Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis

OBJECTIVE: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). METHODS: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months. CONCLUSION: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.     

The 2010 ACR/EULAR classification criteria for rheumatoid arthritis in the Heinola inception cohort—diagnoses confirmed by long-term follow-up

The aim of this study was to evaluate the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) in a cohort with early arthritis and true diagnosis confirmed by long-term follow-up. The criteria were tested in the Heinola community-based inception cohort of 121 true RA patients, while the control group consisted of 95 patients with definite spondyloarthritis and swollen joint(s), recruited in the same time. The diagnoses were confirmed by long-term follow-up. The fulfillment of the four 2010 criteria was determined at baseline (arthritis duration less than 6 months). Ninety-five in one hundred twenty-one (79%) of all RA patients, 54/68 (79%) of nonerosive (at baseline) RA patients, and 4/95 (4%) of controls fulfilled the 2010 criteria of RA, with better specificity (96%) than the 1987 ACR criteria (86%) in the same material. At baseline erosions were found in 44% of all RA patients and in 15% of the controls; rheumatoid factor was positive in 87% of the RA patients, but in 1% of the controls. One hundred seven in one hundred twenty-one (88%) of all RA patients and 16/95 (17%) of the controls fulfilled the 2010 total score criteria or were erosive at onset. The 2010 ACR/EULAR criteria should be documented in all patients with arthritis. If the criteria are not fulfilled at baseline in a nonerosive patient, the true diagnose may still be RA due to seroconversion or diagnostic manifestations during the follow-up. Indications for early disease modifying antirheumatic drug treatment may be present in active arthritis also in cases not fulfilling the new criteria at baseline.     

Remission in rheumatoid arthritis: wishful thinking or clinical reality?

OBJECTIVES: To review the concept of remission in rheumatoid arthritis (RA), as defined by the Food and Drug Administration (FDA), the American College of Rheumatology (ACR), and the European League Against Rheumatism (EULAR). To delineate differences between significant clinical improvements, very low disease activity, and the achievement of true remission. To evaluate the prevalence of these outcomes with biologic therapy and traditional disease-modifying antirheumatic drugs (DMARD) regimens. METHODS: The MEDLINE database was searched for the key words "remission" and "rheumatoid arthritis." Efficacy data of RA clinical trials from 1985 to 2004 are based on a literature review of medical journals and abstracts from rheumatology meetings. We review 3 well-defined sets of criteria established by the ACR, EULAR, and the FDA for measuring remission. RESULTS: Defining remissions in clinical trials and clinical practice requires appropriate standardized and objective outcome measures, such as the ACR and EULAR remission criteria. Traditional DMARDs often provide symptom relief, improvements in physical function, and the slowing of radiographic progression in patients with RA, but rarely lead to the complete cessation of RA activity. Remission, as defined by the ACR criteria, has been observed in 7 to 22% of patients treated with traditional DMARD monotherapy (ie, gold, penicillamine, methotrexate [MTX], cyclosporine A, or sulfasalazine), but these remissions have often been short-lived. Treatments with DMARD combinations, biologic monotherapy, and biologic combination therapy with MTX offer greater hope and may facilitate the higher rates of remission. Clinical trial results have shown that newer DMARDs such as leflunomide or the combination of multiple DMARDs can generally elicit greater EULAR remission rates (ranging from 13 to 42%) than monotherapies. Biologic combinations with MTX have also been shown to induce significant remission (as defined by the EULAR criteria) in RA patients, with a 31% rate observed with infliximab plus MTX at 54 weeks, a 50% rate observed for adalimumab plus MTX after 2 years of therapy, and a 41% rate observed for etanercept plus MTX after 2 years of therapy. CONCLUSIONS: In the era of biologics and combination therapy, identifying remission or at least very low disease activity as the ultimate goal in RA therapy should become the new standard for the outcome of all RA trials. The criteria established by the FDA, the ACR, and the EULAR represent an important step toward achieving this goal.     

Lipid profiles among US elderly with untreated rheumatoid arthritis--the Third National Health and Nutrition Examination Survey

OBJECTIVE: Recent studies suggest that patients with active rheumatoid arthritis (RA) have adverse serum lipid profiles. We examined lipid profiles among individuals with RA in a national sample of persons aged 60 years and older. METHODS: Using data from 4862 participants (2379 men and 2483 women) aged 60 years and older in the Third National Health and Nutrition Examination Survey (1988-94), we examined lipid profiles among participants with RA who met the American College of Rheumatology (ACR) 1987 criteria and who were not taking glucocorticoids or disease modifying antirheumatic drugs (DMARD). RESULTS: Participants with RA had lower high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I concentrations than those without RA. After adjusting for age and sex, the differences in HDL-C level between those with and those without RA were 2.5 mg/dl (95% CI 0.8 to 4.9) using > or = 3 of the ACR criteria (n of RA cases = 104) and 8.8 mg/dl (95% CI 3.2 to 14.3) using > or = 4 criteria (n of RA cases = 26). Adjusting for age, sex, race, education, smoking status, body mass index, alcohol consumption, physical activity, dietary factors, and other potential confounders attenuated the differences slightly. The multivariate difference in serum apolipoprotein A-I levels between those with and those without RA was 4.5 mg/dl (95% CI -0.8 to 9.8) using > or = 3 ACR criteria and 13.6 mg/dl (95% CI 3.2 to 24.1) using > or = 4 criteria. All individual RA disease activity measures tended to have inverse relations with HDL-C levels, but significant inverse associations were present only with the following variables: C-reactive protein [CRP; multivariate difference per 1 mg/dl of CRP, -1.3 mg/dl (95% CI -2.0 to -0.5)], presence of hand arthritis [-2.6 mg/dl (95% CI -5.0 to -0.2)], and positive rheumatoid factor [-3.4 mg/dl (95% CI -5.5 to -1.3)]. CONCLUSION: These national survey data indicate that RA not treated with DMARD or glucocorticoids is associated with adverse lipid profiles characterized by lower HDL-C and apolipoprotein A-I levels in persons aged > or = 60 years.     

Does the age of onset of rheumatoid arthritis influence phenotype?: a prospective study of outcome and prognostic factors.

OBJECTIVE: To identify factors affecting prognosis in patients with late-onset rheumatoid arthritis (RA). METHODS: A total of 400 patients with RA fulfilling the American College of Rheumatology criteria for diagnosis were prospectively recruited from two hospital rheumatology centres. Of these patients, 214 had disease onset above age 65 yr (LORA) and 186 below age 65 yr (YORA). Follow-up clinical, functional, laboratory and radiological assessments were compared. The Ritchie articular index (RAI) and joint erosions were used as markers of disease activity and damage, respectively. Disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). RESULTS: At median follow-up of 3.6 yr, the frequency of joint erosions was similar (YORA, 51.6%; LORA, 54.2%). The remission rate was greater in the LORA group (YORA, 20.4%; LORA, 45.8%, P < 0.01). Factors associated with the development of erosions were: IgM rheumatoid factor (RF) seropositivity [odds ratio (OR) = 4.24, 95% confidence interval (CI) 2.56, 6.94], HLA DR4 (OR = 2.07, 95% CI 1.28, 3.35) and elevated inflammatory markers (OR = 1.81, 95% CI 1.04, 3.14). Continuous steroid use >3 months for the LORA group was associated with increased erosions (OR = 4.09, 95% CI 1.81, 9.27). LORA patients (OR = 2.99, 95% CI 1.77, 5.02) were more likely to go into remission and IgM RF-seropositive patients less likely to go into clinical remission (OR = 0.47, 95% CI 0.28, 0.77). Female patients with a high HAQ score at presentation experienced a poor functional outcome (female OR = 3.01, 95% CI 1.59, 5.68; high HAQ OR = 3.02, 95% CI 1.98, 4.62). CONCLUSION: LORA can be as damaging as classical RA and joint erosions are often observed at presentation. Being RF seropositive, DR4 positive, and having elevated inflammatory markers at onset, were associated with poor radiological outcome irrespective of age of onset. Being female and having marked disability at presentation were associated with poor functional outcome in both groups. These findings suggest that treatment approaches used in classical YORA should be instituted with equal vigour in patients with LORA.     

Clinical, laboratory and genetic markers associated with erosions and remission in patients with early inflammatory arthritis: a prospective cohort study

We investigated the relationship between clinical, laboratory and genetic markers and outcome measures in 159 patients with recent onset of inflammatory arthritis (IA). The majority of patients were managed in community-based rheumatology practice. Median duration of arthritis at baseline was 3 months with median follow-up of 4.0 years (range 0–10). Markers of disease activity and 1987 ACR criteria for rheumatoid arthritis (RA) were estimated every 6 months for the first 2 years and annually thereafter. Presence of shared epitopes (SE) was established by PCR-based method. Main outcome variables were attainment of remission and presence of erosions on X-rays of hands and feet at 3 years. Remission was seen in 34.3% of patients and was independently related to age 60 and older (odds ratio (OR) 3.2; 95% confidence interval (CI), 1.2–8.7) and inversely to the presence of rheumatoid factor (RF) (OR 8.3; 95% CI, 3.2–21.3 for persistent arthritis). Patients with two SE were likely to have persistent arthritis (P=0.006), but this was not significant when corrected for RF. Independent predictors for erosions at 3 years were RF (OR 7.5; 95% CI, 1.9–29.5) and area under the curve for number of swollen joints (OR 1.08; 95% CI, 1.02–1.16). SE status was not predictive of erosions at 3 years (OR 1.6; 95% CI, 0.7–3.7). In univariate analysis, patients possessing DERAA motif on DRB1 were less likely to have erosive disease than without this motif at 4 years (OR 0.21; 95% CI, 0.0–0.9, P=0.037) but this finding was partly explained by adjusting for RF (adjusted OR 0.24; 95% CI 0.04–1.37). In this study of recent onset IA, active disease and RF were associated with poor outcome. Whilst SE did not predict erosive disease, patients with DERAA motif may be protected against erosions whilst the presence of two SE alleles suggests persistence of arthritis.     

Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis?

Objectives: To study which cut off point of DAS28 corresponds to fulfilment of the American Rheumatism Association (ARA) preliminary remission criteria, and clinical remission criteria in patients with rheumatoid arthritis (RA). Methods: All adult patients diagnosed with RA at Jyväskylä Central Hospital 1997–98 were assessed for remission at 5 years. Remission was defined as (a) ARA remission; (b) clinical remission (defined as no tender or swollen joints and normal erythrocyte sedimentation rate). DAS28 was used to measure disease activity. A receiver operating characteristics curve analysis was performed to calculate a cut off point of DAS28 that best corresponds to the ARA remission criteria and the clinical remission criteria. Results: 161 patients (mean age 57 years, 107 (66%) female, 98 (61%) with positive rheumatoid factor, and 51 (32%) with erosions) were studied. At 5 years, 19 (12%) patients met the ARA remission criteria, and 55 (34%) met the clinical remission criteria. The cut off value of DAS28 was 2.32 for the ARA remission criteria, and 2.68 for the clinical remission criteria. In patients with DAS28 <2.32, 11/57 (19%) had tender joints, 6/57 (11%) had swollen joints, and 4/57 (7%) had both tender and swollen joints (66 joint count). Conclusion: In this study the DAS28 cut off point for the ARA remission was lower than in previous studies. The cut off point for DAS28 remission remains controversial. A substantial proportion of patients below the DAS28 cut off point for remission have tender or swollen joints, or both. DAS28 may not be an appropriate tool for assessment of remission in RA.     

Prevalence of rheumatoid arthritis and hepatitis C in those age 60 and older in a US population based study

OBJECTIVE: A positive association between rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection has been reported in clinic based cross sectional studies. We investigated if RA and HCV are associated in a population based survey. METHODS: Using data from the National Health and Nutrition Examination Survey III, hepatitis C and RA status were determined for subjects > or = 60 years of age. RA was defined to be present when 3 of 6 American College of Rheumatology (ACR) criteria were met. RESULTS: Of 6596 subjects, 1827 (27.7%) were excluded due to missing data. Of the remaining 4769, 196 subjects (4.1%) met our modified ACR criteria for probable RA: 63 tested positive for anti-HCV antibodies (1.3%) while 35 were HCV RNA positive (0.7%). Two subjects had both HCV antibodies and RA, while one subject was both HCV RNA positive and had RA. HCV antibody positivity was not associated with RA (OR 0.44, 95% CI 0.07-2.80). Similarly, HCV positivity by polymerase chain reaction was not associated with RA (OR 0.77, 95% CI 0.10-6.19). CONCLUSION: These results argue against a potential role for HCV in the etiology of RA in the US population aged 60 years and over.     

Late-onset rheumatoid arthritis: is pitting oedema of the hands at onset a good prognostic indicator?

This prospective study compares the clinical and radiological outcome of patients with late-onset (age 65 yr and over) rheumatoid arthritis (RA) presenting with and without pitting oedema of the hands (POH). Twenty-two patients with POH (Group 1) were compared with 81 (Group 2) without POH (median age of onset of RA-Group 1: 74.3; Group 2: 73.1; female to male. ratio-Group 1: 1.2:1; Group 2: 2.5:1). The median time between the onset of arthritis and baseline assessment was 3 months. Minimum follow-up was 1 yr (median 2.4). Outcome was defined by (1) the development of erosions of the hands, wrists or feet and (2) the number of patients in remission (clinically inactive disease on two clinic visits 3 months apart with no intervening history of inflammatory joint disease). IgM rheumatoid factor (IgM RF) was less frequent in patients with POH (Group 1:8.2%; Group 2: 43.2%, P < or = 0.05). Logistic regression analysis showed that POH at onset was independent of IgM RF in determining outcome. Patients with POH were less likely to develop erosions [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.03, 0.89]. Although initial cross-tabulation suggested an increased frequency of remission in Group 1 (Group 1: 90.9%; Group 2: 55.5%, P = 0.02), POH was not found to be a significant predictor using the logistic regression model (OR = 7.42, 95% CI 0.84, 65.7). Patients with IgM RF were more likely to develop erosions (OR = 5.1, 95% CI 1.46, 17.67) and less likely to go into remission (OR = 0.19, 95% CI 0.06, 0.68).      

Prognostic markers of clinical remission in early rheumatoid arthritis after two years of DMARDs in a clinical setting

OBJECTIVE: To analyze the rate and baseline prognostic factors of clinical remission in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy based on a structured algorithm using disease-modifying anti-rheumatic drugs (DMARDs) in a clinical setting. To determine whether a good therapeutic response at 6 months of therapy is associated with remission at 2 years. METHODS: One hundred and five patients (81% female) with early RA (disease duration < 2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was clinical remission after 2 years of DMARD therapy using the 28-joint disease activity score (DAS28 < 2.6). Clinical, biological, immunogenetic and radiographic data (Larsen score) were analyzed at study entry and after 6, 12, 18 and 24 months of follow-up. Therapeutic response was analyzed using the ACR and EULAR criteria. RESULTS: Remission was observed in 34 patients (32.4%) after 2 years of follow-up. A baseline DAS28 score < 5.1 (p = 0.004), hemoglobin (p = 0.04) and male gender (p = 0.02) were associated with remission in the univariate analysis. In the multivariate logistic regression analysis, only a DAS28 < 5.1 was associated with remission at 2 years (OR 4.1, 95% CI: 1.56;10.77, p = 0.004). The percentage of ACR50 responses after 6 months was significantly higher in patients with remission at 2 years than in those without (66.7% vs 43.3%; p = 0.04). Similar results were obtained when analyzing the good EULAR response (50% vs 20.9%; p = 0.003). Furthermore, when the therapeutic response at 6 months was included in the logistic regression model, only an ACR50 response (OR 3.9, 95% CI 1.14;13.38, p = 0.03) and a good EULAR response (OR 6.23, 95% CI 1.61; 24.04, p = 0.008), but not an ACR20 response or a whole EULAR response were significantly associated with remission. CONCLUSION: In a series of early RA patients treated using a structured algorithm with DMARDs and very low doses of glucocorticoids, clinical remission was observed in one-third of patients after 2 years. Low or moderate disease activity (DAS28 < 5.1) at baseline and a good therapeutic response during the first months of therapy predicts clinical remission at 2 years.     

Cigarette smoking and rheumatoid arthritis severity

OBJECTIVES—Cigarette smoking may influence rheumatoid arthritis (RA) disease incidence and may have direct biological effects on the lungs and systemically. This study sought to determine if cigarette smoking is associated with RA disease severity.
METHODS—Clinical evaluations of patients seen in the University of Iowa rheumatology and orthopaedic ambulatory clinics were conducted. A letter of interest was mailed to 1701 patients who were first assigned an ICD-9-CM diagnostic code for RA in one of these clinics. A total of 857 patients expressed interest and were offered a clinical examination and 395 were evaluated over an 18 month period. Of these, 336 satisfied examiner criteria for prevalent RA and were included in the analysis. The disease characteristics and arthritis care utilisation of these patients seemed representative of prevalent cases in the general community. RA disease severity was assessed by radiographic bone erosions (graded as either present/absent and using the Larsen system), rheumatoid factor seropositivity, and presence of subcutaneous rheumatoid nodules.
RESULTS—Pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity (p = 0.0001), radiographic erosions (p = 0.024), and nodules (p = 0.051). After adjustment for potential confounders, smokers with ≥25 pack years were 3.1 times more likely to be rheumatoid factor positive (95% CI 1.7, 5.6) and 2.4 times more likely to show radiographic erosions (95% CI 1.2, 4.5) than never smokers. Less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease.
CONCLUSION—Cigarette smoking may adversely influence the severity of RA in a potentially dose dependent fashion.

     

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

Objective. To analyse the proportion of individuals in the generalpopulation over age 50 who do not meet American College of Rheumatology(ACR) criteria for rheumatoid arthritis (RA) remission, andOMERACT criteria for minimal disease activity (MDA), and tocompare results to RA patients. Methods. A self-report questionnaire was completed by 1400 communitycontrol subjects and 1705 RA patients, including the HealthAssessment Questionnaire (HAQ), gradual rating scales for pain,fatigue and global health, duration of morning stiffness andpainful joints. The prevalence of 4/6 ACR remission criteriaand 4/7 OMERACT criteria for MDA was analysed in community controlsubjects and patients with RA over age 50. Results. For ACR criteria, 76% of control subjects reportedpainful joints, 37% morning stiffness, 62% pain and 66% fatigue,vs 94, 65, 84 and 84% of patients with RA. MDA criteria werenot met by 64% of control subjects for painful joints, 38% forpain, 45% for global health and 18% for HAQ, vs 89, 60, 69 and52% of RA patients. The four ACR remission criteria were metby 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 50did not meet criteria for remission or MDA in RA. Although aself-report format may differ from results involving an assessor,the current criteria may not be accurate to identify remissionor MDA in people with RA who are older than age 50. KEY WORDS: Rheumatoid arthritis, Remission criteria, Minimal disease activity, Population Submitted 8 November 2006; revised version accepted 7 February 2007.     

Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class II alleles in systemic lupus erythematosus

OBJECTIVE: To determine the associations of erosive arthritis (EA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and major histocompatibility class (MHC) II alleles in systemic lupus erythematosus (SLE). METHODS: One hundred four patients with SLE were evaluated for arthritis and classified as EA, nonerosive arthritis, or no arthritis. EA was further classified as major or minor erosions. Sera from patients and 130 serum controls were tested for anti-CCP2 and rheumatoid factor (RF). Patients and 117 genetic controls were genotyped for HLA-DRB1 and HLA-DQB1. Statistical associations were tested using chi-square tests and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Eight patients (8%) were anti-CCP+ and they accounted for 11% (8/71) of patients with synovitis. Twelve patients (11%) had EA. Among patients with synovitis, EA was associated with anti-CCP (OR 28.5, 95% CI 4.7-173.8, p = 0.001), with a weaker association for RF (p = 0.3). Six patients with EA had major erosions and also met criteria for rheumatoid arthritis (RA). Four of these patients (67%) were anti-CCP+. HLA-DQB1*0302 was associated with EA (p = 0.01), with similar trends for HLA-DRB1*0401 and 2 copies of the shared epitope (SE). There were trends for associations of HLA-DQB1*0302 and 2 SE copies with anti-CCP production. CONCLUSION: The frequency of EA in SLE is likely to be higher than previously reported. Anti-CCP+ patients with SLE are more likely to have EA. Anti-CCP may be a useful serological marker for EA for patients presenting with synovitis. Anti-citrulline antibodies may have a pathogenic role in the development of major erosions, resulting in clinical features that overlap SLE with RA (rhupus).     

The radiographic criterion in the 1987 revised criteria for rheumatoid arthritis. Reassessment in a prospective study of early disease.

OBJECTIVE. To assess the radiographic criterion in the 1987 revised criteria for the classification of rheumatoid arthritis (RA), in patients with early RA. METHODS. The diagnostic value of radiologic changes in the hands was compared with that of radiologic changes in the feet, in a prospective study of 78 patients with early definite or classic RA (symptoms for less than or equal to 12 months) according to the 1958 criteria. RESULTS. At entry, 23% of the patients had erosions only in metatarsophalangeal (MTP) joints, 6% only in hands, and 5% both in hands and in feet. After 2 years of followup, 29% of the patients had only MTP joint erosions and 3% had only hand erosions. At study entry, the level of clinical activity in patients with erosions in the feet only was lower than that in other patients, and 44% of these patients would not have been diagnosed as having RA by the 1987 criteria. CONCLUSION. In early RA, radiographic changes in the feet seem to be a more sensitive criterion than radiographic changes in the hands. Therefore, addition of radiographic evaluation of the feet to the revised criteria may improve the classification of recent-onset RA.     

The importance of reporting disease activity states in rheumatoid arthritis clinical trials

OBJECTIVE: To compare the value of reporting treatment effects in rheumatoid arthritis (RA) as relative change from baseline (e.g., American College of Rheumatology [ACR] responder status) with the value of evaluating absolute disease activity states (e.g., remission). METHODS: We pooled data from several recent RA clinical trials and evaluated patients who had completed a 1-year treatment period (n = 629). We compared levels of functional impairment and radiographic progression among patients meeting the ACR 50% or 70% improvement criteria (ACR50 and ACR70 responders, respectively) who attained remission of disease, low disease activity, or moderate disease activity after 1 year, as assessed by the Simplified Disease Activity Index and the Disease Activity Score in 28 joints. RESULTS: Within the ACR50 and ACR70 responder groups, functional disability and radiographic progression were lowest in patients who had attained disease remission at 1 year, compared with those who had attained low or moderate disease activity. When patients attained the same disease activity category, physical function and radiographic progression did not differ significantly with different response states. CONCLUSION: Functional and radiographic outcomes are different in patients depending on the disease activity category they attain, even if the same level of response (change from baseline) is achieved. Among patients who attain the same disease activity category, the degree of response they experience does not seem to matter. Assessing actual disease activity as well as disease activity states should constitute an integral part of clinical trial data reporting.     

New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier

OBJECTIVE: In a 5-year followup study, we investigated the temporal relationship between development of wrist joint erosions as visualized by magnetic resonance imaging (MRI) versus conventional radiography (CR), in patients with rheumatoid arthritis. We also evaluated the risk of erosive progression on CR associated with the presence of MRI erosions. METHODS: In 10 patients with rheumatoid arthritis, MRI and CR of the dominant wrist were performed annually for 5 years. In each image set, each wrist bone (metacarpal bases, carpal bones, radius, and ulna) was assessed for the absence or presence of bone erosions. RESULTS: Nine bones showed radiographic erosions at baseline. Twenty-seven new radiographic erosions developed during the 5-year followup period. Of these 27 new erosions, 21 were detected 1-5 years earlier by MRI than by CR, 3 were simultaneously detected by both methods, 2 were detected 1-2 years later by MRI than by CR, and 1 erosion (radiographically detected at 5-year followup) was not visualized with MRI. MRI detection of new radiographic erosions preceded CR detection by a median of 2 years. In bones with MRI erosions at baseline, the relative risk of radiographic erosions at 5-year followup was 4.5 (95% confidence interval [95% CI] 2.6-7.6), compared with bones without baseline MRI erosions. If bones with baseline radiographic erosions were excluded from the analysis, the relative risk was 4.1 (95% CI 2.2-7.5). CONCLUSION: Most new radiographic bone erosions (78%) were visualized at least 1 year earlier by MRI than by CR. This illustrates that the information on joint destruction provided by CR is considerably delayed compared with that provided by MRI. A significantly increased risk of progression of radiographic erosion in bones with baseline MRI erosions was observed, demonstrating a prognostic value of MRI with respect to long-term radiographic outcome.     

Ability of hand radiographs to predict a further diagnosis of rheumatoid arthritis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well.     

Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: an investigator-initiated, multicenter, randomized, double-blind, parallel-group, placebo-controlled study

OBJECTIVE: To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect. METHODS: Patients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. RESULTS: At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9 (mean +/- SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group. CONCLUSION: Combined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups.     

Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later.

OBJECTIVE: To determine how well the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 classification criteria for rheumatoid arthritis (RA), when used at study inclusion in a cohort of 270 patients with early (<1 year) arthritis, predicted a diagnosis of RA 2 years later and how well they classified these patients at the end of the 2 years. METHODS: Patients were evaluated during 1995-1997 at 7 hospitals in the Brittany region of France. Patients were evaluated at 6-month intervals until November 1999. The diagnosis made by a panel of 5 rheumatologists (P5R) after the last visit was used as the "gold standard." The ACR 1987 criteria for RA were applied prospectively, without taking into account the initial diagnosis. RESULTS: At the last visit (mean +/- SD followup 29.1 +/- 11.8 months; median 30 months), the P5R diagnosed RA in 98 patients. At the last visit, classification by the ACR criteria was satisfactory, and the combination of an office-based rheumatologist's (OBR's) diagnosis of RA and fulfillment of the ACR criteria was sensitive (87%; 85 of 98 RA patients had both) and highly specific (99%; 170 of 172 non-RA patients did not have both). Application of the criteria at the first visit was of limited value for predicting a diagnosis of RA 2 years later. CONCLUSION: After a 2-year followup, the ACR 1987 classification criteria used in combination with an OBR's diagnosis were effective in distinguishing patients with and without RA. The criteria were not useful for predicting RA in patients with arthritis onset within the previous year. Some patients who met the criteria at baseline and after 2 years did not have RA, suggesting that incorporating exclusion criteria may improve the performance of the ACR criteria when used without taking into account the diagnosis by a rheumatologist, particularly in early arthritis.     

Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study

BACKGROUND: The outcome of undifferentiated arthritis (UA) ranges from remission to rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) classification criteria. OBJECTIVES: To report the outcome of UA after 1 year of follow up and compare the disease course of patients who presented with UA, but evolved into RA within 1 year (UA-RA group), with that of patients who presented with RA fulfilling the ACR criteria (RA-RA group). METHODS: The diagnosis of 330 patients who presented with UA was recorded at 1 year. The UA-RA and RA-RA groups were then followed up for 3 more years. Outcome measurements were radiographic progression, disease activity, and functional capacity. RESULTS: From 330 patients who were diagnosed UA, 91 had evolved into RA at 1 year; 62 patients had presented with RA. No significant differences were detected between the UA-RA and RA-RA groups in median Sharp/van der Heijde score at baseline, radiographic progression rates, disease activity, and functional capacity. However, significantly more disease modifying antirheumatic drugs were prescribed in the RA-RA group. CONCLUSION: The disease outcome of patients who present with UA that evolves into RA within 1 year is the same as that of patients who present with RA as measured by radiographic progression, disease activity, and functional capacity.