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Objectives: To study 10-year outcomes in patients with early seropositive rheumatoid arthritis (RA) whether the outcomes improve over time., Methods: Data of 1754 patients with early RA, diagnosed in 1997-2011 were explored; 66% (n=1151) were seropositive and included in the analyses. Patients were divided into five groups by diagnosis year: 1997-1999, 2000-2002, 2003-2005, 2006-2008 and 2009-2011. Clinical parameters including disease activity and function were compared between the groups., Results: A total of 832 (72%) patients attended the 10-year visit, while 319 did not (e.g. 196 had died and 49 moved). The median (IQR) DAS28 decreased from 2.9 (2.2, 3.7) to 2.3 (1.4, 3.0) (p<0.001) between groups 1997-1999 and 2009-2011. The proportion of patients with 2 or more swollen joints on 46 joint count decreased from 33% to 13%, respectively. Median (IQR) pain decreased from 30 (15, 52) to 25 (6, 51) (p=0.03) and fatigue from 31 (12, 52) to 15 (2, 50) (p=0.012). Median (IQR) dr.global decreased from 20 (5, 40) to 0 (0, 5) p<0.001. The proportion of patients with a HAQ-score of ≤0.5 increased from 39% to 49% (p=0.002). The proportion of patients that had used methotrexate by the 10-year visit increased from 79% to 96% (p<0.001) and the proportion of patients who had used bDMARDs increased from 11% to 28% (p=0.001), respectively., Conclusions: Several clinical outcomes were better in patients who were diagnosed more recently. More intensive use of medications over time might have contributed to these improvements.

Objectives: The classification of seronegative arthritides can be challenging. Our aim was to examine the incidence of SpA diagnosis among patients initially diagnosed as seronegative RA., Methods: Using nationwide Finnish registers from social insurance institutions, we identified all adult patients who were diagnosed with incident seronegative RA [International Classification of Diseases (ICD)-10 code M06] from 1 January 2000 to 31 December 2014. The patients whose diagnoses subsequently changed to the ICD-10 codes of SpA (M07, M45, M46, K50 and K51) were identified in the national care register, until 31 December 2016., Results: A total of 9784 adult seronegative RA patients were identified. Of these, 564 patients had their diagnosis subsequently changed to SpA: 275 (48.7%) patients with PsA, 245 (43.4%) patients with axial SpA and 44 (7.8%) patients with diagnoses related to IBD. The cumulative incidence of SpA diagnoses in 15 years was 10.4% (95% CI 8.9, 12.1) and 8.1% (95% CI 7.1, 9.3) in men and women, respectively., Conclusion: This study calls for vigilance in seronegative RA patients, especially those with more atypical presentations, since the diagnosis could change. The possibility of SpA diagnosis should be considered and specifically looked for, as this could impact on management and response to treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months., Methods: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT00908089)., Results: There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%)., Conclusion: Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.

Objectives: We aimed to characterise the clinical and radiographical phenotype of calcium pyrophosphate dihydrate deposition (CPPD) disease in patients initially diagnosed with seronegative RA, and to increase the awareness that CPPD disease can be falsely diagnosed as seronegative rheumatoid arthritis (RA)., Methods: Altogether 435 early seronegative RA patients were clinically diagnosed in a single rheumatology centre and scheduled for a 10-year follow-up. All clinical data were collected and reviewed. CPPD-related arthritis was suspected if a patient had typical radiographical findings and suitable clinical pattern of CPPD or calcium pyrophosphate crystals were found in the synovial fluid. These patients are the subjects of this study., Results: Among 435 seronegative RA patients, 17 patients (3.9%) (baseline mean age 71.2 years, 82% women) with CPPD disease were identified. CPPD resembling clinical patterns in these patients were: chronic CPP crystal inflammatory arthritis (9 patients), acute CPP crystal arthritis (6 patients) and OA with CPPD (2 patients). All had typical radiographical findings of CPPD: Chondrocalcinosis (CC) of triangular fibrocartilage (17 patients [100%]), CC of knee (9 patients [53%]), CC or narrowing of metacarpophalangeal joints (7 patients [41.2%]), CC of metatarsophalangeal joints (4 patients [23.5%]), CC of symphysis pubis (1 patient [5.8%]), CC of glenohumeral joint (1 patient [5.8%]) and scapholunate advanced collapse (5 patients [29.4%]). None of these patients developed typical RA-like erosions., Conclusions: CPPD disease can mimic seronegative RA at baseline and is important in the differential diagnosis of seronegative arthritis at baseline and during follow-up. The prevalence of CPPD patients in our early seronegative RA patients was 3.9%, the percentage was 7.0% among patients ≥60 years at baseline.

Objective: The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions., Methods: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed., Results: Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74)., Conclusion: In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions., (© 2018, American College of Rheumatology.)

Objectives: To investigate the 10-year clinical course of patients with seronegative arthritis with the emphasis of reclassification of diagnoses when applicable., Methods: A total of 1030 patients including 435 seronegative cases were classified as early RA in 1997-2005 at Jyväskylä Rheumatology Centre and prospectively scheduled for a ten-year follow-up. Clinical data from the follow-up visits and the case-reports until and including the 10-year visit or death, whichever happened earlier, were retrospectively collected and reviewed with re-classification of the cases when applicable. Descriptive statistics were used., Results: Among the 435 seronegative cases (69 % women, baseline mean age was 59 years), 13 (13/435 [3%]) could be reclassified as seropositive or erosive RA: 4 turned seropositive (2 for ACPA and 2 for RF [> 2x reference level]) and 9 developed erosions typical for RA. Reclassification revealed 68 (16%) cases of polymyalgia rheumatica, 46 (11%) psoriatic arthritis, 45 (10%) osteoarthritis, 38 (8.7%) spondyloarthritis, 15 (3.4%) plausible reactive arthritis, 10 (2.3%) gout, 17 (3.9%) pseudogout, 6 (1.4%) paraneoplastic arthritis, 6 (1.4%) juvenile arthritis, 2 (0.5%) haemochromatosis, 3 (0.7%) ankylosing spondylitis, 2 (0.5%) giant cell arteritis, and 8 miscellaneous diagnoses. The other 140 patients (32%) could not be reclassified in any clear-cut diagnosis and had features of transient arthritis (n=41), seronegative spondyloarthritis (n=47), while 49 remained unspecified., Conclusions: Over a 10-year follow-up period, reclassification revealed significant heterogeneity in the diagnosis of seronegative RA. Therefore, seronegative arthritis should not be studied as a homogenous entity.

Objective: YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission., Methods: Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay., Results: At the baseline, plasma YKL-40 concentration was 57 ± 37 (mean ± SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment., Conclusions: High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.

Objectives: To study the effects of neglecting intra-articular glucocorticoid injections (IAGCIs) into swollen joints in early rheumatoid arthritis (RA)., Methods: Ninety-nine patients with early, DMARD naive RA were treated, aiming at remission, with methotrexate, sulfasalazine, hydroxychloroquine, low-dose oral prednisolone and, when needed, IAGCIs for 2 years, and randomised to receive infliximab or placebo from weeks 4 to 26. During each of the 15 study visits, patients were scored retrospectively 0.2-0.4 points (depending on the number of non-injected joints) if IAGCIs to all swollen joints were not given. Patients were divided into tertiles by their cumulative scores for neglected injections (CSNI) over 24 months. 28-joint disease activity score (DAS28) area under the curve (AUC) between 0-24 months, remission rates, changes in quality of life, and radiological changes during the follow-up were assessed. Trends across tertiles of CSNI were tested with generalised linear models., Results: Higher CSNI was associated with lower strict remission rates (p=0.005), and lower quality of life (p=0.004) at 24 months, and higher DAS28 AUC (p<0.001) during the follow-up. At 24 months, DAS28 remission rates were 90%, 93% and 76% (p=0.081), and strict remission rates were 74%, 77% and 39% by tertiles of CSNI. No significant differences were observed in radiological progression (p=0.089). IAGCIs were well tolerated., Conclusions: Neglecting IAGCIs into swollen joints is associated with lower remission rates, higher disease activity, and lower quality of life. Hence, IAGCIs should be used as an integral part of the targeted treatment of early RA.

Objectives: To examine gender-related differences in radiographic joint damage in rheumatoid arthritis (RA) using four prospective early RA cohorts., Methods: Radiographs of patients from four early prospective RA cohorts were examined. The extent of joint damage in hands and feet was assessed by three evaluators according to the Larsen score (0-100). Descriptive statistics and two-way bootstrap ANOVA with time as a covariate were employed., Results: A total of 312 patients were included who had at least 15 years of follow up: 68 from the Rheumatism Foundation Hospital in Heinola in the 1970s (Heinola1970), 117 patients from Lund University Hospital in the 1980s, (Lund1980), and 81 and 46 patients from Jyväskylä Central Hospital in the 1980s (JYV1980) and the 1990s (JYV1990), respectively. Median Larsen scores in seropositive women vs. men were 43 vs. 48 (p=0.57), 37 vs. 34 (p=0.25), 31 vs. 9.5 (p=0.008), and 3.0 vs. 4.0 (p=0.34) in the Heinola1970, Lund1980, JYV1980, and JYV1990 cohorts, respectively. The corresponding figures in seronegative women vs. men were 12 vs. 23 (p=0.59), 2.0 vs. 8.0 (p=0.36), and 1.0 vs. 1.5 (p=0.63), in the Lund1980, JYV1980 and JYV1990 cohorts. All Heinola patients were seropositive., Conclusions: After a 15-20 year follow-up period, RA joint damage appears comparable in women and men. The results suggest that management should not differ at least based on gender.

Background: Seronegative rheumatoid arthritis is associated with a milder course of progression compared to seropositive disease. However, long-term follow-up data of the clinical course of seronegative rheumatoid arthritis are sparse. Here we describe four cases with a rare disease entity of aggressive destructive seronegative (rheumatoid) arthritis with 20-35 years of follow-up., Case Presentation: The four cases are women with an initial presentation of seronegative rheumatoid arthritis in 1980-1996 and have received disease-modifying anti-rheumatic drugs since the diagnosis. In all cases, the condition has been refractory to treatments and evolved into a severe disease with destructions of the wrists, sub-talar and ankle joints, as well as large joints but not small joints of fingers and toes. All cases are negative with regard to rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antibodies against carbamylated proteins., Conclusions: This report adds to the existing literature, making the reader aware of this sub-type of inflammatory arthritis which despite being seronegative, can have devastating disease consequences. The report highlights the need for further research into this field in order to better understand this disease sub-type, the pathogenesis, disease course and outcomes.

Objective: We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA)., Methods: Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care., Results: Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36)., Conclusion: Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

Background: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights., Objective: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion., Methods: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived., Results: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10)., Conclusions: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence., Methods: A total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA., Results: Of the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence., Conclusions: Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.

Objective: The objective of this study was to evaluate the long-term safety and efficacy of repeated rituximab (RTX) infusions in the treatment of rheumatoid arthritis in daily clinical practice in Finland., Methods: Data were collected from the medical records of a total of 151 patients with rheumatoid arthritis treated with RTX and followed up for at least 12 months after the treatment onset. Change in the 28-joint Disease Activity Score (DAS28), European League Against Rheumatism response criteria and proportions of patients reaching disease remission (DAS28 < 2.6) or low disease activity (DAS28 < 3.2) were used to assess the clinical response., Results: Of the 151 patients 128 received 2 courses, 76 received 3 courses, and 42 received 4 courses of RTX. The mean time to retreatment for the first 4 courses varied between 11 and 13 months. Median DAS28 decreased from 5.4 (0.5-8.6) to 3.3 (0.6-6.6) after the first course. After the second treatment course, the DAS28 was 3.1 (range, 0.1-6.5). The median precourse baseline DAS28 before the second and third courses were 4.6 (range, 1.7-7.8) and 4.24 (range, 1.7-7.2), respectively. The number of previously failed tumor necrosis factor inhibitors did not predict response to RTX in this patient cohort with extensive use of previous disease-modifying antirheumatic drugs (median = 6)., Conclusions: The treatment as-needed regimen used in this study cohort led to delayed RTX retreatment and disease flare in a significant proportion of patients. A regular retreatment every 6 months, at least, after the first 2 treatment courses in patients who are not in remission could allow better control of disease activity.

Objective: With modern initial aggressive combination treatments with synthetic disease-modifying antirheumatic drugs (sDMARD), most patients with rheumatoid arthritis (RA) achieve remission, have marginal radiographic progression, and sustain normal function. Here we aim to identify the patients failing these targets even after aggressive treatment., Methods: Ninety-nine patients with early, active RA were treated with a combination of 3 sDMARD and prednisolone (PRD), and either infliximab or placebo infusions during the first 6 months, aiming at strict remission. After 24 months, the treatments became unrestricted. At 60 months, 4 evident clinical features of treatment failure were defined: area under curve (AUC) between 6-60 months for disease activity score assessing 28 joints > 2.6; AUC 6-60 for health assessment questionnaire > 0.5; progression in total Sharp/van der Heijde score 0-60 months > 3 units; and need of PRD or biologic DMARD treatment at 60 months., Results: A total of 93 patients were followed up for 60 months. Of them, 45 had no features of treatment failure, 30 had 1, 10 had 2, 7 had 3, and 1 patient had all 4 features. Having 2-4 features of treatment failure at 5 years was predicted by the health assessment score at baseline, and by even low residual disease activity at 3 and 6 months., Conclusions: Only 20% of the patients with RA treated early with combination sDMARD and PRD have more than 1 clinical feature of treatment failure at 60 months. Residual clinical disease activity at 3-6 months was the most important predictor for identifying these patients. The study was registered at www.clintrials.gov (NCT00908089).

Objective: To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA)., Methods: Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed., Results: Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13)., Conclusions: In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Early treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome., Methods: 99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26., Results: At 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058)., Conclusions: Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.

Background: The new 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) aim at earlier diagnosis of RA compared to the 1987 ACR criteria., Objective: To evaluate the ability of the 2010 ACR/EULAR and the 1987 ACR classification criteria to predict radiographic progression after 10 years of follow-up., Methods: All early arthritis patients referred to Central Hospital in Jyväskylä from 1997 to 1999 (cases with peripheral joint synovitis, other specific diseases excluded) were included in this 10-year follow-up study. Radiographs of hands and feet were analysed according to Larsen on a scale of 0-100., Results: At 10 years, 58% of the patients had an erosive disease (defined as Larsen ≥2 in at least one joint). The discriminative power of the 2010 ACR/EULAR and the 1987 ACR criteria (erosive disease at 10 years) were comparable, with area under the curve 0.72 (95% CI 0.65 to 0.79) (2010 ACR/EULAR criteria) and 0.65 (95% CI 0.58 to 0.72) (1987 ACR criteria). The respective sensitivities and specificities were 0.87 and 0.70, and 0.44 and 0.47. At 10 years, median (IQR) Larsen score was 6 (0, 15) among patients who had fulfilled both sets of criteria, 2 (0, 8) in those who met the 2010 ACR/EULAR and did not meet the ACR 1987 criteria, 0 (0, 5) in those who met ACR 1987 criteria but did not meet 2010 ACR/EULAR criteria, and 0 (0, 2) among patients who did not fulfil either of the criteria. The percentage of patients with erosions was 69%, 64%, 32% and 26%, respectively., Conclusions: The ability of the 2010 ACR/EULAR and 1987 ACR classification criteria to identify erosive disease in early arthritis is low. The discriminative power of the 2010 ACR/EULAR criteria of erosiveness in 10 years is slightly better than that of the 1987 ACR criteria.

Objectives: Selection of efficacious medications for rheumatoid arthritis (RA) has tremendously increased over a decade including new costly biologic agents and inexpensive conventional anti-rheumatic drugs, used in combinations for more efficacy. Treatments aim at remission or at least low disease activity. Our objective was to study whether treatment target is reached and to what cost, in patients with RA in two Nordic rheumatology clinics., Methods: Cross sectional observational clinical data of all patients with RA seen in 2010 in two Nordic county hospital rheumatology units: Kristiansand, Norway and Jyväskylä, Finland, which both serve a population of about 275,000. Measures included patient demographic measures, clinical characteristics, disease activity, functional status, and treatments. Annual costs of medications to the society were calculated per 100 patients, using an assumption that a patient is taking current medications for one year., Results: Patient populations from Kristiansand and Jyväskylä were similar according to age, gender, disease duration, and prevalence of RF and CCP. Disease activity was low and patients' functional status well reserved in both clinics. Almost twice as many patients in Kristiansand than in Jyväskylä (33% vs. 17%) used biologic agents. A combination of conventional anti-rheumatic drugs was currently used by <1% of patients in Kristiansand and by 37% of patients in Jyväskylä. Estimated annual costs of medications per 100 patients were €508,000 in Kristiansand and €280,000 in Jyväskylä., Conclusions: Treatment target of remission/low disease activity and good functional status can be reached in RA using expensive and less-expensive anti-rheumatic drugs.

The Finnish Rheumatoid Arthritis Combination Therapy Trial (FIN-RACo) started in 1993, in an era of disappointing results in the treatment of rheumatoid arthritis (RA). The FIN-RACo was the first trial aiming at remission and comparing two different treatment strategies: initially triple therapy with compulsory prednisolone (FIN-RACo strategy), or monotherapy with optional prednisolone (SINGLE strategy). The results at 2, 5 and at 11 years are in favour of the initial FIN-RACo strategy without an increase in adversities. Nevertheless, with targeted treatment, even the SINGLE strategy group patients show low disease activity and moderate radiographic progression. Most leading Finnish rheumatologists participated in the FIN-RACo trial and have become convinced of the excellent results, good safety, and feasible administration of the FIN-RACo strategy. They have thus adopted it in real life and tutored the next generation to do the same. This has undoubtedly affected the Finnish approach to treating early RA; the Finnish Current Care Guideline recommends the FIN-RACo combination as the first treatment choice in early, active RA. As a consequence, the use of biologics in early RA is less frequent in Finland compared to many countries. Simultaneously, however, at least one hard outcome of RA, work disability, has decreased.

Objectives: To assess long-term impact of RA on the HR-QoL in a cohort of working-age patients with early disease treated by a multidisciplinary team including early and active use of disease-modifying anti-rheumatic drugs (DMARDs)., Methods: Fifty-five consecutive patients with RA who were naïve to DMARDs and glucocorticoids were assessed at baseline and at 6 months, 1, 2, 5 and 10 years. HR-QoL, disease activity, function, and joint destruction of hands and feet were assessed by using the Nottingham Health Profile (NHP) instrument, the 28-joint based Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and the Larsen scores, respectively. GEE (generalised estimation equations)-method was used to evaluate longitudinal relationships between the HR-QoL changes and other variables., Results: All NHP dimensions except social isolation improved significantly during the first six months and remained favourable up to 10 years. The most prominent improvements were seen in the dimensions for pain and emotional reaction (p<0.001). In longitudinal evaluation statistically significant associations (p<0.001) were found between the DAS28 and the NHP dimensions for pain, energy and emotional reaction, and between the HAQ and the NHP dimensions for pain, energy and mobility. The extent of joint damage had no statistically significant associations to the six dimensions of the NHP instrument., Conclusions: Early improvements in HR-QoL carried over the ten-year follow-up in patients with recent-onset RA treated with a multidisciplinary strategy including early and active DMARD therapy. HR-QoL changes were longitudinally associated especially with disease activity and function.

Introduction: Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD., Methods: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years., Results: Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P=0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years., Conclusions: Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy., Trial Registration: Current Controlled Trials ISRCTN18445519.

Objective: To study longterm outcomes of 60 patients with palindromic rheumatism (PR) diagnosed in 1967-1984., Methods: A cohort of patients with PR was identified in Jyväskylä Central Hospital in 1967-84, and reexamined in 1984-86. In 2006, medical records of the patients were reviewed to analyze the proportion of patients who had developed chronic rheumatoid arthritis (RA), had joint replacement surgery, or had died. Patients' health status was reviewed by mail questionnaires including functional status on the Health Assessment Questionnaire (HAQ), pain, and the number of painful joints., Results: Forty patients developed chronic RA over the observation period of over 20 years, among whom 38 patients within 10 years and 2 patients after 10 years. Twenty-four patients had died by 2006, 17 (42%) in the RA group and 7 (35%) in the non-RA group. Nine patients, all in the RA group (23%), had received 1 or more joint replacements. The mean HAQ score was 0.57 in the non-RA survivors (mean age 70 yrs), compared to 0.89 in the RA group (mean age 66 yrs) (p = 0.020, adjusted for age). Pain scores and the number of painful joints were similar between the groups., Conclusion: Two-thirds of the patients with PR developed chronic arthritis. The risk to develop chronic arthritis remained over 10 years. The RA group was characterized with functional declines and having joint replacements as longterm outcomes of the disease.

Objective: To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD., Methods: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission., Results: At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively., Conclusion: Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.

Objective: To evaluate the 5-year incidence of cervical spine disorders in patients with early rheumatoid arthritis (RA) treated by 2 different disease modifying antirheumatic drug (DMARD) strategies., Methods: In a national, multicenter, prospective FIN-RACo-trial, a cohort of 199 patients with early, clinically active RA was randomly assigned to treatment with a combination of 3 DMARD and prednisolone (Combi group) or with a single DMARD (Single group) with or without prednisolone, aiming to induce remission. After 2 years, the DMARD therapy was unrestricted. Lateral view cervical spine radiographs during full flexion and extension were taken at the 5-year followup visits. The presence of anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI), and subaxial subluxation (SAS) was assessed in the 149 patients with radiographs available (80 Single and 69 Combi)., Results: At the 5-year visits, aAAS, AAI, and SAS were found in 13 (9%), 6 (4%), and 9 (6%) patients, respectively. The corresponding Single/Combi group ratios were 11/2, 5/1, and 5/4. Of the baseline data, only poor physical function [Health Assessment Questionnaire (HAQ); p = 0.024] and Single treatment strategy (p = 0.019) were significantly associated with aAAS. Worse HAQ scores and Disease Activity Score 28 values were found in patients who developed aAAS during the 5-year followup., Conclusion: RA patients with sustained clinical disease activity and poor HAQ are at increased risk of developing aAAS. The development of aAAS during the first 5 years of RA was rare among the patients treated with a combination of DMARD for at least 2 years from the diagnosis. Intensive treatment with traditional DMARD prevents or retards the development of aAAS in patients with recent-onset RA.

Objective: To assess disability and functioning of elderly patients with rheumatoid arthritis (RA) and population controls by linking the items included in the self-report Multidimensional Health Assessment Questionnaire (MDHAQ) with components of the WHO International Classification of Functioning, Disability and Health (ICF) instrument., Methods: In total, 1439 patients with RA (mean age 66 yrs, men 29%) and 957 population controls (65 yrs, men 27%) completed a mailed questionnaire. Functioning was recorded by the Finnish version of MDHAQ. Data included comorbidity, subjective health, education level, employment, exercise habits, self-report joint pain/tenderness, and, for patients, the disease duration., Results: Patients had lower levels of functioning compared to controls in all ICF domains, with the exception that male patients functioned comparably to male controls in the "general tasks and demands" domain. In patients, disease activity, education, exercise frequency, and comorbidities were expectedly associated with lower functioning in the body structure and function component, while male sex and subjectively perceived health were associated with more favorable functioning. In the activity and participation components, disease activity, exercise frequency, and comorbidities were associated with impaired functioning, while better health on self-report was associated with better functioning., Conclusion: There is an extra burden of disability in elderly patients with RA compared to the reference population. With a large patient and control population sample, our study shows that use of the self-report MDHAQ identifies all 3 main components of the ICF framework, thus covering a wide spectrum of functioning. Elderly patients with RA, in comparison to population controls, encounter more difficulties in daily activities and their social life.

Anti-citrulline antibodies are highly specific to rheumatoid arthritis (RA) and are thus helpful in differential diagnosis. Early and aggressive disease modifying anti-rheumatic drug (DMARD) therapy is essential for a positive treatment result in cases of RA. Remission during the 1st year of treatment predicts permanent remission, milder joint damage and better functional ability. It is recommended that patients with an unsatisfactory response to DMARDs, including methotrexate and a combination of DMARDs, should be treated primarily with TNF blockers, and non-responders with rituximab or abatacept. RA is an independent risk factor for cardiovascular diseases. The assessment of cardiovascular risk must not be forgotten in daily practice.

Objective: To develop a continuous composite index of disease activity for rheumatoid arthritis (RA) based on the 7 American College of Rheumatology (ACR) core data set of disease activity measures: Mean Overall Index for Rheumatoid Arthritis (MOI-RA)., Methods: The MOI-RA is the mean of standardized values of tender and swollen joint counts (28, 42, or 66/68 joint counts), physical function (Health Assessment Questionnaire 0-3), patient's and physician's assessments of global health and patient's assessment of pain (visual analog scale 0-100 mm) and erythrocyte sedimentation rate (1-100). All the 7 components were standardized (0-100), and the mean of standardized values was calculated. The range of MOI-RA is 0-100; higher values indicate poorer outcomes. The validity and measurement properties of MOI-RA were analyzed in 169 patients in the Finnish RA Combination therapy trial., Results: The mean MOI-RA28 decreased from 38.5 to 13.3 [standardized response mean (SRM) = 1.8, effect size (ES) = 1.9] from baseline to 6 months, compared to Disease Activity Score (DAS) 28, which decreased from 5.55 to 2.77 (SRM = 2.0, ES = 2.8). Correlation between MOI-RA28 and DAS28 was 0.90. When compared to the ACR response categories (20/50/ACR remission), changes in MOI-RA versions (using 28/42/66 joints) were similar. The reproducibility of MOI-RA with different joint counts was 0.97. A simulation in which 15% of the component values of MOI-RA were randomly omitted indicated an intraclass correlation coefficient of 0.98 between incomplete and complete data., Conclusion: MOI-RA is a simple and feasible index based on the ACR core data set of disease activity measures for assessment of disease activity and treatment response in RA trials and clinical settings.

Objective: To examine the influence of components of the Disease Activity Score 28 (DAS28) [tender joint count (TJC), swollen joint count (SJC), patient's general health (GH), and erythrocyte sedimentation rate (ESR)] on the total DAS28 score, and overlapping of the 4 individual components in rheumatoid arthritis (RA) patients with low, moderate, or high disease activity., Methods: The effect of each component was studied in the FIN-RACo trial patients at 6 months and in a "theoretical model," where each component of the DAS28 ranged as follows: TJC and SJC from 0 to 28, GH from 0 to 100, and ESR from 1 to 100, while the other 3 components were 0 (ESR1). Overlapping of the components was studied in the FIN-RACo trial patients at 6 months with low (DAS28 < or = 3.2), moderate (DAS28 > 3.2 and < or = 5.1), and high (DAS28 > 5.1) disease activity. The higher limit for overlapping was defined as the highest SJC in the low disease activity group, and the lower limit as the lowest SJC in the high disease activity group; the percentage of patients who fall between these limits represent overlapping in SJC. Overlapping was calculated similarly concerning TJC, ESR, and GH., Results: ESR had the greatest effect on DAS28, followed by TJC, GH, and SJC, while in the "theoretical model" TJC had the greatest effect on the DAS28, followed by ESR, SJC, and GH. At 6 months, overlapping was present in 54%, 45%, 49%, and 31% of patients in SJC, TJC, GH, and ESR, respectively., Conclusion: In real-life patients, ESR had the greatest effect of the 4 components of DAS28 on the total DAS28 score. The values of the individual components of DAS28 overlap considerably among the 3 disease activity groups.

Background: Total joint replacement (TJR) surgery is an important severe long-term outcome of rheumatoid arthritis, but relatively little is known about changes of its incidence in patients with rheumatoid arthritis over the past two decades., Methods: A population-based, retrospective, incidence case review was conducted to analyse the frequency of primary TJR surgery of the knee and hip in all patients, and specifically in patients with rheumatoid arthritis in Central Finland between 1986 and 2003. Patients with TJR surgery of the knee and hip were identified in hospital databases over the 18-year period. Age-standardised incidence rate ratios for the primary TJR of the knee and hip were calculated, stratified to sex and diagnosis, with 1986 as the reference value., Results: In patients without rheumatoid arthritis the age-adjusted incidence rate ratios (with 95% CI) for TJR of the knee increased 9.8-fold from 1986 to 2003 in women and men, and for TJR of the hip 1.8-fold in women and 2-fold in men. By contrast, no meaningful change was seen over this period, in age-adjusted incidence rate ratios for TJR of the knee or hip in patients with rheumatoid arthritis, ranging from 0.7 to 1.2 in 2003 compared with 1986., Conclusion: The prevalence of TJR surgery has increased 2-10-fold in patients without rheumatoid arthritis patients, associated with an ageing population, but has not increased in patients with rheumatoid arthritis between 1986 and 2003. These data are consistent with emerging evidence that long-term outcomes of rheumatoid arthritis have improved substantially, even before the availability of biological agents.

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.

Objective: To determine whether early inflammatory activity in the first year of disease compared to persistent or later occurrence of swelling or tenderness in the wrist joints is associated with 5-year erosions in the same joint in patients with early rheumatoid arthritis (RA)., Methods: A cohort of 195 patients with early active RA was enrolled in the Finnish RA Combination Trial. Swelling and tenderness of wrists were assessed at baseline and at 3, 6, 12, 24, 36, and 48 months. Radiographs of the wrists were taken at the baseline and at 5 years. The 237 wrist joints of 125 patients without erosions at baseline were classified according to wrist swelling, i.e., I: never swollen; II: swollen during first year only; III: swollen during the second to fourth year only; and IV: swollen during the first year and followup, and similarly according to tenderness., Results: Thirty percent of the wrists were never swollen in all clinical examinations; 43% were swollen only during the first year; 11% were not swollen in the first year, but were swollen at some time during 24-48 months; and 16% of wrists were swollen during the first year and at some time during 24-48 months. At 5 years, 64% of 237 wrists remained free of erosions. Erosions developed in 82% of wrists that were swollen during both the first year and 24-48 months, versus 56% of wrists that were not swollen at first year but were swollen during 24-48 months, 31% of wrists that were swollen during the first year only, and 11% of wrists that were never swollen. Similar results were seen for joint tenderness., Conclusion: Wrist swelling during the first year only is associated with less future wrist radiographic damage than persistent swelling or swelling only during the followup. Our results emphasize the value of early and continuous suppression of inflammatory activity in early RA.

Objective: To analyze longitudinal data over 5 years for changes in Health Assessment Questionnaire (HAQ) scores in patients with rheumatoid arthritis (RA) and age- and sex-matched controls from the general population., Methods: In 2000 and 2005, identical self-report questionnaires were mailed to a cohort of patients with RA and control cohort from the community. The questionnaire included the HAQ, which was used to assess functional status. Changes in HAQ scores over 5 years were analyzed., Results: In 2000, 73% of 1,495 patients with RA and 77% of 2,000 general population controls responded to the questionnaire. In 2005, 84% of 2,022 patients with RA and 77% of 1,817 controls responded. A total of 863 patients with RA and 1,176 community controls responded in both 2000 and 2005 and were included in the analyses. Mean baseline HAQ scores were significantly higher in patients with RA than in controls (0.71 versus 0.17; P < 0.001). Over 5 years, the HAQ scores increased by 0.01 units per year in both the RA cohort and the community population; in both cohorts, the net change was primarily attributable to individuals over age 70 years. Changes in HAQ scores were similar in patients and controls who had low HAQ scores at baseline. Female patients with baseline HAQ scores of >or=0.5 had less potential for improvement than did controls. Among subjects in both groups who had HAQ scores >2, death was a common outcome over the next 5 years., Conclusion: Currently, progression of functional disability among patients with RA and among persons in the general population is largely explained by the aging process. Our results showing stable function scores over 5 years in most patients with RA who are younger than age 70 years provide further evidence of improved status of RA patients today compared with the major declines observed in previous decades.

Objective: To compare neck muscle strength and mobility of the cervical spine in rheumatoid arthritis (RA) patients with and without atlantoaxial (AA) disorders (anterior atlantoaxial subluxation [AAS], AA impaction)., Design: Clinical cross-sectional study., Setting: Outpatient rheumatology and rehabilitation clinics in a Finnish hospital., Participants: Patients with RA (N=124; mean age +/- standard deviation, 62+/-12y [corrected]) on a waiting list for orthopedic surgery. Thirty (24%) patients presented with AA disorders (16 with anterior AAS, 8 with AA impaction, 6 with a combination of anterior AAS and AA impaction)., Interventions: Not applicable., Main Outcome Measures: Neck function was measured by isometric neck strength and mobility tests, neck pain by a visual analog scale, erosion of the hands and feet by radiography, and the patients' function by the Health Assessment Questionnaire (HAQ)., Results: Maximal neck muscle strength against flexion, extension, and rotation was lower in patients with AA disorders compared with the other patients in both women (P=.012) and men (P=.017). Mobility was lowest in the AA impaction group in all measured directions (P<.001). Peripheral erosive disease was more frequent in the group with AA disorders. They also had longer disease duration and were more disabled (HAQ) than the other patients., Conclusions: Neck muscle strength is significantly decreased in patients with AA disorders. Mobility of the cervical spine is most limited in patients with AA impaction, but can be normal in cases with solitary anterior AAS.

Objective: To determine whether nonresponse to a mailed health survey predicts mortality in patients with rheumatoid arthritis (RA) and in a community sample in Finland., Methods: A 5-page health questionnaire was administered in 2000. Two years later the vital status of the subjects was ascertained from the Population Registry., Results: A total of 1095 (73%) patients with RA and 1530 (77%) community control subjects returned a completed questionnaire. Over the 2-year period, the number of deaths was 57 (5.2%) in RA responders and 37 (9.3%) in RA nonresponders (p = 0.004). The corresponding figures in community controls were 34 (2.2%) and 23 (4.9%) (p = 0.002). In a Cox regression model adjusted for age and sex, RA patient and community control nonresponders were respectively 1.65 (95% CI 1.07 to 2.55) and 2.89 (95% CI 1.69 to 4.94) times more likely to die over the 2 years compared to the responders., Conclusion: Nonresponders to a mailed health survey were more likely to die over 2 years compared to responders. The possible nonresponse bias should be kept in mind in the interpretation of the results of studies that are based on mail questionnaires only.

Objective: To study the frequency of remission using 3 sets of criteria in patients with rheumatoid arthritis (RA) at 5 years after the diagnosis., Methods: All adult patients with recent onset inflammatory arthritis who did not meet criteria or show clinical signs of other specific arthritides were included in the RA1997 inception cohort at Jyväskylä Central Hospital, Finland, and were assessed for remission at 5-year control examination. Remission was defined as (1) American College of Rheumatology (ACR) remission (fatigue excluded), (2) clinical remission with no tender and no swollen joints and normal erythrocyte sedimentation rate, and (3) radiographic remission with no worsening of erosions and no new erosions from baseline to 5 years., Results: The study included 127 patients with early RA (mean age 56 yrs, 61% female, 54% with positive rheumatoid factor, and 25% with erosions). At 5 years, 111 patients were examined, 17% (95% CI 11%-25%) of whom met ACR remission criteria, 37% (95% CI 28%-47%) met clinical remission criteria, and 55% (95% CI 49%-68%) met radiographic remission criteria. Only 13 (12%) patients met all 3 sets of remission criteria. The rate of remission was statistically significantly different (p < 0.001) using the 3 sets., Conclusion: The rate of remission in RA depends on the criteria used. No gold standard exists for defining remission in RA. A set of criteria including no sign of inflammatory activity and no radiographic progression might be a basis for development of clinically relevant remission criteria for RA.

Objective: To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA)., Methods: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomized to receive either a combination of disease-modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5-year followup, the cumulative number of days of sick leave and RA-related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline., Results: Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient-year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0-3), 4 (IQR 0-131), 16 (IQR 0-170), and 352 (16-365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5-year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%)., Conclusion: Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.

Objective: To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD., Methods: In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score., Results: A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively., Conclusion: Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.

Objective: There is a common impression, rarely documented, that the outlook of patients with rheumatoid arthritis (RA) is different today compared to previous decades. We investigated the 5-year radiographic progression of 3 cohorts of patients with early RA enrolled in the 1980s and 1990s., Methods: Patients with early RA were enrolled into 3 separate studies in 1983-85 (n = 58; Cohort A), 1988-89 (n = 77; Cohort B), and 1995-96 (n = 62; Cohort C) at one rheumatology center; all were subsequently treated actively with disease-modifying antirheumatic drugs according to the "sawtooth strategy" to control inflammation, and monitored regularly to collect data for evaluation of longterm outcome. Evaluation over 5 years included disease activity measures and medications. Radiographs of hands and feet taken at baseline and at 2 and 5 years were analyzed by Larsen score (0-100)., Results: Larsen score increased by a median of 12, 6, and 4 points by Year 5 in cohorts A, B, and C, respectively (p = 0.001), adjusted for age, sex, rheumatoid factor (+/-), and the baseline values for Larsen score and erythrocyte sedimentation rate. RF positivity and persistent high disease activity over 5 years were associated with greater progression of radiographic damage., Conclusion: Radiographic progression was greatest in the earliest cohort and mildest in the most recent cohort, a phenomenon that was also seen in the literature review. The reasons for the observation may include (1) improved therapy, (2) milder disease, and (3) patient selection.

Objective: To evaluate the impact of a 2-year home-based strength-training program on physical function in patients with early rheumatoid arthritis (RA) after a subsequent 3-year followup., Methods: Seventy patients with early RA were randomized to perform either strength training (experimental group [EG]) or range-of-motion exercises (control group [CG]). Maximal strength values were recorded by dynamometers. The Modified Disease Activity Score (DAS28), pain, Health Assessment Questionnaire (HAQ), walking speed, and stair-climbing speed were also measured., Results: The maximum strength of assessed muscle groups increased by 19-59% in the EG during the training period and remained at the reached level throughout the subsequent 3 years. Muscle strength improved in the CG by 1-31%, but less compared with the EG. During the 2-year training period, DAS28 decreased by 50% and 45% and pain by 67% and 39% in the EG and CG, respectively. The differences in muscle strength, DAS28, and HAQ were significantly in favor of the EG both at the 2-year and 5-year followup assessments., Conclusions: The improvements achieved during the 2-year strength-training period were sustained for 3 years in patients with early RA.

Objective: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA)., Methods: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age., Results: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods

Objective: To study whether clinically observed tenderness and/or swelling of a wrist joint over the first 3 years after diagnosis predict the development of erosions in radiographs of the same joint at 5 years in patients with early rheumatoid arthritis (RA)., Methods: A total of 58 patients with recent onset RA were enrolled in a prospective RA study at Jyväskylä Central Hospital in 1983-85. Physical examination including joint counts was performed 6 times over 3 years (at 0, 6, 12, 18, 24, and 36 mo). Radiographs of hands and feet taken at the 5-year visit were scored according to the Larsen method (0-1 = non-erosive; 2-5 = erosive). At each visit, the wrist joints were assessed for tenderness (0/1) and swelling (0/1). A frequency (ranging from 0 to 6) was calculated for 4 inflammation categories tenderness, swelling, tenderness or swelling, and tenderness and swelling over the 3 years. Percentages of wrist joints with erosions on the 5-year radiographs were calculated for the frequency groups 0, 1, 2-3, and 4-6 of each category. Two patients died, and 5 wrists were erosive at baseline. Thus the data for 107 wrist joints of 54 patients were available for analyses., Results: A statistically significant correlation was seen in the frequency of clinical inflammation and the development of erosions. Only one (3.3%) wrist with no tenderness in 6 examinations over the first 3 years developed erosions over 5 years, while 13 (59.1%) wrists that were tender 4-6 times in 6 examinations developed erosions. The corresponding percentages were 4.4% and 50.0% for wrists with swelling, 3.4% and 51.6% for wrists with tenderness or swelling, and 6.1% and 75.0% for wrists with tenderness and swelling., Conclusion: Radiographic erosions develop rarely without preceding clinically detectable inflammation in the joints of patients with early RA.

Objective: To study the prevalence of cervical spine subluxations and predictive factors for atlantoaxial subluxations (including anterior atlantoaxial subluxation and atlantoaxial impaction, i.e., vertical subluxation) in patients with rheumatoid arthritis (RA) who were treated early and continuously with disease-modifying antirheumatic drugs for 8-13 years., Methods: Radiographs of the cervical spine were obtained in 103 of 110 patients (the 110 surviving patients of the original 135-patient cohort) at their 8-13-year followup visits. The prevalence of cervical spine subluxations was determined. Demographic variables and the first 5-year serial data concerning disease course were analyzed in a logistic regression model to find predictive factors for atlantoaxial subluxations., Results: Atlantoaxial subluxations were found in 14 patients (14%), and 5 patients (5%) had subaxial subluxations. Older age at baseline, greater disease activity during the first 5 years, and early erosiveness in peripheral joints predicted the development of atlantoaxial subluxations. Patients who had >or=10% of the maximum possible radiographic damage (by Larsen score) in peripheral joints at 5 years were 15.9 times more likely to develop atlantoaxial subluxations at 8-13 years than patients whose peripheral joint damage remained <10% of the maximum., Conclusion: Compared with historical control RA cohorts, a lower prevalence of cervical spine destruction was found in the present group of patients. Rapid erosiveness in peripheral joints was the best predictor for atlantoaxial subluxations. Extensive erosiveness in peripheral joints should alert rheumatologists to the possible development of atlantoaxial subluxations in patients with RA.

Objective: To study the impact of 24 months of strength training on the physical function of patients with early rheumatoid arthritis (RA)., Methods: Seventy patients were assigned to either the strength training (experimental) group (n = 35) or the control group (n = 35). Patients in the experimental group performed strength training for 24 months, and control patients were instructed to perform range of motion exercises. Maximal strength of the knee extensors, trunk flexors, and extensors, as well as grip strength were recorded with dynamometers. Disease activity was assessed by the erythrocyte sedimentation rate and Ritchie's articular index, joint damage was determined by the Larsen x-ray index, and functional capacity was assessed using the Valpar 9 test and the Stanford Health Assessment Questionnaire (HAQ). The employment status of each patient was recorded., Results: In the experimental group, strength training led to significant increases (19-59%) in maximal strength of the trained muscles. Such increases in the control group varied from 1% to 31%. There was a clear training effect on muscular strength in favor of the experimental group, but significant improvements in the HAQ indices as well as in the Valpar 9 test were seen also in control patients. Results of the Valpar 9 and the HAQ were statistically significantly better in patients who remained gainfully employed compared with patients who retired preterm during followup. However, compared with patients who remained in the work force, patients who retired were older, and their work was physically more demanding., Conclusion: As expected, strength training led to increased muscle strength, but this increase did not correlate with improved physical function as assessed by the Valpar 9 work sample test. The increased muscle performance did not prevent a substantial proportion of patients from retiring preterm. The 2 items from the Valpar 9 test that were applied were not sensitive enough to differentiate the patients according to their working status.

The present case-control study was conducted to investigate the relationship between smoking and rheumatoid arthritis, and to investigate formally the interaction between sex, smoking, and risk for developing rheumatoid arthritis. The study was performed in the Central District of Finland. Cases were patients with rheumatoid arthritis and the control group was a random sample of the general population. Logistic regression models were used to evaluate the effect of smoking on risk for rheumatoid arthritis, after adjusting for the effects of age, education, body mass index, and indices of general health and pain. Overall, 1095 patients with rheumatoid arthritis and 1530 control individuals were included. Patients were older, less well educated, more disabled, and had poorer levels of general health as compared with control individuals (all P < 0.01). Preliminary analyses revealed the presence of substantial statistical interaction between smoking and sex (P < 0.001). In separate multivariable analyses, past history of smoking was associated with increased risk for rheumatoid arthritis overall in men (odds ratio 2.0, 95% confidence interval 1.2-3.2) but not in women. Among men, this effect was seen only for rheumatoid factor-positive rheumatoid arthritis. There were significant interactions between smoking and age among women but not among men. We conclude that sex is a biologic effect modifier in the association between smoking and rheumatoid arthritis. The role of menopause in the etiology of rheumatoid arthritis merits further research.

Objective: To compare Health Assessment Questionnaire (HAQ) scores of patients with rheumatoid arthritis (RA) with HAQ scores from a sex- and age-adjusted population., Methods: Patients with RA (n = 1,095) and control subjects (n = 1,530) completed a mailed questionnaire that comprised the HAQ, pain and global health scores, education level, and comorbidities, as well as height, weight, and lifestyle attitudes, including smoking and exercise habits., Results: The HAQ scores increased (indicating declining function) with older age in patients and controls. The HAQ scores were above the reference values (>95th percentile of the HAQ scores of the age- and sex-matched population) in 17-45% of women with RA and in 7-32% of men with RA ages 30-79 years, while the HAQ scores of the patients > or =80 years were similar to those of the age- and sex-matched population. In a logistic regression model, the odds ratio for disability (HAQ score > or =1; at least some difficulties in most activities of daily living) was 7.7 (95% confidence interval 5.3-11.1; P < 0.001) among patients with RA compared with community controls, when adjusted for age, sex, education, smoking, exercise, body mass index, number of comorbidities, and pain., Conclusion: RA is associated with a >7-fold risk of disability compared with that in a general population of adults in the same community. The impact of disability due to RA appears to be greater in younger and middle-age people than in elderly patients.