[Show abstract][Hide abstract] ABSTRACT: Tocilizumab (TCZ) is a humanized monoclonal interleukin-6 (IL-6) receptor antibody which has demonstrated clinical efficacy in the treatment of patients with moderate-severe rheumatoid arthritis (RA) who experienced inadequate response to methotrexate and one or more anti-TNFα agent [1, 2]. The efficacy of TCZ in the treatment of RA is supported by a bulk of evidence which includes randomized clinical trials and observational, ‘field-practice’ studies . TCZ can be administered intravenously at the standard dose of 8 mg/kg either in combination with other disease-modifying antirheumatic drugs (DMARDs) or as a monotherapy . The favorable efficacy and tolerability profile of TCZ is sustained over a long term (up to 9 years) .Although the above-mentioned evidence supports the use of TCZ in clinical practice, additional data are required to fully explore the optimal individualization of this treatment for each single patient .For instance, it has been recently suggested that som ...
Rheumatology International 03/2015; 35(9). DOI:10.1007/s00296-015-3243-z · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over the last decades ultrasound-guided procedures have become increasingly diffused in rheumatology, mainly thanks to the technical advances achieved in the ultrasound (US) field, combined with the greater availability, good portability and reduced cost of US devices, compared to other imaging techniques already used in rheumatology units. The direct visualisation of the tissue under analysis and the real-time imaging performance enabled by US-guidance account for an improved accuracy and directness in needle placement in a number of rheumatology interventions such as tendon and intra-articular injections. Compared with blind procedures, US-guided injections are more accurate and safe and they result in better clinical outcome in terms of joints improvement in function and decreased risk of damages caused by needle misplacement. The accuracy in needle placement of US-guided injections has proven to be important not only in common intra-articular injections, but especially in case of complex anatomical areas like the hip, facet and atlanto-occipital joints, where blinded injections are deemed poorly accurate and thus highly risky. Moreover US guidance can be successfully employed in more complex procedures such as synovial biopsy, portal establishment or arthroscopy, where US can also be combined with other imaging techniques. Overall the employment of US-guided procedures is considered to be safe and well-tolerated, and increases the accuracy and therapeutic effectiveness of the interventions performed. This may pave the way for a more widespread employment of US-guidance in rheumatology units, and new studies could further explore the therapeutic advantages of these procedures.
[Show abstract][Hide abstract] ABSTRACT: Background The role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the response to treatment for rheumatoid arthritis (RA) is not fully understood. Studies investigating changes in the levels of RF in response to synthetic and biological DMARDs have not been able to confirm a definitive relationship between decreased RF subtypes and clinical response, while studies investigating changes in anti-CCP levels have yielded conflicting results.
In addition, to our knowledge the correlation between autoantibodies and tocilizumab treatment has been poorly investigated.
Objectives This study investigates the relationship between the presence and levels of RF and anti-CCP and clinical response to tocilizumab in patients with RA.
Methods This was an observational longitudinal study in 27 patients with active, long-standing RA despite previous treatment with >2 DMARDs and/or steroids. Patients were treated with tocilizumab 8 mg/kg every 4 weeks. All patients were assessed using approved clinical scales (VES, PCR, HAQ, DAS28-VES, DAS28-PCR, CDAI, and SDAI). IgM-, IgA- and IgG-RFs and anti-CCP antibodies were assessed using ELISA at baseline, 3 months (T1), 6 months (T2), and 12 months (T3).
Results All patients showed significant and sustained clinical response to tocilizmuab treatment. All clinical scales with the exception of HAQ significantly decreased. There was a significant correlation (p=0.03) between anti-CCP and SDAI changes from baseline at T1 and T2. Likewise there were no significant correlations between antibody count at T0 and changes in the DAS-28 VES at T1 and at T2. No significant relationship between clinical scales and antibody levels RF-IgG, IgA, IgM and anti-CCP levels were observed.
Conclusions Tocilizumab is effective in treating the clinical symptoms of RA, and the efficacy of this molecule was not correlated with either RF or anti-CCP levels. There is now a growing body of evidence suggesting that markers associated with clinical response may not be the same biomarkers that predict risk of further joint damage
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A880-A880. DOI:10.1136/annrheumdis-2013-eular.2626 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background An association between systemic autoimmune diseases (SADs) and atherosclerosis has been described in many connective tissue diseases, and is known to lead to increased cardiovascular (CV) morbidity and mortality. Systemic sclerosis (SSc) ischaracterised by multi-system organ inflammation, endothelial wall damage and vasculopathy (1). There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (cIMT) and coronary flow reserve (CFR) assessed by means of trans-thoracic echocardiography (TTE).
Objectives The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early CV involvement in a group of SSc patients.
Methods The study involved 20 patients (two males, 18 females; mean age 52.96±12.51 years) with diffuse SSc but no signs or symptoms of CV disease (CVD), and 20 age- and gender-matched controls. All underwent a dipyridamole echocardiographic stress test which included a determination of CFR, and an evaluation of cIMT, arterial stiffness and plasma ADMA levels.
Results All the arterial wall measurements of the diffuse SSc group were significantly different from those of controls and both right and left cIMT, pulse wave velocity (PWV), and stiffness index β were also all significantly elevated in SSc patients compared to healthy controls (Table 1). Moreover, in patients with diffuse SSc CFR was significantly lower (P=0.0033) and plasma ADMA levels higher (P<0.0001) than in healthy controls (Table 1).
Conclusions This study showed that those SSc patients without any clinical evidence of CVD had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):684-684. DOI:10.1136/annrheumdis-2012-eular.797 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The objective of this study was to draw up a set of recommendations for the format and content of the musculoskeletal ultrasonography (MSUS) report in rheumatology.
A panel of rheumatologists, members of the MSUS Study Group of the Italian Society of Rheumatology, met in order to identify the main discrepancies in the MSUS report. A set of 15 recommendations was then defined, aimed at resolving the main discrepancies. They consisted of information about the motivations for the MSUS examination, the equipment, the US modalities and scanning technique, a list of the examined structures and findings, the scoring/grading systems, the number of images and main findings to include and conclusions. Subsequently a Delphi-based procedure was started in order to obtain agreement on a core set of recommendations. Consensus for each recommendation was considered achieved when the percentage of agreement was >75%.
Three complete rounds were performed. The response rate was 85.2% for the first round, 78.3% for the second and 88.9% for the third. Finally, consensus was obtained for 14 of 15 statements. These 14 statements represent the recommendations of the group for the format and content of the report and documentation in MSUS in rheumatology.
To the best of our knowledge, our group has produced the first recommendations for the format and content of the report and documentation in MSUS in rheumatology. The report is an integral part of the MSUS examination and its use in a homogeneous form can help in the correct interpretation of the findings.
[Show abstract][Hide abstract] ABSTRACT: In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings.
European Journal of Internal Medicine 09/2013; 25(2). DOI:10.1016/j.ejim.2013.08.700 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The 'real time' capability of ultrasound (US) allows dynamic assessment of joint and tendon movements, which can often aid in the detection of structural abnormalities. The simultaneous use of arthroscopy (AS) and US is therefore a logical progression. Here the results of a series of 11 patients with different rheumatic diseases in whom a combined use of US and AS was adopted are reported.
Expert Opinion on Medical Diagnostics 04/2013; 7(4). DOI:10.1517/17530059.2013.794136
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Early treatment of inflammatory arthritis (IA) leads to reduced disease activity, reduced joint damage, decreased functional impairment and increased chance of remission. However, delay often occurs from referral to rheumatology appointment. This survey evaluated whether a preliminary triage carried out by healthcare workers without formal medical training could be effective in identifying patients with or without early IA.
Patients were recruited during their first call to our centre, before their first visit. A simple questionnaire, including three questions and aimed at investigating the presence of sign and symptoms of IA was developed. The same survey was administered twice: the first time, during patient's first call to our centre (telephone survey), and the second time, during their first visit with the rheumatologist (Ambulatory visit survey). We compared the outcomes of the survey with the actual diagnosis made by the rheumatologist following standard medical examination.
In total 484 patients were included in the study, and 34/484 (7.02%) were confirmed to have early IA. The telephone survey was able to detect the non-early IA patients in 99.5% of cases; the same result was reported for the ambulatory visit survey. The median time required to complete the questionnaire was 1 minute in both surveys.
The adoption of a simple survey, also administered by non-medical personnel, may effectively contribute to the early detection of IA.
Clinical and experimental rheumatology 03/2013; 31(4). · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation.
The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc.
We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively.
Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR.
Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.
American heart journal 02/2013; 165(2):200-7. DOI:10.1016/j.ahj.2012.10.020 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients.
The study involved 20 patients (2 men and 18 women with a mean ± SD age of 52.96 ± 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age- and sex-matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels.
All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (β) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower (P = 0.0033) and plasma ADMA levels were higher (P < 0.0001) than in healthy controls.
SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.
Arthritis Care and Research 02/2013; 65(2):274-80. DOI:10.1002/acr.21819 · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This case series evaluates the clinical and ultrasound response to tocilizumab treatment in patients with rheumatoid arthritis (RA). Six patients with active RA (DAS28 ≥ 3.2) for ≥6 months, refractory to conventional DMARDs or anti-TNF agents, received tocilizumab 8 mg/kg every 4 weeks, as monotherapy or in combination with DMARDs, for 6 months. The following clinical parameters were assessed monthly: number of tender joints (28 and 44 joints), number of swollen joints (28 and 44 joints), DAS28-ESR, DAS28-CRP, VAS score, global health status, health assessment questionnaire, patient global assessment of disease activity, physician global assessment of disease activity, functional assessment of chronic illness therapy (FACIT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients also underwent a gray-scale ultrasonography (US) assessment with power Doppler evaluation at each visit. All clinical parameters improved during the study, versus baseline. This improvement was statistically significant for most parameters 2 months following tocilizumab initiation and was sustained to the end of the observation period. The number of tender joints (44-joint evaluation), the FACIT score, and ESR and CRP concentrations were significantly improved versus baseline values after the first month of tocilizumab treatment. The course of US evaluations mirrored that of clinical parameters; a faster and more evident response was observed for foot joints, with respect to hand joints. This case series suggested the rapid clinical benefit of tocilizumab. Ultrasound assessment showed that the onset of this effect was faster in the foot joints than in the hand joints.
Rheumatology International 01/2013; 34(5). DOI:10.1007/s00296-012-2638-3 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the last decade, treatment strategies for rheumatoid arthritis (RA) have included the early use of disease-modifying anti-rheumatic drugs, since prompt suppression of disease activity is associated with a reduction in radiological damage. This strategy has now been incorporated into the broader concept of "tight control", defined as a treatment strategy tailored to each patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. To pursue this goal, tight control should include careful and continuous monitoring of disease activity, and early therapeutic adjustments or switches should be considered as necessary. It is noteworthy that the key role of tight control of RA has been stressed by the recent EULAR Guidelines. This review discusses the most recent evidence concerning the role of a tight control strategy in the treatment of RA, and on how this strategy should be pursued.
[Show abstract][Hide abstract] ABSTRACT: Technological advances in ultrasonography (US) in recent years has allowed for improvements to the imaging quality of gray-scale ultrasound and the development of more advanced forms of this imaging technique such as 3D and Doppler US. These improvements mean that US now has an accepted place in rheumatology not only in diagnosis, but also in the determination of disease progression and pathology and in facilitating guidance of interventional therapies. The increasing use of US-guided intervention by rheumatologists in the last 20 years is evidenced by the almost exponential increase in the number of publications in the relevant subjects.
Rheumatology International 03/2012; 33(7). DOI:10.1007/s00296-012-2403-7 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Milwaukee shoulder is a well defined clinical entity that can be observed in particular in older women. It is a destructive arthropathy associated with the deposition of calcium pyrophosphate dihydrate crystals, characterized by the presence of large amount of synovial fluid and a complete tear of the rotator cuff. Clinical features include pain, swelling and progressive functional impairment. The first-line treatment include the use of analgesic drugs and repeated arthrocentesis followed by intra-articular steroid administration; closed-needle tidal irrigation has been reported to be useful. In late phase we can observe narrowing of the acromion-humeral and of the gleno-humeral joint and progressive degenerative changes at the humeral head, leading to almost complete functional impairment. In these cases a surgical approach with total shoulder arthroplasty may be considered.
[Show abstract][Hide abstract] ABSTRACT: To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA).
Thirty-two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal.
In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion.
We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission.
We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment. US indexes of grey scale (GS) and power Doppler (PD) synovitis were correlated with clinical evaluation, laboratory indexes and clinical outcome. Clinical remission was defined when DAS was <1.6 at two consecutive visits 3 months apart.
US examination was significantly more sensitive than clinical examination, both in active disease and in remission. In patients with an active disease, both clinical and US indexes correlated with CRP, whereas in remission only PD still remained significantly correlated. In clinical remission, 95% of the patients showed residual GS synovitis, and 41% of them showed a positive PD signal. Positive PD signal, even in a single joint, resulted the main predictor of relapse within 6 months, both in univariable and multivariable logistic regression analysis.
In a cohort of early RA patients treated with conventional DMARDs, US-GS can detect residual disease activity more sensitively than clinical examination both in active disease and in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing inflammation even during remission and predicts short-term relapse.