Accuracy of power Doppler ultrasonography in the diagnosis and monitoring of idiopathic inflammatory myopathies.

OBJECTIVES: No clear-cut guidelines exist for the use of imaging procedures for the diagnosis of idiopathic inflammatory myopathies (IIM). The aim of the present study was to assess the diagnostic accuracy of power Doppler ultrasonography (PDUS) score in IIM patients compared with a control group and its usefulness during follow-up. METHODS: All patients evaluated in the Vasculitis and Myositis Clinic, Rheumatology Unit, University of Siena were prospectively collected. All patients underwent US examination of both thighs in axial and longitudinal scans, which were also performed twice (T1) or three times (T2). RESULTS: Forty-five patients with IIM (median [interquartile range] age 55 [45-66] years; 35 female) were enrolled. Receiver operating characteristic curves distinguished patients and controls based on ∑power Doppler (PD), ∑oedema, ∑atrophy and CRP. The best cut-off value for ∑PD was 0.5, ∑oedema 1.5, ∑atrophy 0.5 and CRP 0.22 mg/dl. In a logistic regression analysis, the variables that most influenced diagnosis of IIM were ∑PD and ∑oedema (P = 0.017 and P = 0.013, respectively). ∑Oedema was lower at T1 (P = 0.0108) and T2 (P = 0.0012) than at T0. Likewise, ∑PD was lower at T1 (P = 0.0294) and T2 (P = 0.0420) than at T0. Physician global assessment was lower at T1 (P = 0.0349) and T2 (P = 0.0035) than at baseline. CONCLUSION: Our findings show that PDUS is a reliable diagnostic tool in the differential diagnosis between inflammatory and non-inflammatory myopathies. Moreover, PDUS can be employed also during the follow-up of patients with IIM. A reduction in disease activity, measured by physician global assessment, led to a concomitant decrease in both oedema and PD, which was directly correlated with their rate of change. This underlines the close link between clinical assessment and PDUS findings, not only at diagnosis but also during monitoring.

Radiologist-rheumatologist multidisciplinary approach in the management of axial spondyloarthritis: a Delphi consensus statement.

OBJECTIVES: The aim of this study was to develop a Delphi consensus statement between rheumatologists and radiologists for the diagnosis and monitoring of axial spondyloarthritis (axial-SpA). METHODS: Following an extensive literature search to identify unmet needs and potential goals for a multidisciplinary approach, a scientific board comprising 28 Italian hospital-based rheumatologists (n=19) and radiologists (n=9) identified 8 "starting points", resulting in the development of 23 consensus statements covering issues from current practice guidelines to specific MRI protocols for the assessment of axial-SpA. Each participant anonymously expressed a level of agreement for each statement using a 5-point Likert scale (1="strongly disagree"; 5="strongly agree") via an online Delphi method.Total cumulative agreement (TCA) was defined as the sum of the percentage of response to items 4 ("agree") and 5 ("absolutely agree"). Consensus was defined as ≥80% total cumulative agreement for each statement. RESULTS: After the first round of voting (28 participants), positive consensus was reached for 28/31 (90.3%) statements. Statements without consensus (n=3) were discussed in a face-to-face plenary session prior to the second vote (28 participants). After the second round voting, positive consensus was attained for all 31 statements, with mean final TCA of 95.5% (range 82.1-100%). CONCLUSIONS: This Delphi consensus statement provides an aid to rheumatologists and radiologists for the diagnosis and monitoring of axial-SpA.

Magnetic resonance imaging of the sacroiliac joints in SpA: with or without intravenous contrast media? A preliminary report.

OBJECT: Active sacroiliitis based on magnetic resonance imaging (MRI) without intravenous (I.V.) contrast material injection is considered sufficient for the diagnosis of spondyloarthritis (SpA), according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. This work shows the added value of administering I.V. contrast material when evaluating the response to tumor necrosis factor (TNF) antagonists therapy, on the extension of bone marrow oedema (BMO) and pathological enhancement (osteitis/synovitis) in the sacroiliac joints (SIJs) on MRI. MATERIALS AND METHODS: Forty-three patients (25 females and 18 males, mean age of 54 ± 16.60 years, range 22-75 years) with a clinical diagnosis of SpA and active sacroiliitis at MRI with I.V. contrast material, were considered for a follow-up MRI after 6 months of TNF antagonists therapy. Disease activity was monitored by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. Descriptive statistics, Student's t test and Cohen's kappa were used. P < 0.05 was considered statistically significant. RESULTS: Thirty-eight patients were finally included in the study; 36 of them showed an improvement on clinical assessment after therapy. Score's difference (improvement) after treatment was calculated in the MRI sequences both with and without contrast agent (respectively, mean value and range 3.18, 0-12 with contrast and 1.63, 0-7 without contrast). This improvement was statistically significant in each group (P value of 7.097e-08 with contrast and 6.741e-06 without contrast), and there was a significant difference between the two group too (P-value of 8.598e-07). Cohen's kappa for dichotomous variables showed a better agreement between the post-contrast MRI findings and BASDAI (K = 0.53, agreement = 92.11%, P = 0.0001) than MRI without contrast and BASDAI (K = 0.11, agreement = 57.89%, P = 0.06). CONCLUSIONS: The evaluation of enhancement is a reliable tool for the assessment of the response to therapy in SIJs involvement in SpA, better than BMO; hence, it should be advised in the MRI of these patients.

Long-term safety of anti-TNF agents on the liver of patients with spondyloarthritis and potential occult hepatitis B viral infection: an observational multicentre study.

OBJECTIVES: The aim of the study was to retrospectively evaluate the long-term safety profile of anti-tumour necrosis factor (TNF)-α agents on the liver of patients with spondyloarthritis (SpA) and a previously resolved hepatitis B virus (HBV) infection. METHODS: Medical records from 992 consecutive outpatients receiving anti-TNF-α therapy between 2007 and 2015 were retrospectively reviewed. HBV infection was assessed evaluating HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to hepatitis B core (anti-HBc), and HBV-DNA levels. In patients with a previously resolved HBV infection, serum levels of aminotransferase (AST/ALT) were also assessed every three months, while HBsAg and HBV-DNA every six months. RESULTS: We identified 131 consecutive patients (70 males, 61 females) with SpA and resolved HBV infection. At baseline none of the patients were positive for HBV-DNA, and AST/ALT levels were within the normal range with no subsequent increase during the observational treatment period. None received antiviral therapy prior to or during anti-TNF drug administration. At the end of the follow-up period (75.50±33.37 months) no viral reactivation was observed in anti-HBc positive patients, regardless of anti-HBs positivity. During the whole follow-up, HBV-DNA was undetectable in all patients, HBsAg remained negative, and it was not necessary to discontinue biologic therapy because of liver damage. CONCLUSIONS: Our results confirm that pre-emptive antiviral prophylaxis may not be necessary routine, but strict monitoring for AST/ALT levels, as well as for changes in HBV serology and HBV-DNA remain necessary and seem a realistic and cost-effective approach to identify early viral reactivation.

Effects of tumor necrosis factor-α inhibitors in mothers and daughters concordant for HLA-B27-positive ankylosing spondylitis.

OBJECTIVES: Pharmacogenomics is considered as the new frontier to predict the response to treatments and it can also be based on the comparison of family members being treated for the same condition. No data are available on the impact of anti-tumour necrosis factor (TNF)-α therapies in members of the same family with ankylosing spondylitis (AS). METHODS: We describe three mother-daughter couples concordant for AS and HLA-B27, both treated with TNF-α inhibitors, for whom the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP were evaluated during a follow-up of 24 months. RESULTS: All patients manifested improvements of all scores, but the daughters had a more prominent effect achieving faster complete disease remission. CONCLUSIONS: We hypothesise that longer standing chronic inflammation and older age may cause a less prompt and effective response to treatment in SA when compared with their genetically related controls.

Drug retention rates and treatment discontinuation among anti-TNF-α agents in psoriatic arthritis and ankylosing spondylitis in clinical practice.

OBJECTIVE: The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice. METHODS: Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued. RESULTS: 268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P = 0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P = 0.0073) and PsA and PsA with predominant axial involvement (P = 0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate. CONCLUSIONS: In this cohort, anti-TNF-α therapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-α agent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.

Anti-Cytosolic 5'-Nucleotidase 1A in the Diagnosis of Patients with Suspected Idiopathic Inflammatory Myopathies: An Italian Real-Life, Single-Centre Retrospective Study.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies were proposed as a biomarker for the diagnosis of inclusion body myositis (IBM), but conflicting specificity and sensitivity evidence limits its use. Our study aimed to assess the diagnostic accuracy of anti-cN1A in a cohort of patients who underwent a myositis line immunoassay for suspected idiopathic inflammatory myopathies (IIM). We also assessed the agreement between two testing procedures: line immunoassay (LIA) and enzyme-linked immunoassay (ELISA). MATERIALS AND METHODS: We collected retrospective clinical and serological data for 340 patients who underwent a myositis antibody assay using LIA (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag et cN-1A (IgG) line immunoassay) and verification with an anti-cN1A antibody assay using ELISA (IgG) (Euroimmun Lubeck, Germany). RESULTS: The serum samples of 20 (5.88%) patients (15 females, 5 males, mean age 58.76 ± 18.31) tested positive for anti-cN1A using LIA, but only two out of twenty were diagnosed with IBM. Seventeen out of twenty tested positive for anti-cN1A using ELISA (median IQR, 2.9 (1.9-4.18)). CONCLUSIONS: Our study suggests excellent concordance between LIA and ELISA for detecting anti-cN1A antibodies. LIA may be a rapid and useful adjunct, and it could even replace ELISA for cN1A assay. However, the high prevalence of diseases other than IBM in our cohort of anti-cN1A-positive patients did not allow us to consider anti-cN1A antibodies as a specific biomarker for IBM.

Baricitinib retention rate: 'real-life' data from a mono-centric cohort of patients affected by rheumatoid arthritis.

Objectives: The aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection. Materials and methods: Patients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort's demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks. Results: Ninety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p < 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation. Conclusion: Our data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects.

Ultrasound guided corticosteroids sacroiliac joint injections (SIJIs) in the management of active sacroiliitis: a real-life prospective experience.

INTRODUCTION: Active sacroiliitis represents the hallmark of axial spondyloarthritis (axSpA) and manifests as inflammatory low back pain associated with morning stiffness (MS). Sometimes, the combination of non-steroidal anti-inflammatory drugs (NSAIDs) and biological disease modifying drugs (bDMARDs) proves unsatisfactory in achieving a remission. MATERIALS AND METHODS: We enrolled patients affected with active sacroiliitis confirmed via magnetic resonance imaging (MRI) and treated with a corticosteroid sacroiliac joint injection (SIJI) via ultrasound guidance. After SIJI, we evaluated visual-analogue scale (VAS) and MS pain changes. As controls, we selected axSpA patients starting bDMARDs. RESULTS: We enrolled 26 patients (mean age 55 ± 14 years; 25 females and 1 male; > 95% treated with NSAIDs; 46% on bDMARDs; 75.82 ± 123 months) and examined a total of 47 treated joints. We detected a 48% reduction in VAS pain after 24 h. Moreover, we observed a significant reduction (p < 0.0001) of VAS pain between the baseline and every subsequent follow-up visit. Further, a significant difference in VAS pain compared to the baseline in the controls was observed starting from week 12. There was a significant reduction in MS after 1 week due to SIJIs, while in the controls the first significant change from the baseline in MS was detected after 12 weeks. The efficacy of infiltrative therapy lasted up to 6 months: persistent VAS as well as MS pain reduction was observed. CONCLUSIONS: US-guided SIJI represents an effective and safe technique for patients who have active sacroiliitis yet are ineligible for biologic treatment or who experience unsatisfactory disease control despite receiving therapy.

Treatment of erosive osteoarthritis of the hands by intra-articular infliximab injections: a pilot study.

Our pilot study aimed to investigate the efficacy and tolerability of intra-articular (i.a.) injections of infliximab as a therapy for erosive osteoarthritis of the hands. Ten women with bilateral involvement of the hands and typical erosive osteoarthritis radiographic findings were enrolled and followed for 12 months. All the patients were refractory to conventional drugs. Treatment consisted in monthly i.a. injections of 0.2 ml of infliximab (0.1 mg/ml) in each affected proximal and distal interphalangeal joint of the most involved hand, identified on the basis of clinical and radiological examinations. The other hand was treated with physiological saline (control). The patients did not know which hand was receiving infliximab. Clinical response was evaluated at enrollment, after 6 and 12 months. Posteroanterior radiographs of both hands were obtained at baseline and 12 months later. At 6 months all the patients experienced relief from spontaneous pain and pain on lateral pressure in the hand treated with infliximab and these findings became statistically significant after 1 year. No important modifications were recognized in the hand treated with physiological saline. The anatomical lesion progression system radiological score indicated a reduction, even if not statistically significant, in the hand treated with infliximab and a tendency to slow worsening in the hand treated with physiological saline at 12-month follow-up. No local or systemic adverse reactions were recorded. Our study shows the symptomatic effect and a possible disease modifying action of i.a. infliximab in erosive osteoarthritis of the hands.

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study.

Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated. Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate. Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2-3.2, p = 0.005). Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature.

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG). We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission. We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.

Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker for measuring articular cartilage damage and/or the therapeutic efficacy of treatments.

Cartilage oligomeric matrix protein (COMP) is a tissue-specific noncollagenous protein that was first detected in the serum and the synovial fluid of patients suffering from rheumatic disorders, such as rheumatoid arthritis, reactive arthritis, juvenile chronic arthritis, and osteoarthritis. In this review, the authors consider serum COMP levels in different diseases and discuss their study of patients with rheumatoid arthritis treated with anti-TNF-alpha, to evaluate whether COMP is able to predict a rapid and sustained clinical response to these drugs. They observe that patients with high COMP levels have a lower ACR 70 response independently of the state of systemic inflammation, and conclude that COMP seems to have a pathogenetic role that is independent of the mechanisms regulating inflammatory processes.

Effectiveness of Adalimumab in Non-radiographic Axial Spondyloarthritis: Evaluation of Clinical and Magnetic Resonance Imaging Outcomes in a Monocentric Cohort.

The primary aim of the study was to evaluate the long-term effectiveness of adalimumab (ADA) in a cohort of non-radiographic axial spondyloarthritis (nr-axSpA), and the secondary aims were to identify predictive factors of response and evaluate radiological progression.We evaluated 37 patients (male/female: 12/25; mean age 49 ± 14; mean disease duration: 6.3 ± 5.8) with active nr-axSpA (Assessment of SpondyloArthritis International Society criteria), despite the treatment with ≥1 nonsteroidal anti-inflammatory drug for at least 3 months, initiating the treatment with ADA 40 mg every other week. Patients were treated for 24 months, and evaluated at baseline, 6, 12, and 24 months. Outcome measures included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index. Radiograph of the spine and sacroiliac joints and magnetic resonance of the sacroiliac joints were performed at baseline and according to the standard of assessment for the disease.The proportion of patients that achieved a BASDAI50 response at 6, 12 and 24 months was 51.3%, 70.3%, and 76.8%, respectively. Treatment was well tolerated with no unexpected adverse events and/or serious adverse events. All patients remained on treatment for 2 years, with a good compliance. We did not identify any predictive factor of response to therapy. Moreover, modified Stoke Ankylosing Spondylitis Spine Score and Spondyloarthritis Research Consortium of Canada scores showed a trend of improvement during the study period.ADA was effective on clinical and radiological outcomes at 2-year follow-up; thus, early treatment with ADA may prevent radiographic damage and be associated with low disease activity or remission. Moreover, data from this cohort study have confirmed safety and tolerability profile of ADA in nr-axSpA in the long term.