Search

To investigate the performance and factors of influence of optical spectral transmission (OST) imaging as a new technique for measuring joint inflammation in rheumatoid arthritis (RA). OST was performed in 24 RA patients and 37 controls. Mann–Whitney U-test was used to assess differences in OST score between RA patients and controls. Receiver operating characteristics (ROC), linear regression and generalized estimating equations analysis were used to assess the discriminative capability of OST and the association of OST score with clinical disease parameters, ultrasound, radiographic features and cardiovascular risk parameters. Median OST score was higher in RA patients than in controls [16.9 (interquartile range 12.77–19.7) vs 12.11 (10.32–14.93)]. At patient level, OST score was moderately associated with ultrasound [beta 0.38 (95% CI 0.16–0.60), p = 0.001] and clinical disease activity [28-joint Disease Activity Score–C-reactive protein beta 0.30 (95% CI 0.04– 0.57), p = 0.024] in RA patients. In controls, male sex, high body mass index, and hypertension were associated with higher OST scores, while these associations were absent in RA. At joint level, the area under the ROC curve for OST score, with ultrasound or clinical swelling as reference, ranged from 0.63 to 0.70. Joint-space narrowing and malalignment were associated with higher OST joint scores, and subchondral sclerosis with lower scores. OST provides an objective measure of synovitis and correlates moderately with other examined disease activity assessment tools. Clinical patient characteristics must be considered when interpreting the results. [ABSTRACT FROM AUTHOR]

SC Heslinga,1,2 TC Konings,3 IE van der Horst-Bruinsma,1,2 O Kamp,3 VP van Halm,3,4 HACM de Bruin-Bon,4 MJ Peters,5 MT Nurmohamed1,2 1Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands; 2Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands; 4Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; 5Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Background: Diastolic left ventricular (LV) dysfunction appears more prevalent in ankylosing spondylitis (AS). The effects of tumor necrosis factor alpha (TNF-α) blocking therapy, a strong and effective anti-inflammatory drug, on diastolic LV function in AS are unknown. The objective of the study was to find the effects of 1-year treatment with golimumab 50 mg subcutaneously once per month on systolic and diastolic LV dysfunction in AS patients.Methods: Forty consecutive AS patients were treated with TNF-α blocking therapy for 1 year. Transthoracic echocardiography was performed in all patients at baseline and after 1 year of treatment.Results: Diastolic LV function improved after treatment in four out of six (67%) AS patients who completed follow-up (P=0.125), and did not develop or worsen in any of the other patients. Treatment with TNF-α blocking therapy had no effect on systolic LV function.Conclusion: These findings give support to the hypothesis that diastolic LV dysfunction improves during treatment with TNF-α blocking therapy. Keywords: ankylosing spondylitis, cardiovascular disease, anti-TNF

To study the long-term effect of 16 weeks of etanercept treatment on disease activity and radiographic changes in patients with suspected non-radiographic axial spondyloarthritis (nr-axSpA). Eighty patients with inflammatory back pain and suspected nr-axSpA, with a Bath Ankylosing Disease Activity Index (BASDAI) ≥ 4, received etanercept (n = 40) 25 mg twice weekly or placebo (n = 40) for 16 weeks. They were followed without treatment restrictions after 24 weeks, for up to 3 years. Comparisons were made between patients who received etanercept or placebo in the first period, and changes in BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), function, and radiographic changes in the spine [according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS)] and sacroiliac joints (Bath Ankylosing Spondylitis Radiology Index (BASRI). After 3 years of follow-up, 84% of the patients were diagnosed with SpA, predominantly axSpA. Biological treatment was started after 24 weeks in 30% of patients. Disease activity scores after 3 years did not reveal significant differences between the initial randomization groups in mean BASDAI scores (mean difference 0.9, 95% CI −1.1;0.7, p = 0.6) and ASDAS (mean ASDAS 0.3, 95% CI 0.6;3.1, p = 0.5). BASMI and function scores remained stable over 3 years. No differences in radiographic changes of the sacroiliac joints or spine were observed over 3 years between the two groups. A short course of etanercept in patients with suspected nr-axSpA did not affect disease activity, the chance of biological treatment, or radiographic progression after 3 years of follow-up. [ABSTRACT FROM AUTHOR]

The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06– 2.65) to 0.46 µg/mL (0.28–0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is characterized by systemic inflammation and the presence of anti-citrullinated protein antibodies (ACPAs), which contain remarkably high levels of Fab glycosylation. Anti-hinge antibodies (AHAs) recognize immunoglobulin G (IgG) hinge neoepitopes exposed following cleavage by inflammation-associated proteases, and are also frequently observed in RA, and at higher levels compared to healthy controls (HCs). Here, we investigated AHA specificity and levels of Fab glycosylation as potential immunological markers for RA. AHA serum levels, specificity, and Fab glycosylation were determined for the IgG1/4-hinge cleaved by matrix metalloproteinase-3, cathepsin G, pepsin, or IdeS, using enzyme-linked immunosorbent assay and lectin affinity chromatography, in patients with early active RA (n = 69) and HCs (n = 97). AHA reactivity was detected for all hinge neoepitopes in both RA patients and HCs. Reactivity against CatG-IgG1-F(ab´)2s and pepsin-IgG4-F(ab´)2s was more prevalent in RA. Moreover, all AHA responses showed increased Fab glycosylation levels in both RA patients and HCs. AHA responses are characterized by elevated levels of Fab glycosylation and highly specific neoepitope recognition, not just in RA patients but also in HCs. These results suggest that extensive Fab glycosylation may develop in response to an inflammatory proteolytic microenvironment, but is not restricted to RA. [ABSTRACT FROM AUTHOR]

To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (β = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). Female AS patients show a lower response to TNFi and a higher disease activity compared to men. [ABSTRACT FROM AUTHOR]

Objectives: Inadequate response to adalimumab can be caused by insufficient blockade of the target tumour necrosis factor (TNF) at low serum concentrations. In such cases, patients may respond to another TNF inhibitor. We investigated whether the serum adalimumab concentration is related to the efficacy of a second TNF inhibitor, etanercept, in rheumatoid arthritis (RA). Methods: Patients with RA starting etanercept treatment were prospectively observed in the Reade Rheumatology Registry. In patients previously on adalimumab, serum concentrations were determined before treatment discontinuation. According to this concentration, three subgroups were formed: < 0.5 μg/mL, 0.5-5.0 μg/mL, and ≥ 5.0 μg/mL. The European League Against Rheumatism (EULAR) good/moderate response rate after 52 weeks of etanercept was compared between the switcher subgroups and biologic-naive patients. Results: In total, 449 consecutive patients were included, of whom 69 switched from adalimumab (15%) and 380 were biologic naive (85%). EULAR good or moderate response was achieved by 74% of the biologic-naive patients and by 72%, 50%, and 52% of switchers with adalimumab concentration < 0.5 μg/mL, 0.5-5.0 μg/mL, and ≥ 5.0 μg/mL, respectively (p = 0.15). Patients with an adalimumab concentration ≥ 0.5 μg/mL were significantly less likely to achieve EULAR good/moderate response on etanercept compared to biologic-naive patients, whereas patients with a concentration < 0.5 μg/mL did not significantly differ from patients starting etanercept without prior biologic treatment. Conclusion: RA patients with an inadequate response to adalimumab, in the presence of sufficient drug concentrations, benefit less from switching to another TNF inhibitor, etanercept. [ABSTRACT FROM AUTHOR]

Objective: To compare rates of drug survival and clinical response during 2 years of follow-up in ankylosing spondylitis (AS) patients treated with etanercept or adalimumab in routine care.Method: Biological-naïve consecutive AS patients treated with etanercept (n = 163) or adalimumab (n = 82) were followed. Treatment discontinuation was due to inefficacy, adverse events, loss to follow-up, planning a pregnancy, or uveitis. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP). Moderate disease activity was defined as an ASDAS-CRP < 2.1.Results: Twenty-seven patients (32.9%) treated with adalimumab and 30 (18.4%) with etanercept discontinued treatment. Cox regression analysis demonstrated a significant difference in survival rate between discontinuation of the drug in adalimumab patients compared with etanercept patients [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.3-4.5, p = 0.005; corrected for confounding factors: HR 2.5, 95% CI 1.3-4.5, p = 0.006]. There was no significant difference at 2 years of follow-up between the adalimumab- and the etanercept-treated patients in mean ± sd ASDAS-CRP (1.9 ± 1.1 and 2.0 ± 0.9, respectively, p = 0.624), and 23 out of 34 (67.6%) compared to 71 out of 117 (60.7%) reached ASDAS-CRP moderate disease activity (odds ratio 0.738, 95% CI 0.329-1.657, p = 0.530).Conclusion: No significant difference was found between AS patients treated with etanercept and those treated with adalimumab in mean ASDAS-CRP and reaching ASDAS-CRP minimal disease activity at 2 year follow-up. Drug survival rate was higher in etanercept- compared to adalimumab-treated patients. However, this should be interpreted cautiously as the risk of allocation bias cannot be excluded. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the pharmacokinetics (PK) and dynamics of tocilizumab (TCZ) in daily practice.Method: An observational study of 66 consecutive RA patients treated with TCZ 8 mg/kg once every 4 weeks intravenously, monitored for 24 weeks. Spearman's rank test was used to investigate the correlation between TCZ concentration and C-reactive protein (CRP). Clinical improvement was assessed at week 24 using the Disease Activity Score in 28 joints (DAS28) compared to baseline, and its relationship with TCZ concentration was investigated using linear regression analyses. TCZ trough concentrations and anti-drug antibodies were measured using an enzyme-linked immunosorbent assay (ELISA) and antigen binding test, respectively.Results: At baseline, 26 patients (39.4%) had a CRP level above 10 mg/L with a median (interquartile range, IQR) of 37.7 (21.9-49.7) mg/L. A TCZ concentration above 1 mg/L was sufficient to normalize CRP levels. Spearman's rank test showed a correlation coefficient of -0.460 (p < 0.0001). The TCZ concentration varied widely, with concentrations < 1 mg/L in 17-31% of patients, depending on the time point of measurement. Anti-TCZ antibodies were detected in one sample. Linear regression analyses showed a coefficient of 0.080 with a 95% confidence interval (CI) of 0.039-0.113 (p < 0.001) for the association between TCZ concentration and ΔDAS28. No confounders were identified.Conclusions: The TCZ standard regimen results in a wide variety of serum TCZ trough concentrations; this is mostly due to target binding and to a lesser extent to immunogenicity. The majority of patients obtained TCZ concentrations > 1 mg/L, which is sufficient for CRP normalization. Therefore, dose taper strategies might be possible in a substantial proportion of patients. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is an anti-inflammatory and potentially antiatherogenic molecule. Some recent reports suggest that tumour necrosis factor alpha (TNFalpha) blockade therapy increases circulating adiponectin levels, but data are sparse and inconsistent.Methods: Data from a double-blind placebo controlled study of onercept in 126 patients with psoriatic arthritis (PsA) and from pre- and post-adalimumab treatment in 171 patients with rheumatoid arthritis (RA) were used to examine the effect of TNFalpha blockade therapy on adiponectin.Results: Despite expected associations of adiponectin with gender and baseline high-density lipoprotein cholesterol and triglyceride, adiponectin levels did not change over time with TNFalpha blockade therapy in either group. The mean+/-SD absolute change in adiponectin levels was -0.23+/-4.6 microg/ml in patients with PsA treated with combined onercept 50 mg and onercept 100 mg (vs placebo, p=0.60) and 0.28+/-3.23 microg/ml in patients with RA treated with adalimumab (vs baseline, p=0.66).Conclusion: These results do not support a significant effect of TNFalpha blockade therapy on circulating adiponectin levels in patients with autoimmune disease. [ABSTRACT FROM AUTHOR]