Management of psoriatic arthritis: a consensus opinion by expert rheumatologists.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA. Methods: A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: "early PsA," "axial-PsA," "extra-articular manifestations and comorbidities," "therapeutic goals." Relevant articles from the literature (2016-2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated. Results: Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for "early PsA"; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for "axial PsA"; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for "comorbidities and extra-articular manifestations"; target and tools, treat-to-target strategy, role of imaging for "therapeutic goals." The final document consisted of 49 statements. Discussion: The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Determining the PASS cut-off points for the FIQR, FASmod and PSD in patients with fibromyalgia: a registry-based study.

OBJECTIVES: To determine the cut-off values of Patient Acceptable Symptom State (PASS) for the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Scale (FASmod), and the Polysymptomatic Distress scale (PSD) and to determine the predictors of PASS in patients with fibromyalgia (FM). METHODS: FM patients belonging to the Italian Fibromyalgia Registry (IFR) completed the FIQR, the FASmod and the PSD. The PASS was assessed using a dichotomous answer. The cut-off values were obtained through the receiver operating characteristic curve (ROC) analyses. A multivariate logistic regression analysis was performed to determine predictors of achieving the PASS. RESULTS: 5545 women (93.7%) and 369 males (6.3%) were included in the study. The 27.8% of patients reported an acceptable symptom state. Patients in PASS differed in all patient-reported outcome measures (p <0.001). The FIQR PASS threshold was ≤58 (area under the ROC curve [AUC] = 0.819). The FASmod PASS threshold was ≤23 (AUC = 0.805) and the PSD PASS threshold was ≤16 (AUC = 0.773). In the pairwise AUC comparison, the discriminatory power of the FIQR PASS outperforms both FASmod PASS (p = 0.0124) and PSD PASS (p <0.0001). Multivariate logistic analysis showed that FIQR items related to memory and pain were the only predictors of PASS. CONCLUSIONS: The FIQR, FASmod, and PSD PASS cut-off points for FM patients have never been determined before. This study provides additional information to facilitate interpretation of the severity assessment scales in daily practice and clinical research related to FM patients.

The measurement of fibromyalgia severity: converting scores between the FIQR, the PSD and the FASmod.

OBJECTIVES: The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information. METHODS: 3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales. RESULTS: FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient. CONCLUSIONS: Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

Early characterization of difficult-to-treat rheumatoid arthritis by suboptimal initial management: a multicentre cohort study.

OBJECTIVES: To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). METHODS: In this retrospective multicentre cohort study conducted from 09/2021-03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000-2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. RESULTS: We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P < 0.001). In multiple regression, treatment delay beyond 3 months (OR 0.3; 95% CI 0.1, 0.9) and non-discontinuation of glucocorticoids after 6 months (OR 4.6; 95% CI 2.2, 9.5) were significantly associated with D2T-RA. Treatment delay was significantly associated with PIRRA only, while non-discontinuation of glucocorticoids was significantly associated with PIRRA and NIRRA. Results were replicated in sensitivity analyses. CONCLUSION: Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA.

Low-energy Pulsed Electromagnetic Field Therapy Reduces Pain in Fibromyalgia: A Randomized Single-blind Controlled Pilot Study.

Objectives: Fibromyalgia symptoms have a significant impact on the quality of life and respond poorly to medications. It has been hypothesized that the use of low-energy pulsed electromagnetic field (PEMF) induces neuroprotective effects that may interfere with pain perception. We explored the efficacy of PEMF in patients affected by fibromyalgia. Methods: Twenty-one females (median age 59 years, interquartile range [IQR] 16.5) affected by fibromyalgia were randomized to receive pulsed electromagnetic field-triple energy pain treatment (PEMF-TEPT) or placebo at T0 and at 4 weeks and 8 weeks. Fibromyalgia impact questionnaire (FIQ), widespread pain index (WPI), visual analog score (VAS) pain, symptom severity (SS) scale, and short form 36 (SF-36) health survey questionnaire have been evaluated. Results: Patients in the PEMF-TEPT group had a significantly higher reduction of WPI compared to placebo (mean difference -12.90 ± standard deviation [SD] 5.32 vs. -1.91 ± 4.55, difference in difference [DD] of -10.99; P < 0.001), of SS score (-4.10 ± 4.85 vs. -2.00 ± 2.32; DD = -2.1; P < 0.05), of VAS pain (-48 ± 30.75 vs. -16.82 ± 23.69; DD = -31.18; P < 0.01). They also reported a higher improvement of FIQ and SF-36, albeit not reaching statistical significance. Conclusion: In our pilot controlled study, PEMF-TEPT appeared to be safe and improved fibromyalgia symptoms.

Bone Involvement in Patients with Spondyloarthropathies.

Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.

Osteosarcopenia in Very Old Age Adults After Hip Fracture: A Real-World Therapeutic Standpoint.

Loss of bone and muscle mass and strength (i. e., osteosarcopenia) is a highly prevalent clinical condition in older adults, associated with an increased risk of fragility fractures and unfavorable clinical outcomes. Although sarcopenia is a potential risk factor for osteoporosis and subsequent fracture, and the management of this hazardous duet is the key to preventing osteoporotic fracture, evidence pertaining to the treatment of sarcopenia for the purpose of preventing fragile fractures remains insufficient. Given this scenario we aimed at prospectively compare the long-term effectiveness of bisphosphonates vs. denosumab, on bone and muscle, in a cohort of old age hip fractured patients by virtue of a timely osteo-metabolic and sarcopenic assessment. Ninety-eight patients consecutively enrolled at the IRCCS Hospital San martino, Genoa, Italy, received at baseline comprehensive geriatric assessment and Bone Densitometry (DXA) with the quantitative and quantitative bone analysis and evaluation of relative skeletal muscle index (RSMI) and longitudinally after 1 year form hip surgery. The results showed a slightly and non-significant osteo-metabolic improvement in the Alendronate group compared to the Denosumab group, and a positive trend of RSMI measurements in the Denosumab group. Although preliminary in nature, this is the first report to longitudinally analyze osteosarcopenia in a real-world cohort of very old age patients after hip fracture and moved a step forward in the understanding of the best osteo-metabolic therapy for long- term treatment, exploring as well the potential dual role of denousumab as antiresorptive and muscle strength specific drug for osteosarcopenia in this vulnerable population.

Olfactory dysfunction in antineutrophil cytoplasmic antibody-associated vasculitides: A review of the literature.

Olfactory dysfunction (OD) has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but the underlying mechanisms are not completely understood. The causes of altered smell function can generally be divided into conductive, sensorineural or others. To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored. The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV. Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.

Long-term methotrexate use in rheumatoid arthritis patients: real-world data from the MARTE study.

BACKGROUND: The MARTE study investigated the demographic, clinical, and therapeutic characteristics of rheumatoid arthritis (RA) patients ongoing methotrexate (MTX) treatment for longer than 8 years. METHODS: This cross-sectional, observational study considered 587 RA patients from 67 Rheumatology Units across Italy. Data collected included demographic, clinical, and therapeutic characteristics, focusing on MTX prescription patterns (route of administration, dosing regimens, treatment duration, and discontinuation). RESULTS: As initial therapy, 90.6% of patients received one conventional synthetic Disease Modifying Anti Rheumatic Drug (csDMARD), with treatment started within the first 3 months from diagnosis in half of the patients. MTX was the first csDMARD in 46.2% of patients. The prevalent route of administration at diagnosis was the intramuscular (60.5%), while at study entry (baseline) 57.6% were receiving subcutaneous MTX. Patients who required a higher MTX dose at study entry were those who received a significantly lower starting MTX dose (P<0.001). Significantly higher MTX doses were currently required in men (P<0.001), current smokers (P=0.013), and overweight patients (P=0.028), whereas patients on oral therapy received significantly lower doses of MTX (P<0.001). CONCLUSIONS: The MARTE study confirms once again the potential of the proper use of MTX in the treatment of RA. Data from our study suggest that a higher dose of MTX should be used since the first stages in overweight patients, men, and smokers.

A novel effervescent formulation of oral weekly alendronate (70 mg) improves persistence compared to alendronate tablets in post-menopausal women with osteoporosis.

BACKGROUND: A novel effervescent buffered solution of 70 mg alendronate (ALN-EX) was developed to improve upper gastrointestinal (GI) tolerability over alendronate tablets (ALN-T). Whether a better GI tolerability can improve persistence remains to be determined. AIM: This study evaluated persistence and reasons for discontinuation in patients treated with ALN-EX compared to a historical cohort on ALN-T. METHODS: Post-menopausal women (PMW) from a standardized clinical database with BMD T-score < -2.5, or between -2 and -2.5 and at least one vertebral fracture, starting ALN-EX between July 2015 and June 2016 were included. A historical cohort comprised of randomly selected and age-matched PMW on ALN-T was used as a control. Persistence at 6 and 12 months and reasons for discontinuation (e.g. adverse events; AE) were compared between the two groups. RESULTS: A total of 144 PMW on ALN-EX and 216 PMW on ALN-T were analysed. Persistence at 6 and 12 months was 91% and 81% in the ALN-EX group vs. 75% and 69% in the ALN-T group, this difference attaining statistical significance at both 6- (p < 0.001) and 12 months (p = 0.009). A significantly higher proportion of patients receiving ALN-T discontinued treatment due to GI AEs (4% ALN-EX vs. 11% ALN-T; p = 0.027), or patient's decision to discontinue (6% ALN-EX vs. 13% ALN-T; p = 0.016). The adjusted odds ratio of persisting on ALN-EX treatment at 12 months was 2.02 (95% CI: 1.21-3.41, p = 0.008). CONCLUSION: Our findings demonstrate that ALN-EX can provide greater persistence and improved tolerability compared to ALN-T, allowing it to be a viable alternative option in the management of osteoporosis.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study.

OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Zoledronate decreases CTLA-4 in vivo and in vitro independently of its action on bone resorption.

Acute phase response (APR) following intravenous zoledronate (ZOL) administration is related to activation and increased proliferation of γδ T cells, attributed to the molecular mechanism of action of nitrogen-containing bisphosphonates (N-BPs). ZOL, however, has also been reported to inhibit the proliferation of regulatory T cells in vitro and to reduce the expression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), a negative regulator of T cell activation that is increased in patients with autoimmune diseases. There are, however, no data on the relationship between ZOL treatment and soluble(s)CTLA-4 either in vivo in relevant patient populations or in vitro with the use of assays relevant to the mechanism of action of N-BPs. The objectives of the present study were firstly, to characterize the ZOL-induced APR in patients with inflammatory rheumatic diseases (IRDs) and its relationship with changes in circulating sCTLA-4 and secondly, to investigate the effects of ZOL on CTLA-4 production and expression by peripheral blood mononuclear cells (PBMCs). We studied 10 postmenopausal women with IRDs treated with intravenous ZOL 5 mg. Five women experienced APR (APR+) associated with significant decreases in blood lymphocytes and increases in granulocytes and serum CRP. Serum sCTLA-4 values were increased in all patients before ZOL administration and decreased significantly 72 h after the ZOL infusion (from 30.0 ± 2.9 to 6.3 ± 1.8 ng/ml; p < 0.001) with no differences between APR+ and APR- patients. Consistent with the results of the in vivo study, ZOL (1 µM) decreased the production of sCTLA-4 by 87% and 57% after 3 and 5 days in cultures of peripheral blood mononuclear cells (PBMCs) in vitro, respectively, and inhibited the expression of both cytoplasmic and membrane-bound CTLA-4. Our results reveal a novel immunoregulatory action of ZOL that is not related to its action on bone resorption but might be associated with reported clinically significant extraskeletal outcomes of ZOL treatment.

The role of surgery in antineutrophil cytoplasmic antibody-associated vasculitides affecting the nose and sinuses: A systematic review.

BACKGROUND: The ear, nose and throat region has been reported to be one of the commonest sites involved in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis diseases and often precedes the diagnosis of ANCA-associated vasculitis by many months. Although treatment for ANCA-associated vasculitis primarily requires systemic immunosuppressive therapy, there are specific indications for sinonasal surgery during the course of the disease process. The three major roles for surgery in sinonasal vasculitis are to aid diagnosis through biopsy, enable symptom relief and nasal reconstructive surgery consideration when in remission. PURPOSE: The aim of this systematic review is to provide an overview of the surgical procedures which can be performed in patients with ANCA-associated vasculitis presenting with sinonasal involvement. MATERIALS AND METHODS: A systematic literature search was performed for scientific articles on MEDLINE (PubMed Advanced MEDLINE Search) and EMBASE. The search included all articles up to April 2020. CONCLUSION: Surgical intervention during the active phase of ANCA-associated vasculitis disease can improve the patient's symptoms and enable histological diagnosis. The surgical decision to manage the nose requires a multidisciplinary approach involving the vasculitis specialist and the ear, nose and throat surgeon. Nasal reconstruction can be performed to restore form and function but only when the disease is in remission so as to maximise success and minimise complications.

Radiofrequency echographic multi spectrometry for the prediction of incident fragility fractures: A 5-year follow-up study.

PURPOSE: To investigate the effectiveness of the T-score values provided by Radiofrequency Echographic Multi Spectrometry (REMS) in the identification of patients at risk for incident osteoporotic fractures. METHODS: A population of Caucasian women (30-90 years), enrolled from 2013 to 2016, underwent dual X-ray absorptiometry (DXA) and REMS scans at axial sites. The incidence of fragility fractures was assessed during a follow-up period up to 5 years. Afterwards, patients with and without incident fractures were stratified in two age-matched groups with a 1: 2 proportion (Group F' and Group NF', respectively). The performance of REMS T-score in discriminating between the two groups was quantitatively assessed and compared with DXA. RESULTS: 1516 patients were enrolled and 1370 completed the follow-up (mean ± SD: 3.7 ± 0.8 years; range: 1.9-5.0 years). Fracture incidence was 14.0%. Age-matched groups included 175 fractured patients and 350 non-fractured ones, respectively (median age 70.2 [interquartile range: 61.0-73.3] and 67.3 [65.4-69.8] years, p-value ns). The groups resulted also balanced for height, weight and BMI (p-values ns). As expected, the differences in REMS T-score (for vertebral site, -2.9 [-3.6 to -1.9] in Group F', -2.2 [-2.9 to -1.2] in Group NF') and DXA T-score (-2.8 [-3.3 to -1.9] in Group F', -2.2 [-2.9 to -1.4] in Group NF') were statistically significant (p-value <0.001). Analogous results were obtained for femoral neck. Considering the T-score cut-off of -2.5, REMS identified Group F' patients with a sensitivity of 65.1% and specificity of 57.7% of (OR = 2.6, 95%CI: 1.77-3.76, p < 0.001), whereas DXA showed a sensitivity of 57.1% and a specificity of 56.3% (OR = 1.7, 95%CI: 1.20-2.51, p-value = 0.0032). For femoral neck, REMS sensitivity and specificity were 40.2% and 79.9%, respectively, with an OR of 2.81 (95%CI: 1.80-4.39, p < 0.001). DXA, instead, showed a sensitivity and specificity of 42.3% and 79.3%, respectively, with an OR of 2.68 (95%CI: 1.71-4.21, p < 0.001). CONCLUSIONS: REMS T-score resulted an effective predictor for the risk of incident fragility fractures in a population-based sample of female subjects, representing a promising parameter to enhance osteoporosis diagnosis in the clinical routine.

Correction to: Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts.

Following publication of the original article [1], it was brought to our attention that the AOSD Consensus Group was incorrectly tagged and therefore not searchable. The publishers apologize for this error.

Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Because of its rarity, clinical trials are inherently small and often uncontrolled. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion. METHODS: A panel of 10 experts (9 rheumatologists and 1 pediatrician) was established. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed on the MEDLINE (Pubmed), EMBASE, and BIOSIS databases through April 2018 to identify (1) differences and similarities between AOSD and pediatric Still's disease (systemic juvenile idiopathic arthritis [SJIA]) and (2) the efficacy and safety of IL-1 inhibitors in AOSD treatment. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. In the third step, the voting results were analyzed, and the statements were finalized. RESULTS: Eleven statements were developed. Forty-six of 67 rheumatologists (72%) participated in the Delphi process. A positive consensus was reached after the first round of voting and was full (> 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as the first and as a subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude response to another one. The lack of studies comparing early versus late treatment did not allow to draw conclusions; however, data from SJIA suggest a better response in early treatment. CONCLUSIONS: The Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies.

Pathogenesis, Diagnosis and Management of Polymyalgia Rheumatica.

Polymyalgia rheumatica is an inflammatory rheumatic disease of the elderly characterised by pain and stiffness in the neck and pelvic girdle, and is the second most common inflammatory rheumatic condition in this age group, after rheumatoid arthritis. Polymyalgia rheumatica can occur independently or in association with giant cell arteritis, which is the most common form of primary vasculitis. The diagnosis of polymyalgia rheumatica is usually based on clinical presentation and increase of inflammatory markers. There are no pathognomonic findings that can confirm the diagnosis. However, different imaging techniques, especially ultrasonography, can assist in the identification of polymyalgia rheumatica. Glucocorticoids are the cornerstone of the treatment of polymyalgia rheumatica, but they might be associated with different adverse events. A subgroup of patients presents with a refractory disease course and, in these cases, adding methotrexate as a steroid-sparing agent could be useful. In this review, we summarise the latest findings regarding the pathogenesis, diagnosis and management of polymyalgia rheumatica and try to highlight the possible pitfalls, especially in elderly patients.