Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor α that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose ...responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug.
To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period.
94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1-≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years).
ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853-82 437) vs median 2454 AU/ml, IQR 449-7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011).
In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.
To explore the sensitivity to change of colour Doppler ultrasound (CDUS) in giant cell arteritis (GCA).
This was a blind, prospective study composed of 30 consecutive patients diagnosed with GCA. In ...25 of the cases this was their first episode of GCA, and 13 of the cases were relapses. All participants had presented with at least 1 branch involvement in the basal sonography, and steroid treatment had been initiated. A CDUS was performed every 2 weeks during the first month, and every 4 weeks thereafter, until halo disappearance was observed in the bilateral parietal and frontal branches of the temporal superficial artery.
Thirty-eight episodes of GCA in 30 different patients (19 women and 11 men; mean age, 79.24±4.76 years; range 70-88) were followed. Dark halo disappearance occurred in 95% of cases. The mean time until halo disappearance was observed was around 11 weeks, with 50% of cases showing halo disappearance within the first 8 weeks. The relapse cases appeared to have less arterial wall affectation than the primary GCA cases, reduced erythrocyte sedimentation rate ESR and an earlier loss of the halo sign. Patients with a smaller number of affected branches required less time for halo disappearance.
CDUS shows a sensitività to change in GCA. Halo disappearance is rare before two weeks, and it frequently persists during the first two months after initiating steroid therapy. Our data emphasise the advantages of using CDUS to monitor GCA activity.
BACKGROUNDCandidiasis is the most frequent mycotic infection of the oral cavity. The aim of this study was to investigate the presence of clinical oral candidiasis and Candida albicans yeast in a ...population diagnosed of primary Sjögren's syndrome (pSS) and to study the possible factors associated with this infection. MATERIAL AND METHODSAn observational cross-sectional study was conducted in 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) where patient based information (demographic and medical, tobacco and alcohol consumption history), intraoral parameters (presence of dentures, clinical signs of candidiasis), salivary analytical information (number of Candida albicans as colony-forming units per millilitre (CFU/mL), salivary pH levels, unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. RESULTS13.1% of pSS patients presented oral signs of candidiasis. Denture stomatitis and angular cheilitis were the most common lesions. 87.5% of patients with clinical candidiasis presented reduced pH levels and salivary flow in both UWS and SWS. A significant statistical negative correlation was found between CFU/mL of Candida albicans and levels of UWS and SWS. A negative correlation was found between pH levels and CFU/mL, although not statistically significant. CONCLUSIONSA reduced salivary flow may predispose pSS patients to Candida albicans overgrowth, which may show with clinical signs. Preventive measures are of great importance to avoid and to treat this condition promptly.
We undertook this study to evaluate the responsiveness of Doppler ultrasound (US) to urate lowering therapy (ULT) in gout patients.
Twenty-four consecutive patients were prospectively included from ...an outpatient clinic. The patients underwent clinical, and US assessment at baseline and after 6, 12 and 24 months of ULT. The US assessment was made by another rheumatologist blinded to the clinical data. Standardised examinations were performed in four joints (both first metatarso-phalangeals and knees) and the patellar tendons. The Doppler signals were scored. The mean and standard deviation were calculated for each parameter. The comparison between the quantitative values was performed by Student's t-test. Sensitivity to change in the US examinations was assessed by estimating the smallest detectable difference (SDD) in the total Doppler score.
A Doppler signal was detected in 95.8% of the patients at the baseline. A significant parallel improvement in the serum urate level, clinical parameters and in Doppler scores was found at the follow-up assessment. 62% of the patients had achieved a uric concentration level below 6 mg/dl at one year. At two years, persistence of a Doppler signal was found in 72.7% of the patients. The SDD in the Doppler score at 2 years was 1.92, lower than the difference achieved.
The Doppler US findings show significant improvement and responsiveness after ULT in gout patients. The Doppler signal persistence after two years of treatment is marked. This finding introduces a reflection on the accuracy of the current outcome measures and treatments.
The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi ...transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients.
Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells.
As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months relative risk 2.91 (95% CI 1.37, 6.47). A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone.
An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.
The aim of this study was to evaluate the construct validity of enthesis US in the assessment of disease activity in SpA.
A longitudinal Achilles enthesis US study in patients with early SpA was ...undertaken. Achilles US examinations were performed at baseline, 6 and 12 months and compared with clinical outcome measures collected at the baseline visit.
Bilateral Achilles enthesis of 146 early SpA patients (68 women) were analysed. Basal mean BASFI, BASRI-spine, BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) were 2.44 (s.d. 2.05, range 0-8), 0.67 (s.d. 0.74, range 0-3), 4.60 (s.d. 2.07, range 0-9.5) and 2.51 (s.d. 1.16, range 0-5), respectively. The mean ESR was 15.0 mm/h (s.d. 16.99, range 0-109) and the mean CRP was 8.67 mg/l (s.d. 16.98, range 1-90). At baseline, the Achilles Doppler signal and US structure alteration were significantly associated with higher CRP and ESR levels. Patients who had very high disease activity at baseline, as assessed by the ASDAS (>3.5), had a significantly higher Achilles total US score at baseline (P = 0.04), and ASDAS <1.3 predicted no Doppler signal at 6 and 12 months. Overall, the Achilles total US score was significantly higher in patients with higher levels of CRP (baseline P = 0.04, 6 months P = 0.006, 12 months P = 0.03) and ESR (baseline P = 0.02, 6 months P = 0.04, 12 months P = 0.005) at baseline. The Doppler signal at the baseline visit predicted a higher total US score at 6 and 12 months.
Doppler US has significant associations with other commonly accepted disease activity measures, such as ESR, CRP and ASDAS, and seems to be an objective outcome measure for enthesitis.
The goal of this study was to investigate the usefulness of a short ultrasound (US) assessment in gout.
Patients with gout, confirmed by urate crystal identification, and having at least one ...symptomatic flare in the last three months were included. Standardised US examinations of sixteen joints and eight tendons in the lower limbs were carried out. Six lesions were studied: hyperechoic spots in the synovial fluid, hyperechoic cloudy areas (HCA), bright stippled aggregates (BSA), the double contour sign (DCS), erosions and the Doppler signal. For reliability, inter-reader analyses were performed by five rheumatologists. With the results, a short US assessment was created.
Twenty-nine consecutive patients were included (93% men). The Doppler signal, HCAs and BSAs appeared in 100%, 97% and 93% of the patients, respectively. The DCS was found in 69% of patients. The locations that were most affected were the first metatarsophalangeal joint (MTP) and the knee joints, both of which are in 93% of patients. Reliability analyses showed consistent results for erosions, the Doppler signal, HCAs and the DCS in the 1st MTP (k=0.818, k=0.958, k=0.739 and k= 0.697, respectively) and for the DCS in the knees (k=0.779). A six-minute US examination of four joints (knees and the 1st MTPs) detected HCAs or DCS in 97% of cases.
A US examination of four joints for two elemental lesions (the DCS and HCAs) is feasible, reliable and has face and content validity as a diagnostic test in patients with crystal-proven gout.
To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).
This is a ...cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.
888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.
Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.
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