Stefania Gasparini

The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a comparison with a selected sample of healthy people

BackgroundThe health-related quality of life (HRQL) is an important indicator of the burden of musculoskeletal disease. The Medical Outcome Study Short-Term 36 (SF-36) is the most used tool that evaluates HRQL as a subjective perception about psychological and physical limitations due to an underlying illness. The purpose of this study was to compare the HRQL scores among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) and a selected sample of health people and determine their relationship with measures of clinical condition.Methods799 patients (469 with RA, 164 with AS, 65 with axial PsA and 101 with peripheral PsA) accepted the invitation to participate. 1579 healthy controls were used for the comparison. We calculated scores for the eight SF-36 subscales, the Physical Component Summary (PCS) score, and the Mental Component Summary (MCS) score, according to published algorithms. Disease-related characteristics included disease duration, comorbidity, a measure for disease activity and for radiographic damage. The presence of comorbidity was ascertained through patients self-reports by the Self-Administered Comorbidity Questionnaire (SCQ). Comparison were performed with respect to sex and age, and s-scores were calculated for comparison with the norm. Multivariate analyses were used to assess the relationship between HRQL and radiographic damage, disease activity, and socio-demographic data.ResultsThe four inflammatory rheumatic diseases (IRD), compared to controls, significantly impaired all eight health concepts of the SF-36 (p < 0.0001) in both component PCS and MCS scores (p < 0.0001). Overall, the dimensions typically affected were physical functioning, limitations due to physical function, and bodily pain. The disease with the worst HRQL for those dimensions was RA. The multivariate analyses revealed that the physical component was influenced by a high disease activity and comorbidity. The severity of psoriatic lesions was associated with poor mental functioning in patients with PsA.ConclusionChronic IRD have a clearly detrimental effect on the HRQL in both sex and in age groups, and physical domain is more impaired than mental and social ones.

Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: Comparison of adalimumab, etanercept and infliximab in the GISEA registry

OBJECTIVE To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register. METHODS The study involved 2769 adult patients with long-standing RA (mean age 53.2±13.4 years; mean disease duration 9.0±8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN). RESULTS 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p=0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p=0.023) were strong and statistically significant predictors of infection. CONCLUSIONS Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent.

Disease activity in psoriatic arthritis: comparison of the discriminative capacity and construct validity of six composite indices in a real world.

Objective. To compare, “in a real world,” the performance of the most common composite activity indices in a cohort of PsA patients. Methods. A total of 171 PsA patients were involved. The following variables were evaluated: peripheral joint assessment, patient reported of pain, physician and patient assessments of disease activity, patient general health status, dactylitis digit count, Leeds Enthesitis Index, Health Assessment Questionnaire (HAQ), physical and mental component summary score of the Medical Outcome Survey (SF-36), Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). To measure the disease activity, the Disease Activity Score (DAS28-ESR and DAS28-CRP), Simple Disease Activity Index (SDAI), Composite Psoriatic Disease Activity Index (CPDAI), disease activity in psoriatic arthritis (DAPSA), and Psoriatic Arthritis Disease Activity Score (PASDAS) have been calculated. The criteria for minimal disease activity (MDA) and remission were applied as external criterion. Results. The ROC were similar in all the composite measures. Only the CPDAI showed less discriminative ability. There was a high degree of correlation between all the indices (P < 0.0001). The highest correlations were between DAPSA and SDAI (rho = 0.996) and between DAPSA and DAS28-CRP (rho = 0.957). CPDAI, DAPSA, and PASDAS had the most stringent definitions of remission and MDA category. DAS28-ESR and DAS28-CRP had the highest proportions in remission and MDA. Conclusions. Although a good concurrent validity and discriminant capacity of six disease activity indices were observed, the proportions of patients classified in the disease activity levels differed. In particular, the rate of patients in remission was clearly different among the respective indices.

Colour Doppler ultrasonography evaluation of vascularization in the wrist and finger joints in rheumatoid arthritis patients and healthy subjects

OBJECTIVES To evaluate the presence of blood flow by colour Doppler ultrasonography (CDUS) in the wrist and finger joints of rheumatoid arthritis (RA) patients and healthy subjects and to define a cut-off value of CDUS resistive index (RI). METHODS Forty-three patients with RA and 43 healthy controls were examined by CDUS. The wrists, second and third metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were evaluated in each patient and healthy subject. Spectral Doppler analysis was performed in order to characterize the type of flow and a mean RI was measured to define a cut-off level. The area under receiver operating characteristic curve was used to evaluate the screening methods performance. RESULTS Flow was detected in 219 of the 430 total joints (50.9%) of RA patients (111 in the wrists, 49 in the MCP and 30 in the PIP joints). Healthy subjects had a quantifiable flow in 45 of the 430 joints (10.5%) and, in particular, 39 (86.4%) in the wrist, 5 (11.14%) in the MCP and 1 (2.2%) in the PIP joints. The intra- and inter-reader agreements for the detection of Doppler signal were very good (kappa 0.82 and 0.89, respectively). Mean RI values were 0.72±0.06 in RA patients and 0.86±0.06 in healthy subjects (p<0.01). At cut-off point of RI<0.79 the sensitivity was 89.6% and the specificity was 78.8% (positive likelihood ratio 4.22). CONCLUSION DUS is a useful tool for the detection of abnormal blood flow in inflammatory joints of RA patients.

Development and validation of the self-administered Fibromyalgia Assessment Status: a disease-specific composite measure for evaluating treatment effect

IntroductionThe Fibromyalgia Impact Questionnaire (FIQ) is a composite disease-specific measure validated for fibromyalgia (FM), but it is rarely used in clinical practice. The objective was to develop and analyse the psychometric properties of a new composite disease-specific index (Fibromyalgia Assessment Status, FAS), a simple self-administered index that combines a patients assessment of fatigue, sleep disturbances and pain evaluated on the basis of the 16 non-articular sites listed on the Self-Assessment Pain Scale (SAPS) in a single measure (range 0 to 10).MethodsThe FAS index was constructed using a traditional development strategy, and its psychometric properties were tested in 226 FM patients (209 women, 17 men); whose disease-related characteristics were assessed by means of an 11-numbered circular numerical rating scale (NRS) for pain, fatigue, sleep disturbances and general health (GH), the tender point score (TPS), the SAPS, the FIQ, and the SF-36. A group of 226 rheumatoid arthritis (RA) patients was used for comparative purposes. Of the 179 FM patients who entered the follow-up study, 152 completed the three-month period and were included in the responsiveness analyses. One hundred and fifty-four patients repeated the FAS questionnaire after an interval of one week, and its test/re-test reliability was calculated. Responsiveness was evaluated on the basis of effect size and the standardised response mean.ResultsThe FAS index fulfilled the established criteria for validity, reliability and responsiveness. Factor analysis showed that SAPS and fatigue contributed most, and respectively explained 47.4% and 31.2% of the variance; sleep explained 21.3%. Testing for internal consistency showed that Cronbachs alpha was 0.781, thus indicating a high level of reliability. As expected, closer significant correlations were found when FAS was compared with total FIQ (rho = 0.347; P < 0.0001) and the FIQ subscales, particularly job ability, tiredness, fatigue and pain (all P < 0.0001), but the correlation between FAS and the mental component summary scale score (MCS) of the SF-36 (rho = -0.531; P < 0.0001) was particularly interesting. Test/re-test reliability was satisfactory. The FAS showed the greatest effect size. The magnitude of the responsiveness measures was statistically different between FAS (0.889) and the FIQ (0.781) (P = 0.038), and between the SF-36 MCS (0.434) and the SF-36 physical component summary scale score (PCS) (0.321) (P < 0.01).ConclusionsThe self-administered FAS is a reliable, valid and responsive disease-specific composite measure for assessing treatment effect in patients with FM.

Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

BackgroundThe main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA).MethodsForty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altmans 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model.ResultsAfter 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044).ConclusionsThese data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register

INTRODUCTION Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Clinical Value of Single Versus Composite Provocative Clinical Tests in the Assessment of Painful Shoulder

Objectives:The aims of the present study were to investigate the clinical value of the provocative clinical tests and propose a composite index for the assessment of painful shoulder, using ultrasonography (US) as reference method. Methods:Two hundred three patients with painful shoulder underwent both clinical and US evaluations. The physical examination was carried out performing the Hawkins, Jobe, Patte, Gerber, and Speed tests. Each test was included in a composite index namely, SNAPSHOT (Simple Numeric Assessment of Pain by SHOulder Tests). The US examination was performed by a rheumatologist experienced in US and blinded to clinical findings. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratio of each clinical test were calculated. The receiver operating characteristic (ROC) curve analysis was used to assess the performance of the composite SNAPSHOT index. Results:Sensitivity was low for the clinical diagnosis of all shoulder abnormalities. The highest sensitivity and smallest negative likelihood ratio were found for the Hawkins (63.88% and 0.50%) and Patte (62.21% and 0.52%) tests. Specificity was good for Speed (76.33%), Gerber (75.42%), and Patte (74.20%) tests. Patte and Speed tests were the most accurate (71.12% and 66.41%, respectively). The calculated area under the ROC curve related to the SNAPSHOT composite index was 0.881 ± 0.026. With an optimal cut-off point of 3, the sensitivity and specificity were 75.8% and 87.5%, respectively. Conclusion:The results of the present study showed that SNAPSHOT is a feasible, informative and quantitative composite index for the assessment of painful shoulder in the clinical setting.

Early videocapillaroscopic changes of the psoriatic skin after anti-tumour necrosis factor alpha treatment.

Tumour necrosis factor · (TNF-·) is thought to play a central role in the pathophysiology of psoriasis. Consistent with this finding, TNF-· blockers have been reported to be effective for the treatment of the disease. Infliximab, a chimeric human murine monoclonal anti-TNF-·neutralizing antibody of the IgG1Î isotype, has been employed with success in moderate to severe psoriasis and to treat refractory psoriatic arthritis or other spondylo-arthropathies, causing a successful and long-lasting clinical improvement [1–3]. Since capillary microscopy has been found useful in the evaluation of qualitative and quantitative information on the microcirculation of the psoriatic plaque [4], to provide more information on the effects of anti-TNF-· in psoriasis and to investigate changes of microvasculature at the site of lesional skin following infliximab treatment, we performed videocapillaroscopy (VCP) in a patient with psoriatic spondylo-arthropathy. A 31-year-old man with active psoriasis and psoriatic spondylitis who had failed to respond to conventional therapies was treated with infliximab. At the same instance, we evaluated the efficacy of treatment and, above all, the timeline of capillaroscopic changes in the lesional skin. Infliximab (5 mg/kg) was given intravenously at weeks 0, 2 and 6 and every 6–8 weeks in the course of the therapeutic schedule. Clinical measures included the Psoriasis Area and Severity Index, the Bath Ankylosing Spondylitis Disease Activity Index for spinal pain, the Bath Ankylosing Spondylitis Functional Index for functional assessment [3] and quality of life measurements (Health Assessment Questionnaire; table 1). A well-delimited psoriatic plaque of the 2nd right finger was chosen. VCP examination (Videocap Dietosystem, at magnifications of !100 and !200) was performed by means of a computerized videomicroscope equipped with an optic contact probe in two different areas of the same lesional skin. A drop of cedar oil was used to Table 1. Results of clinical measures in our patient throughout infliximab treatment

THU0121 Ultrasound in the assessment of carpal tunnel syndrome in patients with rheumatoid arthritis

Background Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). Ultrasound (US) has proven to represent a reliable tool for the diagnosis of CTS [1]. However, its role in the diagnosis of CTS in patients with RA has been poorly investigated. Objectives The aim of this study is to evaluate the US findings at carpal tunnel level in a cohort of patients with RA, focusing on those with a clinical diagnosis of CTS. Methods Patients with RA fulfilling the ACR/EULAR 2010 classification criteria were consecutively enrolled. The diagnosis of CTS was made according to the American Academy of Neurology practice parameter for CTS [2]. The MSUS assessment was carried out using a MyLab Twice (Esaote SPA) US system working with a 18–22 MHz linear probe. The power Doppler (PD) frequency was set between 7.5 and 11.3 MHz. The following grey scale (GS) US parameters were assessed at the carpal tunnel level: cross-sectional area (CSA) of the median nerve at the carpal tunnel inlet (at the level of the pisiform and scaphoid bones), presence of flexor tenosynovitis and palmar radio-carpal synovitis (both in GS and PD), presence of crystal macro-aggregates and marked bone profile irregularities. The median nerve was considered enlarged if its CSA was more than 12 mm2. We evaluated the presence of intra-neural PD signals at the carpal inlet and scored its entity (0=no PD signal, 1=one single vessel within median nerve, 2=two or three single or two confluent vessels and 3=more than three single or more than two confluent vessels). PD was considered “positive” if grade 1 or more was found. Results We included 40 RA patients. CTS was diagnosed in 19 out of 80 wrists (23.8%) and in 13 out of 40 RA patients (32.5%). Enlarged median nerve was found in 3 out of 19 wrists with CTS (15.8%) and in 6 out of 61 wrists without CTS (9.8%). Flexor tenosynovitis was found in 7 out of 19 wrists with CTS (36.8%) and in 5 out of 61 wrists without CTS (8.2%). Palmar radio-carpal synovitis was found in 2 out of 19 wrists with CTS (10.5%) and in 3 out of 61 wrists without CTS (4.9%). Crystal macro-aggregates were not detected in any of the scanned wrists. Marked bone profile irregularities were found in 2 out of 19 wrists with CTS (10.5%) and in 14 out of 61 wrists without CTS (23%). Positive intra-neural PD was found in 9 out of 19 wrists with CTS (47.4%) and in 9 out of 61 wrists without CTS (14.7%). Conclusions These preliminary results suggest that MSUS could be a useful tool in the diagnosis of CTS also in patients with RA. Intra-neural PD and flexor tenosynovitis were the most frequently MSUS abnormalities detected in RA patients with CTS. The inflammatory involvement of the tendinous and joint structures which are part of the carpal tunnel could lead to median nerve compression and CTS symptoms and should be considered in the MSUS assessment of CTS. References McDonagh C, Alexander M, Kane D. The role of ultrasound in the diagnosis and managment of carpal tunnel sindrome: a new paradigme. Rheumatology (Oxford). 2015 Jan;54(1):9–19.doi: 10.1093/rheumatology/keu275. Practice parameters for carpal tunnel syndrome (summary statement). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 1993;43:2406–9. Disclosure of Interest None declared