Fausto Salaffi

Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale.

Objectives. To determine the minimal clinically important difference (MCID) of changes in chronic musculoskeletal pain intensity that is most closely associated with improvement on the commonly used and validated measure of the patients global impression of change (PGIC), and to estimate the dependency of the MCID on the baseline pain scores.

Women, men, and rheumatoid arthritis: Analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

IntroductionGender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA).MethodsThe cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents.ResultsWomen had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies.ConclusionsIn this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.

Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis : A comparison with matched healthy controls

Background and aims: Health-related quality of life (HRQOL) assessment is receiving increasing attention as an outcome measure in osteoarthritis (OA). The aims of this study were to compare HRQOL among older adults aged 55 to 78 years with hip and/or knee OA with those without OA, and to assess the influence of selected variables (sex, body mass index, radiographic OA severity, educational level, comorbidities) on HRQOL. Methods: The generic Medical Outcome Study Short Form-36 item healthstatus questionnaire (SF-36) was administered to a cohort of 264 OA patients (105 with hip OA alone, 108 with knee OA alone, and 51 with both hip and knee OA) and 112 healthy controls. Results: Compared with the healthy controls, OA of the lower extremities has a detrimental effect on the eight-scale profile score, as well as on physical and mental summary measures of the SF-36. The most striking impact was seen in the physical measures “physical functioning”, “physical role” and “pain” (p<0.0001). No statistically significant differences in SF-36 scores were found among the three groups of OA patients. The physical and mental summary scales of the SF-36 were closely correlated (p<0.0001). One hundred and forty-five patients (54.9%) reported at least one chronic coexisting disease. There was a significantinverse association with measures of comorbidity (number of comorbidities and comorbidity index score) and both physical and mental summary scores of the SF-36 questionnaire. In patients with OA of the knee alone (but not in hip OA alone or hip and knee OA), the SF-36 pain score was inversely correlated with years of formal education (p=0.016). In addition, the impact of hip and knee SF-36 dimensions was not influenced by the degree of radiographic severity. Conclusions: Older adults with OA of the lower extremitiesundergo a significant impact on multiple dimensions of HRQOL, compared with healthy controls. The use of a generic measure of HRQOL such as the SF-36, in studies of OA where comorbidity is common, should be useful in characterizing the global burden of this disease.

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.

Ultrasonography in the evaluation of bone erosions

OBJECTIVE To demonstrate the diagnostic efficacy of ultrasonography in depicting erosions in patients with rheumatoid arthritis and to compare sonographic and radiographic findings. METHODS Sonographic images were obtained with an AU-4 Idea Esaote Biomedica (Genoa, Italy) equipped with a 13 MHz linear transducer. RESULTS The images reported in this essay are representative examples of the ability of ultrasonography to detect and characterise even minimal bone margin changes in rheumatoid arthritis. CONCLUSION Ultrasonography with very high frequency transducers can depict bone erosions in early target areas of bone resorption. However, further studies are needed to validate this technique and to evaluate the relation between sonographic findings and those obtained with other imaging techniques (standard radiology, magnetic resonance).

Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study

OBJECTIVE The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. DESIGN A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. RESULTS Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). CONCLUSIONS The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.

Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience

Objective: To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity. Method: Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health—visual analogue scale, disability index—Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves. Results: The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables. Conclusion: PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.

Power Doppler sonography monitoring of synovial perfusion at the wrist joints in patients with rheumatoid arthritis treated with adalimumab

Objective: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis. Methods: 48 wrists of 24 patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician’s global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists. Results: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman’s r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination. Conclusion: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.

Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee.

OBJECTIVE The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index is a tested questionnaire to assess symptoms and physical functional disability in patients with OA of the knee and the hip. We adapted the WOMAC for the Italian language and tested its metric properties in 304 patients with symptomatic OA of the knee. METHODS Three hundred and four consecutive patients, attending 29 rheumatologic outpatient clinic in northern, central, and southern Italy, were asked to answer two disease-specific questionnaires (WOMAC and Lequesne algofunctional index) and one generic instrument (Medical Outcomes Study SF-36 Health Survey-MOS SF-36). A sample of 258 patients was readministered the WOMAC 7-10 days after the first visit and the structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbachs alpha, reliability using intraclass correlation coefficients (ICCs), and construct and discriminant validity using Spearmans correlations, Wilcoxon rank sum test, and Kruskal-Wallis test. RESULTS All WOMAC subscales (pain, stiffness, and physical function) were internally consistent with Cronbachs coefficient alpha of 0.91, 0.81, and 0.84, respectively. Test-retest reliability was satisfactory with ICCs of 0.86, 0.68, and 0.89, respectively. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, supporting the concepts of convergent construct validity. Very high correlations were also obtained between WOMAC scores and Lequesne OA algofunctional index. WOMAC physical function, but not WOMAC stiffness and pain subscales, was weakly associated with radiological OA severity (P=0.03). Also, WOMAC pain score was inversely correlated (P=0.01) with years of formal education. Examination of discriminant validity showed that the scores on the WOMAC and SF-36 followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. CONCLUSION The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.

Immunogenicity and autoimmunity during anti-TNF therapy

The introduction of anti-tumour necrosis factor (TNF) agents for the treatment of rheumatoid arthritis (RA), Crohns disease (CD) or spondyloarthritis (SpA) has revolutionised the therapeutic approach to patients with active disease failing to respond to conventional therapy. However, some of the patients treated with selective TNF inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Furthermore, anti-phospholipid antibodies, which are mainly detected by means of anti-cardiolipin assays, have been found in RA patients receiving TNF blockers. There have also been a number of reports of the development of anti-drug antibodies, of which those against infliximab can interfere with the drugs pharmacokinetics (and therefore its effects), and may also cause acute and delayed infusion and injection site reactions. The onset of autoimmune diseases during biological treatment is rare, but it needs to be promptly recognised in order to plan appropriate patient management. The addition of an immunosuppressive drug can reduce the induction of anti-TNF antibodies.