Diagnosing ANCA-associated vasculitis in ANCA positive patients: A retrospective analysis on the role of clinical symptoms and the ANCA titre.

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered.

Tumour necrosis factor blocking agents and progression of subclinical atherosclerosis in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is associated with an increased cardiovascular risk that might be due to the chronic underlying inflammatory process. We investigated whether subclinical atherosclerosis of the carotid artery in patients with AS was reduced after anti-inflammatory treatment with tumour necrosis factor (TNF) inhibitors in a prospective observational cohort study. METHODS: 67 out of 81 AS patients who used TNF inhibitors and underwent ultrasonography at baseline returned for follow-up after 4.9 years. Of all patients, 12 (15%) discontinued the use of TNF inhibitors. Assessments of medication use, AS-related factors and cardiovascular risk factors were measured at baseline and repeated at follow-up. B-mode carotid ultrasonography was used to investigate arterial wall parameters, including carotid intima-media thickness (cIMT) and Young's elastic modulus (YEM). RESULTS: After a median 4.9 years of follow-up, cIMT did not change significantly (paired t test +0.011 mm, p=0.561) in those who continued the use of TNF inhibitors, while cIMT increased substantially (+0.057 mm, p=0.069) in those who did not continue their use of TNF inhibitors. The effect of TNF inhibitors was mainly mediated by a subsequent decrease in AS disease activity. Vascular elasticity (as measured with YEM) did not change significantly in patients who discontinued TNF inhibitors or those who continued TNF inhibitors. CONCLUSIONS: The use of TNF inhibitors might stabilise or slow down the progression of subclinical atherosclerosis in AS patients, reflecting a decreased cardiovascular risk in these patients.

Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial.

OBJECTIVE: To compare the effects of aggressive tight control therapy and conventional care on radiographic progression and disease activity in patients with early mild inflammatory arthritis. METHODS: Patients with two to five swollen joints, Sharp-van der Heijde radiographic score (SHS) <5 and symptom duration ≤2 years were randomized between two strategies. Patients with a definite non-RA diagnosis were excluded. The protocol of the aggressive group aimed for remission (DAS < 1.6), with consecutive treatment steps: MTX, addition of adalimumab and combination therapy. The conventional care group followed a strategy with traditional DMARDs (no prednisone or biologics) without DAS-based guideline. Outcome measures after 2 years were SHS (primary), remission rate and HAQ score (secondary). RESULTS: Eighty-two patients participated (60% ACPA positive). In the aggressive group (n = 42), 19 patients were treated with adalimumab. In the conventional care group (n = 40), 24 patients started with hydroxychloroquin (HCQ), 2 with sulfasalazine (SSZ) and 14 with MTX. After 2 years, the median SHS increase was 0 [interquartile range (IQR) 0-1.1] and 0.5 (IQR 0-2.5), remission rates were 66 and 49% and HAQ decreased with a mean of -0.09 (0.50) and -0.25 (0.59) in the aggressive and conventional care group, respectively. All comparisons were non-significant. CONCLUSION: In patients with early arthritis of two to five joints, both aggressive tight-control therapy including adalimumab and conventional therapy resulted in remission rates around 50%, low radiographic damage and excellent functional status after 2 years. However, full disease control including radiographic arrest in all patients remains an elusive target even in moderately active early arthritis. Trial registration. Dutch Trial Register, http://www.trialregister.nl/, NTR 144.

Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low systemic inflammatory activity.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457-961%) vs 797% (95% CI, 556-1,037%), P = 0.59 and 37% (95% CI, 26-47%) vs 41% (95% CI, 31-50%), P=0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease.

Signs of accelerated preclinical atherosclerosis in patients with ankylosing spondylitis.

OBJECTIVE: Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk. We investigated subclinical atherosclerosis and arterial stiffness in patients with AS compared with controls, and identified CV and AS related risk factors for atherosclerotic disease. METHODS: A total of 59 patients with AS who were scheduled for etanercept treatment according to the ASsessments in Ankylosing Spondylitis guidelines and 30 healthy controls were recruited. Subclinical atherosclerosis was assessed as the average intima-media thickness (IMT) of the common carotid artery. Arterial stiffness was determined by distensibility, compliance, and Young's elastic modulus of the carotid artery. RESULTS: AS patients had a greater IMT (0.62 +/- 0.09 mm vs 0.57 +/- 0.09 mm in controls; p = 0.02), a difference that remained after adjustment for traditional CV risk factors. AS was associated with higher carotid pulse pressure (47 +/- 7 mm Hg vs 44 +/- 8 mm Hg in controls; p = 0.04), but this was not due to local vessel wall properties. Among AS patients, age and body mass index (BMI) were determinants of IMT. Age, BMI, total cholesterol, triglycerides, and disease duration were identified as determinants of stiffness indices. No relationship was found between large-vessel properties and higher Bath AS disease indices or C-reactive protein values. CONCLUSION: AS was associated with subclinical atherosclerosis and arterial stiffness, supporting epidemiological evidence of an increased CV risk in these patients. Whether these differences are due to AS or to a higher prevalence of CV risk factors in patients with AS remains to be determined.

Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis.

OBJECTIVE: To study the usefulness of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum amyloid A (SAA) for response prediction and monitoring of anti-tumor necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients. METHODS: Patients were included consecutively before starting etanercept or infliximab treatment. ASsessment in Ankylosing Spondylitis (ASAS) response, defined as a 50% improvement or an absolute improvement of 2 points of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 0-10 scale), was assessed at 3 months. Inflammatory markers and the BASDAI were collected at baseline and 1 and 3 months. Longitudinal data analysis was performed to compare associations between inflammatory markers and the BASDAI over time by calculating standardized betas. Predictive values of baseline levels of inflammatory markers for ASAS response were calculated. RESULTS: In total, 155 patients were included, of whom, after 3 months of treatment, 70% in the etanercept cohort and 71% in the infliximab cohort responded. All markers, notably SAA, decreased significantly (P < 0.0001). Standardized betas were 0.49 for ESR, 0.43 for CRP, and 0.39 for SAA. Normal baseline levels of CRP and SAA were significantly associated with nonresponse. A combination of elevated CRP and SAA levels at baseline revealed the highest predictive value (81%) for ASAS response. CONCLUSION: ESR, CRP, and SAA were significantly associated with the BASDAI over 3 months, and the association with ESR was the strongest. Elevated baseline CRP and SAA levels revealed the highest predictive value for response. Together, this study demonstrates that inflammatory markers, and notably CRP and SAA, may facilitate patient selection and monitoring of efficacy of anti-TNF treatment in AS, and could be added to response criteria.