Generalized bone loss in early rheumatoid arthritis patients followed for ten years in the biologic treatment era.

BACKGROUND: Osteoporosis is a well-known extra articular manifestation in rheumatoid arthritis (RA). Biologic disease modifying anti rheumatic drugs (DMARDs) has been shown to be superior to synthetic DMARDs to reduce bone destruction including generalized bone loss in RA. Our aim was to study short- and long term changes in hip and spine bone mineral density (BMD) in early RA patients treated during the first decade with available biologic DMARDs. METHODS: RA patients diagnosed at an out-patient clinic between 1999 and 2001 were consecutively enrolled. Demographic, disease and treatment data were collected and BMD was assessed by dual energy X-ray absorptiometry at baseline and after 2, 5 and 10 years. RESULTS: The 92 included RA patients had a baseline mean age (SD) of 50.9 (13.3) years and symptom duration of 12.4 (6.7) months, 62.0% were women and 66.3% were RF positive. In the first 2 years ever use of biologic DMARDs was 18.5%, synthetic DMARDs 91.3% and prednisolone 62.0% whereas the figures for the subsequent 8 years were 62.6%, 89.2% and 51.4%, respectively. The annual rate of BMD loss in the first 2 years and the subsequent 8 years was at femoral neck -1.00% vs. -0.56%, at total hip -0.96% vs. -0.41% and at spine L1-4 -0.42% vs. 0.00%. CONCLUSIONS: Our study adds evidence that aggressive anti-inflammatory treatment including biologic DMARDs reduces the rate of bone loss in RA. Indicating that the burden of osteoporosis is reduced in RA patients treated in clinical practice in the new millennium.

Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand.

OBJECTIVE: Elevated levels of IL-17A have been detected in the inflamed synovium of RA patients, and murine arthritis models deficient in IL17A have shown reduced inflammation. Our aim was to investigate IL17A as a candidate gene for RA, and to assess correlations between risk variants and disease phenotypes. METHODS: Five single nucleotide polymorphisms (SNPs) were selected to tag the genetic variability of the IL17A region and were genotyped by TaqMan technology on 950 RA cases and 933 random controls from Norway. Associations to progression of radiographic damage and presence of autoantibodies were examined in a 10-yr follow-up cohort of early RA. In addition, 580 RA patients and 504 controls from New Zealand were used as a replication data set. RESULTS: A weak association between RA and the promoter SNP rs2275913 [odds ratio (OR) = 1.17; 95% CI 1.02, 1.34; P = 0.02] was found in the Norwegian population. The association was also evident at the genotype level where it indicated a recessive model. The allelic association was not replicated in the RA cohort from New Zealand (OR = 0.96; 95% CI 0.81, 1.16; P = 0.69). However, combined analysis suggested a weak recessive association (OR = 1.19; 95% CI 1.02, 1.37; P = 0.02). No significant associations were observed with radiographic progression, anti-cyclic citrullinated peptide or IgM-RF. CONCLUSIONS: Modest evidence of an association with IL17A in Norwegian RA patients was observed. Although, our findings were not replicated in an independent RA material from New Zealand, a significant common risk estimate indicated that IL17A warrants further investigation in RA.

Clinical and Radiographic Outcomes in Patients Diagnosed with Early Rheumatoid Arthritis in the First Years of the Biologic Treatment Era: A 10-year Prospective Observational Study.

OBJECTIVE: To study short-term and longterm clinical and radiographic outcomes in patients with early rheumatoid arthritis (RA) in the first decade of the biologic treatment era. METHODS: Patients with early RA diagnosed at a rheumatology outpatient clinic were consecutively enrolled between 1999 and 2001. Data were collected on demographic characteristics, disease activity, patient-reported outcomes, and treatments. Radiographs of hands and feet were performed at baseline and after 2, 5, and 10 years and scored according to the Sharp/van der Heijde method, yielding a modified total Sharp score (mTSS). RESULTS: Mean baseline age for the 94 included patients (36 men and 58 women) was 50.4 years and symptom duration 12.3 months; 67.8% were rheumatoid factor-positive. The proportion of patients in remission and in low, moderate, and high disease activity status was at baseline 4.3%, 1.1%, 35.1%, and 59.6% and at 10 years 52.1%, 20.5%, 27.4%, and 0.0%, respectively. For the period 0-2 years, 62.8% had used prednisolone, 91.5% synthetic disease-modifying antirheumatic drug (DMARD), and 18.1% biologic DMARD, and for the period 2-10 years the numbers were 50.6%, 89.3%, and 62.7%, respectively. At baseline, 70% of the patients had erosions on radiographs. Mean annual change in mTSS was for 0-2 years 3.4, 2-5 years 1.7, and 5-10 years 1.2. CONCLUSION: A large proportion of our patients with RA diagnosed and treated in the new biologic treatment era achieved a status of clinical remission or low disease activity and had only a minor increase in radiographic joint damage after the first years of followup.

The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis.

INTRODUCTION: We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF. METHODS: Patients with UA (exclusion of definite non-rheumatoid arthritis (RA) diagnoses) included in the Norwegian very early arthritis clinic were assessed for development of persistent arthritic disease. The effect of antibody level on the likelihood of persistent arthritis was investigated, and the sensitivity and specificity for persistent arthritis for anti-CCP and IgM RF, separately and combined, was determined. RESULTS: A total of 376 UA patients were included (median arthritis duration 32 days). 59 (15.7%) patients were IgM RF positive, and 62 (16.5%) anti-CCP positive. One hundred, seventy-four (46.3%) had persistent disease after one year. Overlap of anti-CCP and IgM RF positivity was 58%. Sensitivity/specificity for persistent arthritis was 28/95% for IgM RF alone, 30/95% for anti-CCP alone, and 37/92% for positivity of both anti-CCP and IgM RF. The likelihood for persistent disease increased with increasing levels of both anti-CCP and IgM RF. CONCLUSIONS: The likelihood of developing persistent arthritis in UA patients increases with the level of anti-CCP and IgM RF. Testing both anti-CCP and IgM RF has added predictive value in UA patients. This study suggests that antibody level should be taken into account when making risk assessments in patients with UA.

Pattern of joint involvement and other disease characteristics in 634 patients with arthritis of less than 16 weeks' duration.

OBJECTIVE: To investigate the distribution of joint involvement in a cohort of patients with very recent onset arthritis and describe the disease characteristics in these patients. METHODS: A very early arthritis clinic (NOR-VEAC) was established as a multicenter study. General practitioners were asked to refer patients presenting with at least 1 swollen joint of maximum 16 weeks' duration. Clinical and laboratory markers were examined. RESULTS: We included 634 patients during the first 3 years, with mean (25th-75th percentile) arthritis duration of 30 (11-63) days. Monoarthritis was present in 243 (38.3%) patients, 216 (34.1%) had oligoarthritis, and 175 (27.6%) polyarthritis. Patients with polyarthritis were older, had longer duration of arthritis, and were more frequently anti-cyclic citrullinated peptide antibody and rheumatoid factor-positive. Patients in all 3 joint pattern groups (mono-/oligo-/polyarthritis) reported substantial effect on physical function, pain, and fatigue and had elevated levels of acute-phase reactants. Knee or ankle arthritis was most frequent in patients with mono- and oligoarthritis, whereas small joint involvement was most frequent in patients with polyarthritis. CONCLUSION: Patients with recent-onset arthritis report a substantial influence on health status. Mono- and oligoarthritis are at least as frequent as polyarthritis. Polyarthritic patients more frequently exhibit features associated with a worse outcome.

Positive anti-citrullinated protein antibody status and small joint arthritis are consistent predictors of chronic disease in patients with very early arthritis: results from the NOR-VEAC cohort.

INTRODUCTION: The current 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) have proven less useful in early arthritis. The objective of this study was to identify and compare predictors of three relevant outcomes of chronic arthritis in a cohort of very early arthritis patients. METHODS: The Norwegian Very Early Arthritis Cohort (NOR-VEAC) includes adult patients with at least one swollen joint of < or = 16 weeks' duration. Patients are followed for 2 years with comprehensive clinical and laboratory examinations. Logistic regression analyses were performed to determine independent predictors of three outcomes: persistent synovitis, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and established clinical RA diagnosis within one year. RESULTS: Of 384 patients eligible for one year follow-up (56.3% females, mean (SD) age 45.8 (14.7) years, median (IQR) duration of arthritis 31 (10-62) days), 14.4% were anti-CCP2 positive, and 11.2% were IgM RF positive. 98 patients (25.5%) had persistent synovitis, 106 (27.6%) had received DMARD treatment during follow-up, while 68 (17.7%) were diagnosed with RA. Consistent independent predictors across all three outcomes were positive anti-citrullinated protein antibody (ACPA) status (odds ratio (OR) 3.2, 5.6 and 19.3), respectively, and small joint arthritis (proximal interphalangeal joint (PIP), metacarpo-phalangeal joint (MCP), and/or metatarso-phalangeal joint (MTP) joint swelling) (OR 1.9, 3.5, and 3.5, respectively). CONCLUSIONS: Positive ACPA status and small joint arthritis were consistent predictors of three relevant outcomes of chronic arthritis in very early arthritis patients. This consistency supports DMARD prescription as a valid surrogate endpoint for chronic arthritis. Importantly, this surrogate is used in ongoing efforts to develop new diagnostic criteria for early RA.