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M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 37 records · Page 2Linked to original sources

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC.

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci ( approximately 200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1(*)030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1(*)030101 and DRB1(*)08 and (*)11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1(*)08 and (*)11 (P<0.000003) and DPB1(*)030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cellular and humoral markers of systemic inflammation in acute reactive arthritis and early rheumatoid arthritis.

OBJECTIVE: To compare systemic inflammation in reactive arthritis (ReA), rheumatoid arthritis (RA), and sepsis using novel markers of systemic inflammation, and to study whether they are helpful in distinguishing between ReA and RA. METHODS: In 28 patients with acute ReA, 16 patients with early untreated RA, and 25 patients with blood culture-positive sepsis, phagocyte CD 11b expression was measured by flow cytometry, serum procalcitonin (PCT) levels by immunoluminometric assay, and soluble E-selectin (sE-selectin) levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Neutrophil and monocyte CD11b expression and serum levels of PCT and sE-selectin were higher in patients with sepsis than patients with ReA or RA, or in healthy subjects (all p < 0.01). They were comparable in healthy subjects, ReA, and RA. CONCLUSION: Patients with acute ReA and early RA have normal CD11b expression levels on phagocytes and normal PCT and sE-selectin levels in serum. Elevated levels suggest possible sepsis.

Acute Disease↗

HLA-DRB1* alleles and temporomandibular joint erosion in patients with various rheumatic diseases.

OBJECTIVE: To investigate the association between HLA antigens and temporomandibular joint (TMJ) erosion, salivary composition, and focal sialadenitis in patients with rheumatic diseases. METHODS: Eighty-four patients, 24 with rheumatoid arthritis (RA), 19 with mixed connective tissue disease (MCTD), 19 with ankylosing spondylitis (AS), and 22 with spondyloarthropathy (SPA) were studied. Each patient underwent clinical examination of the masticatory system, unstimulated and stimulated saliva collection, and minor salivary gland biopsy. Radiographs (OPTG) of the TMJ were obtained, and HLA allele (A, B, C and DRB1*) analysis was performed. Erosion in OPTG was scored from 0 (no erosion) to 4 (condyles totally eroded). In the analysis, scores 0-2 were grouped as normal or mild changes, and scores 3-4 as distinct erosions. One hundred healthy blood donors served as controls for HLA typing. RESULTS: Distinct erosion of the TMJ in OPTG was observed in 22 (27%) patients. It affected four (17%) of the 24 patients with RA, three (17%) of the 18 with MCTD, seven (37%) of the 19 patients with AS and eight (38%) of the 21 with SPA non-significant (NS). The mean erosion scores were 1.7 for RA, 1.3 for MCTD, 2.5 for SPA, and 1.6 for AS patients [probability (p) = 0.04]. The frequency of HLA-B27 antigen was higher in the AS and SPA patients, and that of HLA-DRB1*04 allele higher in RA patients than in control subjects. In the whole patient population, HLA-DRB1*01 allele was significantly associated with erosions 16/36 (44%) versus 6/46 (131%1) (p = 0.0014). In the SPA group, patients with HLA-DRBI*01 allele had a significantly higher occurrence of distinct erosions than patients without this allele [8/10 (80%) versus 0/11 (0%) (p = 0.0002)], whereas DRB1*06 was protective [0/8 (0%) versus 8/13 (62%) (p = 0.018)]. HLA-DRB1*04 was associated with increased salivary IgG in the RA patients. CONCLUSION: HLA antigens are significantly associated with the development of destructive lesions in the TMJ, as well as composition of saliva in patients with various rheumatic diseases.

Alleles↗

Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity.

OBJECTIVE: To measure serum levels of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and serum cartilage oligomeric matrix protein (COMP) in patients with early joint inflammation, and to study the correlation of these two tests with clinical measurements. METHODS: Adult patients with recent-onset arthritis, of <3 months' duration, were referred from primary healthcare centres to rheumatologists. Serum levels of anti-CCP antibodies and COMP at baseline were analysed by enzyme immunoassay (EIA) and compared with clinical baseline data. RESULTS: Sixty-nine patients were included. The specificity of the anti-CCP antibody test for RA was 96%, and the sensitivity was 44%. There was a significant difference between the four diagnosis groups in the anti-CCP antibody test, probability (p)<0.001, whereas no significant differences were found concerning COMP. The baseline serum COMP test correlated with age (p=0.0001), joint score for swollen joints (p=0.02), and C-reactive protein (CRP) (p=0.02). CONCLUSION: This study confirms the high diagnostic specificity of anti-CCP antibodies for rheumatoid arthritis (RA) in a prospective population-based study of very early arthritis. Raised serum COMP levels were common in all diagnosis groups in this series, indicating cartilage involvement in both self-limiting and non-erosive disease.

Adult↗

A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis.

OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.

Adult↗

Cytokine and chemokine receptor profile of peripheral blood mononuclear cells during treatment with infliximab in patients with active rheumatoid arthritis.

OBJECTIVES: To analyse immunological changes during treatment with a monoclonal anti-tumour necrosis factor alpha (TNFalpha) antibody, infliximab, in patients with rheumatoid arthritis (RA). METHODS: 25 patients with RA and 5 patients with other arthritides were studied during the first 6 weeks of treatment with infliximab. At the start of treatment and after 2 and 6 weeks, spontaneous expression of CCR3 and CCR5 on peripheral blood T cells and monocytes was studied by flow cytometry. The secretion and mRNA expression of interferon gamma (IFNgamma), interleukin (IL)4, IL5, and TNFalpha from phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells was measured with an ELISA and RT-PCR. Plasma levels of C reactive protein, serum amyloid protein A, rheumatoid factor, and antibodies to filaggrin and citrullinated cyclic peptide were measured with an ELISA. RESULTS: The number of CD4 T cells and CD14 monocytes expressing CCR3 (p = 0.013, p = 0.009, respectively) and CD8 T cells expressing CCR5 (p = 0.040) as well as PHA stimulated secretion of IL4 and IFNgamma (p<0.05) increased during treatment in patients with RA. 15 (60%) patients with RA achieved clinical response (at least ACR20) during the first 2 weeks. The number of T cells expressing CCR3 and CCR5 was higher before treatment in non-responders than in responders (p<0.05). The number of T cells increased in responders. CONCLUSION: Increase in secretion of Th1 and Th2 cytokines together with induced expression of chemokine receptors on T cells and monocytes suggest restoration of peripheral cell mediated immunity and blockade of the accumulation of inflammatory cells in joints as response to treatment.

Adult↗

Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study.

OBJECTIVE: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA). METHODS: 186 patients from 12 countries were enrolled in a randomised, double blind, placebo controlled trial. Inclusion criteria were inflammatory arthritis of < or =6 swollen joints, and disease duration of < or =2 months. All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo. Clinical assessments were made at 4 week intervals for 24 weeks. RESULTS: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days. Mean C reactive protein (CRP) was 48 mg/l, and approximately 50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics. There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention to treat basis or according to protocol completion. The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different. Adverse events were generally mild, but were more commonly reported in the azithromycin group. CONCLUSIONS: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA.

Adolescent↗

Immune activation in the small intestine in patients with rheumatoid arthritis.

OBJECTIVES: To determine whether inflammation in the gut associated immune system is activated in rheumatoid arthritis (RA). The expression of chemokine receptor- (CCR4, CCR5) and cytokine- (interleukin (IL)2, IL10, interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha), and transforming growth factor beta (TGFbeta)) specific mRNA in intestinal biopsy samples from patients with RA was examined. METHODS: Duodenal biopsy samples from 13 patients with RA and 15 control subjects were studied. The mRNA expression of CCR4, CCR5, IL2, IL10, IFNgamma, TNFalpha, and TGFbeta in intestinal biopsy samples was demonstrated by real time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The mRNA expression of CCR4, CCR5, and IL10 in intestinal biopsy samples was increased in patients with RA in comparison with control subjects (p = 0.001, p = 0.046, p = 0.019). No difference in the expression levels of IL2, IFNgamma, TNFalpha, or TGFbeta was seen between patients with RA and controls. CONCLUSIONS: The increased intestinal mRNA expression of IL10, CCR5, and CCR4 suggests that gut associated immune cells are activated in patients with RA.

Adult↗

Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: evidence for different locus-specific effects in polyarticular vs pauciarticular subsets and a shared DRB1 epitope.

This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P<10(-6) for both methods) that is flanked by DQB1 and DRB1. Analysis of the DRB1 locus suggested that DRB1*0801 and DRB1*1101 rather than DQA1 or other HLA alleles may be responsible for conferring susceptibility to disease. These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIA DRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule. Most importantly, in pauciarticular patients, the strong association does not extend to proximal markers as it does in polyarticular patients (P<0.00001). Analysis strongly suggests that the difference is because of additional JIA susceptibility loci within the MHC being present in polyarticular RF negative patients.

Age of Onset↗

The costs of early inflammatory joint disease: a population-based study in southern Sweden.

OBJECTIVE: To study the costs and use of healthcare for patients during the first months with early joint inflammation, in a population-based prospective referral study in Southern Sweden. METHODS: Adult patients with arthritis for < 3 months and with onset of symptoms between 1 May 1999 and 1 May 2000 were referred from primary health centres to rheumatologists. Four clinical assessments were performed during a 6-month follow-up period. The direct medical costs for inpatient stays, outpatient visits, visits to general practitioners, and visits to health professionals, as well as costs for medication, radiographs, and laboratory tests were recorded from the onset of the disease up to 6 months of follow-up. Indirect costs for sick leave were also recorded. RESULTS: Fifty-six of 71 referred patients agreed to participate. Thirteen (23%) had RA, 21 (38%) had reactive arthritis (ReA), 14 (25%) had undifferentiated arthritis, and eight (14%) had other arthritides. The median cost per patient in the entire group was USD 3362. The median cost per patient in the RA group was USD 4385, and USD 4085 in the ReA group. There was no statistically significant difference in the median costs per patient in the different diagnostic groups. Sick leave accounted for 44% of the total costs in the entire group, and 46% and 47%, respectively, in the RA and ReA groups. CONCLUSION: The costs of early arthritis are already considerable during the first months of the disease following the onset of the symptoms. The indirect costs due to sick leave accounted for nearly half of the costs.

Arthritis, Reactive↗

Evaluation of the arthritis impact measurement scales (AIMS2) in Finnish patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the validity and reliability of the Finnish version of the Arthritis Impact Measurement Scales (AIMS2) in Finnish patients with rheumatoid arthritis (RA). METHODS: The reliability of the Finnish AIMS2 (Finn-AIMS2) questionnaire was assessed by test retest procedure and internal consistency of health-status scales. Construct validity was assessed by factor analysis, and convergent validity by correlation coefficients, with several disease activity and functional status variables. RESULTS: Internal consistency was 0.79-0.89 and test retest reliability 0.72-0.97. Factor analysis identified three factors: physical, psychosocial, and pain. There were strong correlations between the Finn-AIMS2 health-status scales and the Health Assessment Questionnaire (HAQ). CONCLUSION: The Finn-AIMS2 questionnaire is a reliable and valid instrument for measuring health status in middle-aged Finnish patients with RA. The results also support the applicability of AIMS2 in comparisons in multinational studies.

Activities of Daily Living↗

Peptidylarginine deiminase, the arginine to citrulline converting enzyme, is frequently recognized by sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: Antibodies to citrulline-containing epitopes of filaggrin are highly specific for rheumatoid arthritis (RA). We studied whether the enzyme peptidylarginine deiminase (PAD), responsible for the post-translational modification of peptide-bound arginine residues to citrulline, constitutes an antigen for patients with RA. METHODS: IgG antibodies to PAD were measured by enzyme-linked immunosorbent assay (ELISA) in sera from patients with RA, systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), multiple sclerosis (MS) and healthy controls. RESULTS: Compared to healthy controls, raised levels of IgG antibodies to PAD were found in 50 of 57 recent-onset RA patients (88%) and in 40 (70%) of the same 57 patients 3 years later (p<0.0001 for both comparisons). Eleven of 51 (22%) patients with RA of long duration, 19/43 (44%) patients with SLE and 16/19 (84%) patients with pSS, but none of 20 patients with MS, had elevated anti-PAD levels. CONCLUSION: The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.

Adult↗

Increased inflammatory activity parallels increased basal nitric oxide production and blunted response to nitric oxide in vivo in rheumatoid arthritis.

BACKGROUND: Endothelial dysfunction, defined as loss of bioactivity of NO in the vessel wall, is thought to precede atherosclerosis. OBJECTIVE: To determine whether endothelial dysfunction characterises patients with RA and whether these patients have increased inducible nitric oxide synthase (iNOS) dependent NO production in vivo. METHODS: and results: Twenty patients with RA and 33 normal subjects received intrabrachial artery infusions of endothelium dependent (acetylcholine (ACh)) and independent (sodium nitroprusside (SNP)) vasodilators to determine arterial responsiveness to NO. Basal flow and its percentage decrease by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of both iNOS and endothelium dependent NOS (eNOS), was used to determine the contribution of iNOS and eNOS dependent NO to basal flow. Both SNP (p<0.01) and ACh (p<0.05) increased blood flow significantly less in patients with RA than normal subjects. Serum concentrations of TNFalpha were, within the RA group, inversely correlated with blood flow responses to both SNP (r=-0.67, p=0.002) and ACh (r=-0.64, p<0.005). Basal flow was significantly increased in RA and correlated within this group with serum CRP (r=0.48, p<0.05), TNFalpha (r=0.61, p<0.01) concentrations, and ESR (r=0.68, p<0.002). L-NMMA decreased basal flow significantly more (-34+/-2%) in the patients with RA than the normal subjects (-24+/-3%, p<0.02), suggesting in view of the blunted response to ACh, increased iNOS activity. CONCLUSIONS: Patients with RA have a dual abnormality in NO dependent vascular function. Basal blood flow is increased in proportion to inflammatory activity and more inhibited by L-NMMA, suggesting increased iNOS activity, and responsiveness to NO is reduced.

Acetylcholine↗

Antibiotic treatment and long term prognosis of reactive arthritis.

OBJECTIVE: To evaluate whether a three month course of lymecycline has an effect on the long term prognosis of reactive arthritis (ReA). METHODS: In 1987-88 a double-blind controlled study with three month course of lymecycline/placebo was conducted. 17 of 23 patients treated at the outpatient department of Helsinki University Central Hospital volunteered to take part in a follow up study, where a physical examination were performed, and erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and radiographs of the lumbosacral spine and sacroiliac joints and of symptomatic peripheral joints were examined. RESULTS: 16/17 (94%) patients reported some kind of back pain and 10/17 (59%) peripheral joint symptoms during the follow up. Two patients had unilateral grade 1 sacroiliitis, one patient grade 4 sacroiliitis, and one patient bilateral grade 2 sacroiliitis. In one patient the disease had progressed to ankylosing spondylitis (AS), and in another to chronic spondyloarthropathy. In addition, two patients had small erosions in radiocarpal joints. No statistically significant differences were found between placebo and lymecycline groups in the development of chronic arthritis, sacroiliitis, or AS. CONCLUSION: The results of the initial study showed that long term treatment with lymecycline in patients with acute ReA decreased the duration of arthritis in those with Chlamydia trachomatis triggered ReA, but not in other patients with ReA. Ten years after the acute arthritis one patient had developed AS, and three had radiological sacroiliitis, three patients had radiological changes at peripheral joints. Long term lymecycline treatment did not change the natural history of the disease.

Adult↗

Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection.

OBJECTIVE: To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection. METHODS: From 15 October to 6 November 1998, a widespread outbreak of Y pseudotuberculosis serotype O:3 occurred in Finland. A questionnaire on musculoskeletal symptoms was mailed to 38 patients with infection confirmed by culture. All patients who reported joint symptoms were interviewed by phone and their medical records of outpatient visits or hospital admission because of recent joint symptoms were reviewed. RESULTS: Thirty three of 38 (87%) patients returned the questionnaire. Reactive musculoskeletal symptoms were reported by 5/33 (15%): four patients (12%) fulfilled the criteria for ReA and one additional patient had reactive enthesopathy. The patients with ReA were adults (age range 40-47 years), whereas the patient with reactive enthesopathy was a 14 year old boy. In all patients with ReA, the arthritis was polyarticular. In addition to peripheral arthritis, other musculoskeletal symptoms included sacroiliitis (one patient), pain in Achilles tendon (one patient), and heel pain (two patients). HLA-B27 was positive in all the three patients tested. In three of four patients with ReA, the duration of acute arthritis was over six months. CONCLUSION: Y pseudotuberculosis serotype O:3 infection is frequently associated with ReA and the clinical picture is severe.

Adolescent↗

Campylobacter-triggered reactive arthritis: a population-based study.

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.

Adult↗

Mortality in patients with rheumatoid arthritis treated actively from the time of diagnosis.

OBJECTIVES: To evaluate the mortality rates among patients with early rheumatoid arthritis (RA) treated actively according to the "sawtooth" strategy. METHODS: The study included 150 early, disease modifying antirheumatic drug (DMARD) naive patients with RA from two patient cohorts. The first cohort was assembled between 1986 and 1989 (87 patients, aged 19-65 years at onset) and the second between 1991 and 1993 (63 patients, aged 27-83 years at onset). The mean duration of symptoms at the time of diagnosis was 7.1 months (range 2-24). The clinical data and the use of DMARDs were systematically recorded. The causes of death were obtained from death certificates and medical records, if available. The data were collected up to 1 November 2000. RESULTS: During a follow up time of 7-14 years, 24 patients died. The standardised mortality ratio was not increased (0.93 in the first cohort and 1.62 in the second cohort). Age adjusted mortality rates did not differ statistically significantly between the two patient cohorts. The causes of death included malignancy (8 patients); cardiovascular diseases (10); respiratory disease (4), including two patients with pneumonia; sepsis (one); and RA (one). High inflammatory activity, disease activity, and poor functional ability at study entry, and the presence of extra-articular features during the follow up were more common among the patients who had died. CONCLUSIONS: No statistically significant increase in mortality rates was seen in these actively treated early RA cohorts during the follow up. High disease activity at the onset and the development of extra-articular features seem to be associated with mortality.

Adult↗