnosed for less than one year) according to American College of Rheumatology criteria were followed prospectively for 5 years. At baseline and at endpoint, Stanford Health Assessment Questionnaire (HAQ) scores and radiological scores (Sharp's score modified by van der Heijde) were performed. Correlations between numerous baseline data and HAQ score at endpoint were analyzed, using nonparametric tests. A multilinear regression model was performed to select independent prognostic factors of HAQ disability. RESULTS: During the 5-year followup, mean HAQ decreased from 1.3 (+/- 0.7) to 0.6 (+/- 0.6). There were 98 (65.3%) patients with a score > 1 point at baseline, but only 46 (27.4%) after 3 years and 34 (21.8%) after 5 years. Moreover, 90% of the patients had an improvement of the disability score. Final HAQ disability was associated with baseline values of HAQ score, Pain, Ritchie index, tender joint count, Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and erosion. Multivariate analysis selected baseline HAQ score, Ritchie index, ESR, CRP, and presence of erosion as independent prognostic factors of HAQ disability. The probability cutoff in the logistic model was selected to minimize the sum of false positive and false negative values: negative predictive value = 92.71%, positive predictive value = 46.15%, p = 0.408. Sex, age, IgM and IgA rheumatoid factors, other tested autoantibodies, and HLA class II genes did not contribute significantly to prediction of the disability after 5 years. At baseline, mean scores were 3.6 units (+/- 7.7) for total radiological score, 1.7 (+/- 4.5) for erosion score, and 1.9 (+/- 3.7) for joint space narrowing score. After 5 years, they were 17.9 +/- 22.3, 6.9 +/- 9.5, and 11.0 +/- 15.4, respectively. No erosion was present at the start in 58.0% of patients, compared to 24.2% and 22.4% at 3 and 5 years. Global radiographic progression concerned 87 patients (55.8%) during the 5 years. CONCLUSION: During the first 5 years of RA, radiological damage increased progressively in half of the patients, whereas HAQ disability improved in most of them during the same period of time and could be predicted by baseline values of HAQ score, Ritchie index, ESR, CRP, and presence (or absence) of erosion.     

Radiological damage in patients with rheumatoid arthritis on sustained remission

OBJECTIVE: To assess the radiological damage progression in patients with recent rheumatoid arthritis in sustained remission. METHODS: A cohort of 191 patients with active early (<1 year) rheumatoid arthritis was prospectively assessed at baseline, 3 and 5 years by the Disease Activity Score (DAS) and the Sharp-van der Heijde Score (SHS) for radiographic damage. Patients in remission (DAS<1.6) at the 3-year and 5-year time points were compared with patients with a persistently active rheumatoid arthritis by Wilcoxon's signed rank test. RESULTS: 57 patients died, were lost to follow-up or had incomplete data; 30 (15.7% of those who completed) patients were in remission at 3 and 5 years. The SHS in these two groups was not significantly different at baseline (p = 0.15), but was lower in the remission group at 5 years (p = 0.0047). The median (IQR) radiographic score increased from 0.5 (0-7) at baseline to 2.5 (0-14) after 5 years for the remission group (p = 0.18) and from 2 (0-7) to 13 (3-29) in the group with active rheumatoid arthritis (p<0.001). 5 (16.7%) patients in remission had relevant progression of radiographic damage (ie, progression >4.1 points) and 6 (20%) presented new erosions in a previously unaffected joint between the third and the fifth years. CONCLUSION: Patients with early rheumatoid arthritis in sustained remission did not present statistically significant radiographic degradation at the group level; nevertheless, 16.7% of these patients did present degradation. Absence of progression should be part of the remission definition in rheumatoid arthritis.     

Serum cytidine deaminase levels after withdrawal of non-steroidal anti-inflammatory treatment in rheumatoid arthritis.

Increases in joint inflammation in nine patients with rheumatoid arthritis were provoked by withdrawal of their non-steroidal anti-inflammatory drugs. Pain score, duration of morning stiffness, Ritchie articular index score, and the number of analgesic tablets consumed reached peaks after five, three, five, and five days respectively compared with values during six days of normal treatment. Changes in serum cytidine deaminase (believed to reflect polymorph turnover in inflamed joints) showed a different pattern, with a sharp peak after two days and a subsequent trough. Possible mechanisms for these differences are discussed.     

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.     

A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up

OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.     

The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years

OBJECTIVE: This prospective study analyzed influence of patient's sex on early rheumatoid arthritis (RA) within one year of disease onset and after 2 years' followup. METHODS: A total of 844 consecutive patients, 538 women, with RA of less than 12 months were studied. Standardized clinical and radiographic assessments were performed at study entry and after 2 years. The association of several variables at study entry with the outcome variables Disease Activity Score (DAS28), functional disability measured by the Health Assessment Questionnaire (HAQ), and, in 390 patients, Larsen score at the 2-year followup were analyzed in men and women separately. RESULTS: At study entry the women were younger compared with the men and the sexes showed different age distributions. The women had higher DAS28 and HAQ scores. However, women below 50 years of age at study entry had milder disease than older women and close to that of men. At 2-year followup the women still had higher DAS28 and HAQ scores compared to men, who had achieved remission in a higher frequency. Larsen score showed no sex difference either at study entry or after 2 years. Presence of rheumatoid factor (RF) was associated with lower age at study entry and higher DAS28 at followup in men only. Higher DAS28 and HAQ scores at entry were more strongly correlated with severe disease at followup in women than in men. Presence of the "shared epitope" was not associated with age or the outcome variables DAS28 and Larsen score in either sex. CONCLUSION: The disease phenotype in early RA was significantly different between men and women, particularly concerning age, disease activity, and functional capacity. There were differences between the sexes concerning early disease characteristics associated with outcome at 2 years of followup.     

Ultrasonography predicts achievement of Boolean remission after DAS28-based clinical remission of rheumatoid arthritis

Abstract

Objectives. To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria.

Methods. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint.

Results. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score.

Conclusions. Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of “deeper remission” of RA.     

What factors influence functional ability in patients with rheumatoid arthritis. Do they alter over time?

OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.     

An eight year prospective study of outcome prediction by antiperinuclear factor and antikeratin antibodies at onset of rheumatoid arthritis

OBJECTIVES: Antikeratin antibodies (AKA) and antiperinuclear factor (APF) are specific antibodies found very early in rheumatoid arthritis (RA). The objective of this eight year follow up study was to assess the value of early AKA and APF assays in predicting functional disability and cartilage damage. METHOD: In 2000, 64 patients tested for AKA and APF (antifilaggrin antibodies) between 1990 and 1993 during evaluation of early symmetric oligoarthritis or polyarthritis (suspected RA) were invited to participate in this non-concurrent cohort study. The Health Assessment Questionnaire (HAQ) score, disease activity score (DAS), and Larsen radiographic score were the primary evaluation criteria. RESULTS: Twenty nine patients were re-evaluated. Clinical and laboratory data obtained in 1993 were similar in this group and in the 35 other patients. Twenty five patients had received a diagnosis of RA. Nine (31%) were rheumatoid factor (RF) positive, nine (31%) were AKA positive, and six (21%) were APF positive during the first year of the disease. APF was correlated with the Larsen score (p=0.011) and DAS (p=0.035) evaluated after a mean disease duration of 8.55 years. All APF positive patients had erosive disease. AKA was correlated with the DAS (p=0.035). CONCLUSION: The presence of AKA or APF early in the course of RA was associated with the DAS or Larsen score eight years later. The number of patients was small, but the findings confirmed those of studies with shorter follow ups. Antifilaggrin antibodies should be included in the initial investigation of patients with RA and, when positive, should alert to a high risk of poor outcomes.     

Prognostic factors for joint destruction in rheumatoid arthritis: a prospective longitudinal study of 318 patients

OBJECTIVE: To quantify articular damage and to investigate prognostic factors for joint damage progression in rheumatoid arthritis (RA). METHODS: RA patients satisfying the 1987 American College of Rheumatology criteria and with disease duration under 5 years were sampled from the EURIDISS longitudinal cohort study in Norway, The Netherlands, and France. Hand radiographs were assessed at baseline and at 2 to 3 year followup using Sharp score modified by van der Heijde. Assessment of erosion and joint space narrowing, performed in sequential order by a single reader blinded to patients' characteristics, had high intraobserver reproducibility (intraclass correlation coefficient 0.98-0.99). Baseline prognostic factors were analyzed in a multivariate linear regression model. RESULTS: A total of 318 patients with RA aged 52.4 years (70.4% were female) and with a mean 2 years' disease duration at baseline were followed over 30 months. Median (quartiles) baseline and followup modified Sharp scores were 3 (0-11) and 9 (1-27), respectively, with 35.8% and then 22.3% of patients with no radiological damage. Controlling for age, sex, and country, the final joint damage was predicted by baseline modified Sharp score, rheumatoid factor positivity, time from disease diagnosis, patient global health assessment, and erythrocyte sedimentation rate, and by followup duration, explaining 76.8% of the outcome variance. CONCLUSION: This multinational study confirmed the prognostic role in RA of a set of features previously identified in smaller cohorts. It indicates which disease characteristics should be focused on in the early years of RA to identify patients at higher risk of developing severe disease and who are candidates for aggressive therapy.     

Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis

OBJECTIVE: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. METHODS: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. RESULTS: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant. CONCLUSION: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.