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Objective Preliminary data brought licensing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of JAK inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs). Methods Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE database until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial modelwas applied to calculate pooled OR and corresponding 95% CI. PROSPERO registration number is CRD42022324143. Results We have included 1 phase I, 21 phase II, 3 phase II-III and 36 phase III RCTs for a total of 19443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%, 95% CI 0.10—0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%, 95% CI 0.12—0.32) in the control group in a mean follow-up of 16.8 weeks. IMIDs patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82 [95% CI 0.43 – 1.56]). No statistically different results were seen in sub-analyses for each investigated IMIDs, drug and dosage. Conclusion JAKi do not increase thromboembolic risk compared with placebo in IMIDs patients enrolled in selected RCTs.

Medical cannabis (MC) describes the usually inhaled or ingested use of a cannabis plant or cannabis extract for medicinal purposes. The action of whole cannabis plants is extremely complex because their large number of active compounds not only bind to a plethora of different receptors but also interact with each other both synergistically and otherwise. Renewed interest in the medicinal properties of cannabis has led to increasing research into the practical uses of cannabis derivatives, and it has been found that the endocannabinoid system (particularly CB2 receptor activation) is a possible target for the treatment of inflammatory and the autoimmune diseases related to immune cell activation. However, in vivo findings still lack, creating difficulties in applying translational cannabinoid research to human immune functions. In this review, we summarized the main mechanisms of action of medical cannabis plant especially regarding the immune system and the endocannabinoid system, looking at preliminary clinical data in three most important autoimmune diseases of three different specialities: rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.

ObjectiveFibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/ clinical factors and symptom severity measures using a web-based registry of patients with FM.MethodsAdult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)).ResultsData relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared ( F 3.321, p< 0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p

Coined in 1975 by Resnick et al., diffuse idiopathic skeletal hyperostosis describes a systemic condition that is mainly characterized by flowing ossification of the spine and, less frequently, peripheral entheses. Its overall incidence is 6-12%, but it is more frequently observed in males than in females and subjects aged >50 years, and its increased prevalence in people aged >70 years suggests that the course of the disease begins between the third and fifth decade of life but its clinical manifestations do not appear until later. Its pathogenesis and etiology remain unknown, but it has been reported to be associated with a number of genetic, metabolic, and constitutional factors. The aim of this review is to describe the main features of the disease and stimulate research into its pathogenesis, prevention, and treatment.

Background:Up to 30% of Psoriasis (PsO) patients are prone to develop Psoriatic Arthritis (PsA). Agreement on how to identify PsO patients at risk of developing PsA is still lacking (1).Objectives:To identify predictors of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA).Methods:MEDLINE, EMBASE and COCHRANE databases were searched (up to February 22nd, 2020). The PICO framework (population = PsO patients; intervention = clinical, environmental, imaging and genetic features; comparator = not applicable; outcome = PsA development) was used to design searches and define the eligibility of studies for inclusion. The MA focuses on 3 major features as possible predictors: i) PsO skin and nail involvement; ii) musculoskeletal (MSK) complaints; iii) inflammation and structural damage detected by imaging (Table 1). The sample estimates of the relative risk were pooled only when the studies were homogeneous in terms of cohort of patients, follow-up, study design and metrics.Results:4698 articles were screened for eligibility, 110 underwent a full reading and 29 were finally included. Figure 1 shows the study flow-chart for article selection. Though pooling was judge not appropriate, 5/7 prospective studies significantly support a predictive value of PsA development in patients with severe PsO (n=174635). While the predictive value of nail involvement is not well defined (n=2202), the pooled estimate from two cohort studies (n=474) supports nail pitting as predictor of PsA (RR=2.14 [1.32; 3.46]). Moving to the MSK complaints, the risk of developing PsA is about two times greater in PsO with than without arthralgia (pooled RR: 2.15 [1.16, 3.99]) within 2 years. Lastly, PsO patients with inflammation or structural damage detected by imaging are nearly four times more likely to develop PsA within 1-2 years (pooled RR from 4 cohort studies (n=247): 3.72 [2.12; 6.51]) (Table 1). The incidence rate of PsA varies from 1.34 to 5.9/100 p-ys in PsO and from 10.9 to 12.5/100 p-ys in PsOAr.Table 1.Studies reporting the major features as possible predictors of PsA development.PsO skin – severityPsO nail involvementPsO nail lesionsVariablesRelative Risk [95%CI]Follow-upWilson, 2009PsO nail involvementHRadjusted: 2.24 [1.26; 3.98]13.1±8.8 ysFaustini, 2015PASI score + PsO nail involvement/σ= -0.18[-0.84; 0.48] RR: 0.95 [0.37; 2.47]1.2±0.2 ysEder, 2016PASI score PsO nail involvement Type of PsO nail lesionsHR (>20vsHRunadjusted: 1.36 [0.76; 2.45] HRunadjusted: 2.21 [1.24; 3.92]4.1±2.1 ysEder, 2017PASI score + Type of PsO nail lesionsHRunadjusted: 1.05 [1.01; 1.09] HRunadjusted: 1.98 [0.83; 4.74]3.8±2.1 ysLewinson, 2017PsO severity defined from medicationsHRadjusted (moderate/severe vs mild): 5.02 [4.18; 6.04]5.1 ysEgeberg, 2018PsO severity defined from medicationsRR (severe vs mild): 1.31 [1.18; 1.46]18 ysElnady, 2019PASI score + PsO nail Involvement/σ= 0.79[-0.37; 1.95] RR: 1.43 [0.38; 5.31]2 ysGreen, 2020PsO severity defined from medicationRR (severe vs mild): 2.79 [2.49; 3.13]5.8 ysMSK-complaintsVariablesIncident-PsA casesFollow-upFaustini, 2015ArthralgiaRR: 1.98 [0.75; 5.19]1.2±0.2 ysEder, 2017ArthralgiaHRadjusted: 2.59 [1.15; 5.88]3.8±2.1 ysZabotti, 2019ArthralgiaRR: 4.44 [0.54; 36.72]1.6±0.5 ysSimon D, 2020ArthralgiaRR: 2.04 [0.86; 4.86]2.4±1.5 ysSub-clinical inflammation or structural damage detected by imagingVariablesIncident-PsA casesFollow-upFaustini, 2015MRIRR: 2.10 [0.75; 5.90]1.2±0.2 ysElnady, 2019MSK-USRR: 5.38 [1.17; 24.63]2 ysZabotti, 2019MSK-USRR: 6.86 [0.83; 56.63]1.6±0.5 ysSimon D, 2020HR-pQCTRR: 4.32 [1.96; 9.55]2.3±1.4 ysConclusion:Arthralgia and inflammation and/or structural damage detected by imaging are predictive features, likely prodromal, of PsA development. PsO severity and nail pitting are clinical manifestations related to PsA development.Figure 1.References:[1]Zabotti A, et al. Curr Rheumatol Rep. 2020 May 16;22(6):24. doi: 10.1007/s11926-020-00891-x.Disclosure of Interests:Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Orazio De Lucia Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Garifallia Sakellariou Consultant of: AbbVie, Novartis, Alberto Batticciotto Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Gilberto Cincinelli: None declared, Ivan Giovannini: None declared, Luca Idolazzi Speakers bureau: Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: UCB, Gabriella Maioli Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Ilaria Tinazzi Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Daniel Aletaha Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: Not relevant for this type of study, Antonio Marchesoni Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Josef S. Smolen Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Annamaria Iagnocco Speakers bureau: not relevant for this type of study, Paid instructor for: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Dennis McGonagle Speakers bureau: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Grant/research support from: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD

ObjectiveThe role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database.MethodsThis cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41- 50 years, between 51-60 years, between 61-70 years, and =71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA).ResultsThe study included 2889 patients (199 males and 2690 females), mean age of 52.58 (+/- 11.82) years, with a mean FIQR score of 59.22 (+/- 22.98) and a mean FAS 2019mod of 25.50 (+/- 8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the =71 years category showed significantly higher scores (p

The development of biologics and small oral molecules has recently changed the scenario of pharmacologic treatment of systemic rheumatic diseases and it has become a real revolution. These drugs have innovative mechanisms of action, based on the inhibition of specific molecular or cellular targets directly involved in disease pathogenesis. This new scenario has lead to a regular update of the management recommendations of several institutions, such as those for Rheumatoid Arthritis treatment that address the use of conventional and biologic therapies including TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, IL-6 inhibitors (tocilizumab and sarilumab), biosimilars and small oral molecules (the JAK inhibitors tofacitinib and baricitinib). Monotherapy, combination therapy, treatment strategies (such as treat-to-target) and the targets of sustained clinical remission or low disease activity are the final goal of the guidelines for rheumatic patients management. In another condition represented by Axial Spondyloarthritis guidelines suggest to start first with non-steroidal anti-inflammatory drugs to improve lifestyle and reduce spine inflammation, but if this is not achieved in 2–4 weeks it is important to consider the use of local therapies (i.e. glucocorticoid injections) or to start biologic therapy such as TNF inhibitors and then eventually switching to another TNF inhibitor or swapping to IL-17 inhibitor. In the case of active Psoriatic Arthritis, guidelines suggest to start with non-steroidal anti-inflammatory drugs and even local glucocorticoid injections especially for oligoarthritis, then to start conventional therapies if lack of efficacy, and finally start biologics or small oral molecules in the presence of drugs toxicity, unfavorable prognostic factors and still active arthritis. In several cases, active Psoriatic Arthritis patients develop a complex clinical condition with comorbidities such as diabetes, inflammatory bowel disease and high risk of infections, and for this reason the American College of Rheumatology and the National Psoriasis Foundation have developed specific guidelines for their management. Biologic and new small molecules therapies are very expensive, but the availability of biosimilars offers the opportunity of reducing the treatment cost and significantly decreasing the cost of originators as well. In fact, we live in a period characterized by the need to rationalize costs of these drugs, to allow treating a higher number of patients and to maintain a homogeneous possibility of treatment choice. For these reasons, we need to follow scientific guidelines and patients' clinical conditions to choose the correct treatment, also based on the economic burden of therapies.

The role of interleukin-1 (IL-1) has been studied in many diseases, ranging from auto-inflammatory diseases to malignancies, and much has been discovered. There are currently four IL-1 inhibitors available, but only two have been approved in Europe: the receptor antagonist anakinra, and the IL-1b selective inhibitor canakinumab. The aim of this paper is to summarise the on- and off-label use of canakinumab (ILARIS®).

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response. AREAS COVERED: Authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6 . The material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv. EXPERT OPINION: IL-6 is one of the most prominent pro-inflammatory cytokines. Increased levels are recorded in COVID-19 patients, especially those with severe-to-critical disease. Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19. Since IL-6 is a druggable target for several inflammatory diseases, pharmacological blockers of the IL-6 signaling pathway were repurposed to blunt the abnormal SARS-CoV-2-induced cytokine release. Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of the disease in patients with hyperinflammation and no or limited organ damage. Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition.

Low-dose dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). We retrospectively analyzed the efficacy of high-dose dexamethasone in patients with COVID-19-related ARDS and evaluated factors affecting the composite outcome (death or invasive mechanical ventilation). From March 4th to April 1st 2020, 98 patients with COVID-19 pneumonia were included. Those who after at least 7 days from symptom onset presented a worsening of the respiratory function or of inflammatory biomarkers were started on intravenous high-dose dexamethasone (20 mg daily for 5 days, followed by 10 mg daily for 5 days). Most patients were males (62%) with a mean age of 69 years. Hypertension and cardiovascular disease (CVD) were prevalent. Following dexamethasone treatment, a significant improvement in PaO2/FiO2 (277.41 [178.5–374.8] mmHg vs. 146.75 [93.62–231.16] mmHg, p

Objective Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. Methods Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). Results A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P Conclusion Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

Background Agreement on how to identify psoriasis (PsO) patients at risk of developing psoriatic arthritis (PsA) is lacking. Objective To identify predictors, risk factors and incidence rate (IR) of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA). Methods MEDLINE, Embase, and Cochrane databases were searched. Cohort studies were used to assess the predictors, while case–control studies for PsA risk factor determination. Results We screened 4698 articles for eligibility, and 110 underwent a full reading and 26 were finally included. Among skin and nail phenotypes, PsO severity and nail pitting were selected as predictors of PsA development. Furthermore, PsO patients with arthralgia (pooled RR 2.15 [1.16; 3.99]) and/or with imaging-MSK inflammation (pooled RR 3.72 [2.12; 6.51]) were at high risk of PsA. Higher categories of BMI and a family history of PsA were other predictors. In outpatient-based cohort studies, the IR of PsA per 100 patient-years varied from 1.34 to 17.4. Limitations Despite the strength of the overall results, the heterogeneity and the number of the cohort studies could be considered a limitation. Conclusions This study provides a tentative profile of the PsO patient at risk of PsA and will help the design of PsA prevention trials. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00378-w.

Background Despite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, additional drugs are needed to improve care of this disease. JAK inhibitors (JAKinhibs) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA. Tofacitinib and Upadacitinib were recently approved for the treatment of PsA. Our aim was to assess the efficacy and safety of JAKinhibs for the treatment of PsA. Methods A systematic review of the literature was performed to identify RCTs by electronic search of MEDLINE and EMBASE database until April 2021. RCTs were considered eligible if included only patients with PsA treated with JAKinhibs. The pooled efficacy and safety outcomes were calculated by meta-analysis and expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic. Results Five RCTs for a total of 3293 PsA patients treated with different JAKinhibs or placebo were included (2 phase III studies on Tofacitinib, 1 phase II study on Filgotinib and 2 phase III studies on Upadacitinib). All the studies were judged at low risk of bias according to Cochrane criteria. JAKinhibs showed a significantly higher ACR20 response rate compared to placebo (OR 3.78, 95% CI 2.72–5.24, I^2 = 57%, random effect model).and were associated with a non-statistically significant higher risk of serious adverse events (OR 1.12, 95% CI 0.14–2.82, I^2 = 46%, random effect model). Conclusions This is the first systematic review that performed a comprehensive evaluation of the efficacy and safety of JAKinhibs for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKinhibs that appear to be effective and safe over placebo for the treatment of PsA.

COVID-19 represents a major challenge for researchers worldwide. Although the fine mechanisms that lead to the cell and tissue damage in patient infected by SARS-CoV-2 and that develop the disease are still unknown, the global effort to find a cure brought scientists worldwide to produce a considerable number of publications that are slowly disclosing how the virus works and how the human body responds to the infection. The development of the disease, in fact, seems to be related to both a direct damage of the virus on the cell or on particular structures in the tissue and how the immune system and the inflammatory process respond to the infection. Of particular interest is the finding of a peculiar feature of the disease leading to intussusceptive angiogenesis in the lungs of deceased patients that might represent an anatomopathological fingerprint of the same infection.

Almost totality of fibromyalgia patients complain of disturbed sleep, but to date, this topic is at the centre of many controversies. First of all, subjective sleep complaints can be found in all patients, but not all studies observed altered objective parameters when investigating sleep using polysomnography; therefore, currently, no disease-specific sleep alterations have been found. Secondly, sleep disturbances correlate with many fibromyalgia symptoms, and it is now known that the relationship between sleep and pain is bidirectional, but it is still not clear why the sleep of fibromyalgia patients is so disrupted. Putative mechanisms include alterations in the hormonal, neurotransmitter and immune systems, and in the autonomic nervous system. There are also no interventions that are both safe and effective for improving sleep in fibromyalgia patients; hence, treatment must be multidimensional and take into account the multiple causative factors and the frequent fibromyalgia comorbidities. First, it is necessary to adopt behavioural changes, including sleep hygiene practices and regular exercise; secondly, some pharmacological treatments can be tried, such as pregabalin, amitriptyline and very low dose cyclobenzaprine, which are frequently used to treat pain and sleep disturbances in fibromyalgia patients, whilst duloxetine and milnacipran are less effective on sleep. New promising drugs are sodium oxybate, cannabis and cannabinoids. The high frequency of sleep alterations and their complex relationship with other manifestations in fibromyalgia mean that physicians should specifically address them, in order to have a positive effect on patients’ quality of life.

Background:Fibromyalgia (FM) patients report chronic widespread pain, fatigue, cognitive difficulties and sleep disturbances, often associated with anxiety and/or depression (1). FM syndrome more frequently affects women and many papers describe gender-related differences in the perception, description and expression of pain (2), but up to now, the impact of gender on the clinical severity of FM is still a controversial topic.Objectives:The aim of this study was to analyse the data from a web-based registry of FM patients in order to detect a relationship between gender and disease severity.Methods:Adult patients with FM, diagnosed on the basis of the 2010/2011 American College of Rheumatology (ACR) diagnostic criteria (3), were recruited at 19 Italian rheumatology centres between November 2018 and April 2019. Those affected by other conditions that could interfere with the assessment of FM, e.g. psychiatric disorders, were excluded from the study. The severity of the disease was evaluated by validated FM-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR) (4), the modified Fibromyalgia Assessment Status (ModFAS) questionnaire (5), and the Polysymptomatic Distress Scale (PDS) (6). The data obtained were collected in the Italian Fibromyalgia Registry, an online registry created with the support of the Italian Society of Rheumatology (SIR).Results:We analyse data from 2.381 patients affected by FM, 2.184 females (91.7%) and 197 males. No significant differences in mean age, disease duration, or BMI between the two genders were reported. The women expressed greater disease burden as indicated by higher scores for each completed test: higher mean ModFAS score (25.23 ± 8.83 Vs 23.37 ± 9.22; p = 0.005), mean FIQR score (58.62 ± 23.22 Vs 51.68 ± 23.06; p Figure 1.Mean scores for each FIQR item by gender.Conclusion:Our findings demonstrate that women with FM are globally more impaired than men (even if some psychological aspects of the disease are comparable), thus reinforcing the idea that gender plays a role in symptoms and functional impairments associated with the disease.References:[1]Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311:1547-55.[2]Nascimento, et al. Gender role in pain perception and expression: an integrative review. BrJP. 2020; 3: 58-62[3]Wolfe F, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 2011;38:1113–22.[4]Burckhardt CS, et al. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728–33.[5]Salaffi F, et al. Diagnosis of fibromyalgia: comparison of 2011/2016 ACR and AAPT criteria and validation of the modified Fibromyalgia Assessment Status. Rheumatol 2020; 0:1-8.[6]Wolfe F, et al. Fibromyalgia prevalence, somatic symptom reporting, and the dimensionality of polysymptomatic distress: results from a survey of the general population. Arthritis Care Res. 2013; 65:777–85Disclosure of Interests:None declared.

Background:Despite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, there is a huge necessity of finding effective drugs for this disease. JAK inhibitors (JAKi) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA (1). Up to now Tofacitinib is the only JAKi approved by the European Medicines Agency (EMA) for the treatment of PsA but in the next few years the number of approved JAKi is expected to rise significantly.Objectives:To assess the efficacy and safety of different JAKi for the treatment of PsA.Methods:A systematic review of the literature was performed to identify randomized controlled trials (RCTs), by electronic search of MEDLINE and EMBASE database until October 2020. Studies were considered eligible if they met the following criteria: I) study was a RCT; II) only patients with PsA were included; III) JAKi was compared to placebo in addition to the standard of care. Two reviewers (FC and AZ) performed study selection, with disagreements solved by the opinion of an expert reviewer (AS). The outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic.Results:We identified 557 potentially relevant studies. A total of 554 studies were excluded based on title and/or abstract screening. Three RCTs for a total of 947 PsA patients treated with JAKi were included (2,3,4). Two were phase III studies on the efficacy and safety of Tofacitinib (OPAL Beyond and OPAL Broaden) and one was a phase II study on Filgotinib (Equator). All three studies were judged at low risk of bias according to Cochrane criteria (5). The primary efficacy outcome in all the studies was the number of patients who achieved the response rate of the American College of Rheumatology 20 score (ACR20). The outcomes evaluation was performed at 12 week for the Filgotinib trial and at 16 week for the Tofacitinib trials. We used for the main analyses the group of patients randomized to Tofacitinib 5 mg because this is the only dosage approved by the EMA for the treatment of PsA. JAKi showed a significantly higher ACR20 response rate compared to placebo (OR 3.54, 95% CI 1.76 - 7.09, I^2 = 74%). JAKi also showed a significantly higher ACR50 response rate (OR 3.36, 95% CI 2.22 - 5.09, I^2 = 0%), ACR70 response rate (OR 2.82, 95% CI 1.67 - 4.76, I^2 = 20%), PsARC response rate (OR 2.67, 95% CI 1.26 - 5.65, I^2 = 79%), PASI75 response rate (OR 3.15, 95% CI 1.61 - 6.15, I^2 = 45%) compared to placebo. JAKi were also associated with significantly better HAQ-DI (mean difference -0.23 95% CI -0.31 - -0.14) and fatigue, measured with FACIT-F (mean difference 3.54 95% CI 2.13 - 4.94). JAKi compared to placebo were associated with a non-statistically significant different risk of serious adverse events (OR 0.56, 95% CI 0.11 - 2.91, I^2 = 38%).Conclusion:This is the first published systematic review that performed a comprehensive and simultaneous evaluation of the efficacy and safety of JAKi for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKi, that appears to be effective and safe over placebo. The impact of these data on international clinical guidelines needs further investigation.References:[1]George E Fragoulis, et al. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis, Rheumatology, Volume 58, Issue Supplement_1, February 2019, Pages i43–i54[2]Mease P, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 2017; 377: 1537-50.[3]Gladman D, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 2017; 377: 1525-36.[4]Mease P, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2367–77.[5]Higgins JP, et Al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560Figure 1.ACR20 response rate of Jaki over PlaceboDisclosure of Interests:None declared.

Objective The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. Methods Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). Results We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P Conclusion The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

ObjectivesDactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score.MethodsAfter a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score.ResultsDACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score.ConclusionsThe novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

Marco A Cimmino,1 Massimiliano Parodi,1 Francesca Barbieri,1 Stefano Bombardieri,2 Giuseppe Zampogna,1 Annamaria Iagnocco,3 Alberto Batticciotto,4 Luca Maria Sconfienza,5,6 Luigi Sinigaglia,7 Fabrizio De Benedetti,8 Fabiola Atzeni,9 Piercarlo Sarzi-Puttini10 1Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; 2Rheumatology Unit, Santa Chiara Hospital, University of Pisa, Pisa, Italy; 3Academic Rheumatology Centre, Università degli Studi di Torino, Turin, Italy; 4Rheumatology Unit ASST-Settelaghi, Ospedale di Circolo – Fondazione Macchi, Varese, Varese, Italy; 5IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 6Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; 7Rheumatology Unit, G. Pini Hospital, Milan, Italy; 8Division of Rheumatology, IRCCS, Bambin Gesù Paediatric Hospital, Rome, Italy; 9Rheumatology Unit, University of Messina, Messina, Italy; 10Rheumatology Unit, L. Sacco University Hospital, Milan, ItalyCorrespondence: Piercarlo Sarzi-PuttiniReumatology Department, L. Sacco University Hospital, ASST Fatebenefratelli – Sacco, Via G.B. Grassi, 74, Milan 20157, ItalyTel +39 02 39042208Email piercarlo.sarziputtini@gmail.comObjective: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone.Methods: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated.Results: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (− 0.804± 1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and Ntotal (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in Ntotal*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients’ clinical parameters significantly improved from baseline until week 48.Conclusion: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann–La Roche; ACTRACE EudraCT No. 2009 012185-32).Keywords: tocilizumab, rheumatoid arthritis, wrist, synovitis, low-field MRI, dedicated MRI

Background:Fibromyalgia syndrome (FM) is characterised by a complex symptom spectrum, dominated by the presence of chronic widespread pain, fatigue and unrefreshing sleep. FM affects between 2 and 3% of the general population. It is a condition that mainly involves middle-aged women, although it is increasingly being diagnosed in younger people. The severity of symptoms can vary greatly between individual patients, and is influenced by many factors (e.g. sex, body mass index) [1]. To date, there is little information about changes in severity in accordance with patient age.Objectives:The aim of this study was to investigate variations in symptom severity in FM patients according to age categories.Methods:A cross-sectional study of adult FM patients diagnosed according to the American College of Rheumatology 2010/2011 criteria was performed. The case series was included from an Italian national registry [2]. Patients were grouped according to five age categories: 18-40 years, 41-50 years, 51-60 years, 61-70 years, over 71 years. Symptom severity was assessed through the revised Fibromyalgia Impact Questionnaire (FIQR) and domains, including FIQR physical function (items 1-9), FIQR health status (items 10-11), and FIQR symptoms (items 12-21). Between-group characteristics were analysed using one-way analysis of variance (ANOVA).Results:This study included a total of 2889 patients, 403 aged 18-40 years, 756 aged 40-50 years, 1035 aged 50-60 years, 528 aged 60-70 years, and 167 over 70 years, respectively. The mean (standard deviation [SD]) score of the total FIQR was 52.68 (11.82). Total FIQR and individual domains all showed a normal distribution. Analysing the data by age category, there were statistically significant differences between the categories for the total FIQR (p = 0.030). The age categories with the highest disease severity were those above 71 years (FIQR 62.14, SD 22.45), and between 51-60 years (FIQR 60.31, SD 22.89) (Table 1). Significant differences between age categories were also found for the domains physical function (p = 0.006) and health status (p = 0.012), but not for the domain symptoms (p = 0.164).Table 1.Mean values of FIQR total score and domains according to age categories.FIQR and domains18-40 years41-50 years51-60 years61-70 years≥71 yearsp*FIQR total, mean (SD)57.90 (21.76)59.25 (23.30)60.31 (22.89)57.13 (23.59)62.14 (22.45)0.030FIQR physical function, mean (SD)15.51 (7.56)16.44 (7.77)16.77 (7.51)15.96 (7.82)17.68 (7.26)0.006FIQR health status, mean (SD)11.19 (5.85)11.24 (5.99)11.49 (5.93)10.57 (6.11)12.21 (5.97)0.012FIQR symptoms, mean (SD)31.32 (10.48)31.56 (11.32)32.10 (11.01)30.68 (11.47)32.24 (11.34)0.164Abbreviations and legend. FIQR = revised Fibromyalgia Impact Questionnaire; SD = standard deviation; * = one-way analysis of variance (ANOVA).Conclusion:Distinguishing the disease severity in FM patients according to age categories, a bimodal distribution emerges, with the disease severity being greatest in patients over 71 years and in the 51-60 years decade. The main differences in severity, according to what can be detected through the FIQR, are attributable to the domains physical function and health status, which show higher scores in the two classes with higher severity.References:[1]Sarzi-Puttini P et al., Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol 2020; 16: 645–660.[2]Salaffi F et al., The Italian Fibromyalgia Registry: a new way of using routine real-world data concerning patient-reported disease status in healthcare research and clinical practice. Clin Exp Rheumatol 2020; Suppl 123: 65-71.Acknowledgements:Società Italiana di Reumatologia (SIR) and Italian Ministry of HealthDisclosure of Interests:None declared

Fibromyalgia (FM) is a chronic disorder whose symptoms of pain, fatigue, sleep disturbances and depression have a devastating effect on patients' lives as it limits their ability to engage in everyday working and social activities, and make it difficult to maintain normal relationships with family, friends and employers. None of the currently available drugs are fully effective against the whole spectrum of symptoms. The aim of this narrative review is to summarise the data relating to the new therapeutic options that have become available over the last few years. Areas covered: Increasing efforts by the pharmaceutical industry have led to the introduction of new investigational drugs and new formulations of older drugs, and studies have been carried out in order to investigate the possibility of using drugs that are currently used for other diseases. Expert opinion: Slight improvements in the health of FM patients treated with drugs targeting a range of molecular mechanisms have been observed, but there is still no single drug that is capable of offering substantial efficacy against all of the characteristic symptoms of FM. The identification of new and improved therapies for FM requires consideration of the heterogeneity of the condition, which suggests the existence of different patient subgroups, a relationship between central and peripheral aspects of the pathophysiology, and the need for combined treatment with drugs targeting multiple molecular mechanisms.

Background. The aim of our study was to evaluate the serum concentration of klotho in a cohort of systemic sclerosis (SSc) patients compared to that of healthy controls and to correlate its levels with the degree and the kind of organ involvement. Methods. Blood samples obtained from both patients and controls were collected and analysed by an ELISA test for the determination of human soluble klotho. Scleroderma patients were evaluated for disease activity through clinical, laboratory, and instrumental assessment. Results. Our cohort consisted of 81 SSc patients (74 females, mean age 63.9 ± 13.1 years) and 136 healthy controls (78 females, mean age 50.5 ± 10.7 years). When matched for age, serum klotho concentration significantly differed between controls and patients (p<0.001). However, in SSc patients, we did not find any significant association between serum klotho and clinical, laboratory, and instrumental findings. Lower serum levels of klotho were detected in 4 patients who were anticitrullinated peptide antibody (ACPA) positive (p=0.005). Conclusions. Our data show a lower concentration of klotho in the serum of SSc patients compared to that of healthy controls, without any significant association with clinical manifestations and laboratory and instrumental findings. The association between serum klotho and ACPA positivity requires further investigation.

Background: According to international recommendations, psoriatic arthritis (PsA) should be managed by a treat-to-target approach, but the identification of the best tool for defining the target of remission/low disease activity (LDA) is still controversial. Objectives: To evaluate and compare the rates of remission/LDA by comparing Disease Activity in PSoriatic Arthritis (DAPSA) score with Very Low Disease Activity (VLDA)/Minimal Disease Activity (MDA) criteria in a real-life multicentre cohort of PsA patients. Methods: We performed a cross-sectional analysis including the first consecutive 500 PsA patients evaluated in 8 Italian rheumatology centres since September 2017. The rates of patients achieving DAPSA remission/LDA and VLDA/MDA were calculated and compared by a chi-square test. The agreement between the two criteria sets was established by Cohen’s kappa. The proportion of patients with residual disease activity despite remission/LDA and VLDA/MDA was computed for: peripheral arthritis (number of swollen [SJ] or tender joints [TJ] ≥1), Leeds Enthesitis Index (≥1), number of dactylitis (≥1), Body Surface Area (BSA, ≥3%), Patient Global Assessment (PGA, ≥20), Health Assessment Questionnaire (HAQ, ≥0.5), pain VAS (≥15), C-reactive protein (CRP, ≥1 mg/dL). Sub-analyses after stratification according to ongoing treatment (csDMARDs versus bDMARDs) were also performed. Results: The study population (53.2% men; mean [± standard deviation, SD] age 52.9±12 years; mean [±SD] disease duration 8.6±7.7 years) included 200 patients treated with csDMARDs (71% methotrexate) and 300 with bDMARDs (73% anti-TNF agents). The rates of DAPSA remission and VLDA were similar in the overall population (25.8 vs 22.2%, respectively; p=0.18) and in bDMARD subgroup (27.3 vs 26.7%, respectively; p=0.85), but greater for DAPSA remission in csDMARD patients (23.5 vs 15.5%, respectively; p=0.04). DAPSA LDA was significantly more frequent than MDA (40.6 vs 26.4%, respectively; p Conclusion: In our real-life cross-sectional analysis, the agreement between DAPSA and VLDA/MDA criteria was good only for the definition of remission, whereas DAPSA was significantly less stringent than MDA (especially in csDMARDs treated patients) in defining LDA, with a great proportion of patients showing residual arthritis and disability. Disclosure of Interests: Ennio Giulio Favalli: None declared, Luca Idolazzi: None declared, Serena Bugatti Speakers bureau: Bristol-Myers Squibb, Celgene, Lilly, Novartis, Sanofi, Janssen, Alberto Batticciotto: None declared, Luca Quartuccio: None declared, Matteo Filippini: None declared, Simone Parisi Speakers bureau: Chiesi, Jansenn, Pfizer, Celgene, Abbvie, Lilly., Martina Biggioggero: None declared, Angelo Fassio: None declared, G Zanframundo: None declared, Giuliana Guggino Grant/research support from: Laborest, Pfizer, Consultant for: Novartis, Abbvie, Speakers bureau: Sandoz, I Giovannini: None declared, Maria Chiara Ditto: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN

ObjectiveNon-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition.MethodsA cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development.ResultsTenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, pConclusionTenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.

Introduction: Pregabalin is indicated for the treatment of fibromyalgia and pregabalin-treated subjects have shown improved pain, sleep and functional measures in placebo-controlled and open-label studies. This article reviews pregabalin’s safety profile.Areas covered: The safety findings in pregabalin clinical trials were accessed by a PubMed search using the key words ‘pregabalin’ or ‘anti-epilectics drug’ or ‘gabapentinoids’ or ‘anticonvulsants’ and ‘fibromyalgia’. Although frequent, the side effects of pregabalin therapy are usually mild to moderate, well tolerated in the long term, and can be monitored in a primary care setting.Expert opinion: Pregabalin therapy may be associated with somnolence, dizziness, weight gain and periphereal edema. Potential drug interactions are not common, and pregabalin seems to be well tolerated in combination with antidepressants. The demonstrated efficacy of pregabalin suggests that the risk/benefit ratio favours its use.

Biosimilar infliximab (INX) was recently approved by the European Medicine Agency for the treatment of rheumatoid arthritis, ankylosing spondylitis (AS), Crohn’s disease, ulcerative colitis, psoriatic arthritis (PsA), and psoriasis on the grounds that its pharmacokinetics, safety, and efficacy were comparable to those of innovator INX. The aim of this study was to investigate the real-life efficacy, safety, and immunogenicity of switching from innovator to biosimilar INX in patients with spondyloarthritis (SpA). Forty-one patients attending three Italian rheumatology centres with a previous diagnosis of SpA and clinically inactive or moderate disease activity (ASDAS-CRP < 2.1; 22 with AS, five with enteropathic arthritis, 10 with PsA, and four with undifferentiated SpA), who had been treated for more than 6 months with innovator INX in accordance with the ASAS/EULAR guidelines, were switched to biosimilar INX for pharmaco-economic reasons (Tuscany Law No. 450 of 7 April 2015) and followed up for 6 months. A record was kept of their BASDAI, BASFI, ASDAS-CRP, DAS28-CRP (in the presence of peripheral disease), MASES, VAS pain scores, the duration of morning stiffness, and adverse events (AEs). At the time of the switch, the patients had a median age of 50.9 years (range 23–80), a median disease duration of 124.5 months (range 14–372), and a median duration of treatment with innovator INX of 73.7 months (range 6–144). After 6 months of biosimilar INX therapy, there were no statistical differences in their median BASDAI (2.73 ± 1.5 vs. 2.6 ± 1.3, p = .27), BASFI (2.34 ± 1.3 vs. 2.17 ± 1.2, p = 0.051), ASDAS-CRP (1.35 ± 0.3 vs. 1.28 ± 0.2, p = 0.24), DAS28-CRP (2.66 ± 0.67 vs. 2.67 ± 0.35, p = 0.92), MASES (0.35 ± 0.7 vs. 0.17 ± 0.4, p = 0.08), or VAS pain scores (18 ± 14.7 vs. 16.7 ± 11.3, p = 0.55), whereas the median duration of morning stiffness had significantly decreased (7.2 ± 6.9 vs. 5.8 ± 6, p = 0.02). Furthermore, there was no change in circulating INX (4.22 ± 2.89 vs 4.84 ± 2.86 μg/mL, p = 0.80) or anti-INX antibody levels (27.76 ± 17.13 vs 27.27 ± 17.28 ng/mL, p = 0.98). The switch from innovator to biosimilar INX in this Italian multicentre SpA cohort was not associated with any statistically significance differences in efficacy, adverse events or anti-drug antibody level.

Fibromyalgia is a chronic disorder whose symptoms have a devastating effect on patients' lives as they limit their ability to engage in everyday working and social activities, and make it difficult to maintain normal relationships with family, friends and employers. None of the currently available drugs are fully effective against the whole spectrum of symptoms of pain, fatigue, sleep disturbances and depression, but increasing efforts by the pharmaceutical industry have led to the introduction of new investigational drugs and new formulations of older drugs, as well as studies of the possibility of applying drugs currently used for other diseases. The aim of this review is to summarise the data relating to the new therapeutic options that have become available over the last few years.

Background:Enthesis anatomy and biomechanics have a key role in Spondyloarthritis (SpA) pathogenesis (1) but few data are available about the influence of structural and biomechanical changes of Achilles tendon (AT) on persisting pain in longstanding SpA patients.Objectives:To correlate AT pain in longstanding SpA patients with ultrasonographic detectable disorders and biomechanical abnormalities.Methods:We performed a monocentric cross-sectional analysis including 35 consecutive patients affected by SpA (13 with Psoriatic Arthritis, 9 with Enteropathic SpA, 6 with Ankylosing Spondylitis and 7 with Undifferentiated SpA) under treatment with anti- TNF agents. A rheumatologic clinical and clinimetric evaluation (AT VAS pain, BASDAI, BASFI, HAQ), an ultrasound study of AT according to the Madrid Sonographic Enthesis Index (MASEI) score and a podiatrist biomechanical evaluation [Foot posture index (FPI), degree of ankle dorsiflexion with the knee extended and flexed] were performed.Results:Study population (13 F; 22 M; mean age 54.9 ±13.9 years; mean disease duration 9.5 ± 5.0 years; mean BMI 25.8 ±4.4) showed a mean AT VAS pain of 3.4 ± 2.2, a mean HAQ of 0.6 ± 0.6, a mean BASDAI of 3.3 ±2.1 and a mean BASFI of 2.2 ±1.9. At the ultrasonographic evaluation 47% (33/70) of the AT entheses analysed presented a dishomogeneous echostructure, 31% (22/70) structural thickness, 53% (37/70) calcifications, 10% (7/70) erosions, 44% (31/70) a retrocalcanear bursitis. A power Doppler positivity was found only in 0.07% (5/70) of the AT.At the biomechanical evaluation 50% (35/70) of the feet showed a FPI score between 0 and + 5 (neutral foot), 46% (32/70) a FPI score between +6 and +9 (slight foot pronation) and 6% (4/70) a FPI score between -1 and -4 (slight foot supination).The mean degree of ankle dorsiflexion with extended knee was 8.4 ± 3.9 with the 61% (43/70) of the patients with a maximum dorsiflexion < 10° of whom 46% (20/43) do not recover after the knee flexion.We found a between the mean degree of left ankle dorsiflexion with extended/flexed knee both with ultrasound-revealed left AT enthesis calcifications (p=0.014/0.037) and with left AT enthesis thickness (p=0.049/0.035), and a significant association between the mean degree of right ankle dorsiflexion and extended/flexed knee and ultrasound-revealed right AT calcifications (p=0.008/0.012). Moreover, we noticed an inverse correlation between the mean overall degree of ankle dorsiflexion with extended/flexed knee and the BASFI values (p=0.007/0.004). AT VAS pain was statistically related with Achilles PDUS signal persistence (p=0.048) but not with US signs of chronic entesopathy or biomechanical alterations [calcification (p=0.39), erosions (p=0.74)]. The limits of the study were the low number of patients recruited and the lack of a control group.Conclusion:In this monocentric study on a cohort of SpA patients, we demonstrated a statistically significant correlation between ankle–subtalar joint complex biomechanics alterations, ultrasonographic signs of chronic enthesopathy and clinimetric index of functional disability. Residual Achilles pain seems to be related to US signs of active enthesitis.References:[1]The enthesis organ concept and its relevance to the spondyloarthropathies. Benjamin, M and McGonagle, D. s.l.: Adv Exp Med Biol, 2009, Vol. 649.[2]The Synovio-entheseal Complex and Its Role in Tendon and Capsular Associated Inflammation. McGonagle, E D, Aydin, SZ and Tan, AL. 0, s.l.: J Rheumatol Suppl, 2012, Vol. 89Disclosure of Interests:None declared

To correlate the expression of microRNAs (miRNAs) 146a/b, 16, the 17-92 cluster and 181a in salivary and plasma samples taken from primary Sjögren's syndrome (pSS) patients with clinical, laboratory and ultrasound findings.Plasma and salivary samples were collected from 28 patients with pSS according to 2012 ACR and/or 2016 ACR/EULAR criteria (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years), and from 23 healthy subjects used as controls. The following patient data were recorded: ESSDAI and ESSPRI scores, anti-SSA and anti-SSB antibody status and laboratory data, Schirmer's test, ultrasound scores of the four major salivary glands according to Cornec et al., and concomitant treatments. The retro-transcribed and quantified miRNAs were: miR16-5p, miR17-5p, miR18a-5p, miR19a-5p, miR19b-1-5p, miR20a, miR92-5p, miR146a-5p, miR146b-5p, miR181a-5p.SS patients had higher expression of salivary miR146a than gender- and age-matched controls (p=0.01). Spearman's regression analysis revealed that salivary miR146b was significantly more expressed in the patients with worse ESSPRI scores (p=0.02), whereas salivary miR17 and 146b and plasma miR17 expression was lower in the patients with higher ultrasound scores (respectively p=0.01, p=0.01 and p=0.04). Salivary miR18a expression was significantly increased in the patients who were anti-La/SSB positive (p=0.04). Neither salivary nor plasma miRNAs correlated with disease duration or concomitant therapies.Our data show that salivary mi146a may represent a marker of the disease, and that the expression of salivary miR17, 18a and 146b may be altered in patients with pSS, and associated with worse ultrasound and ESSPRI scores and anti-La/SSB positivity.

Background Enteropathic arthritis (EA) belongs to the spondyloarthritis (SpA) spectrum of diseases and occurs in patients affected by inflammatory bowel diseases (IBD). Several works demonstrated that ultrasonography (US) is a feasible, reliable and easily accessible tool for detecting chronic and active entheseal abnormalities even in a subclinical contest in SpA patients.1,2 Objectives To evaluate the prevalence of US entheseal involvement of the distal insertion of patellar ligament in patients affected by EA. Methods Twenty-two consecutive AE patients (12 with Crohn’s disease and 10 with ulcerative colitis; 8 females and 14 males; mean age 44.7 years, range 18–72 years; mean AE duration 10.1 years range 4–21 years) and 18 healthy age- and gender-matched controls (8 females and 10 males; mean age 48 years, range 24–68 years) underwent an US examination (ESAOTE MyLAB 70 6–18 MHz linear array transducer) according with the validated Madrid Sonographic Enthesis Index (MASEI). Clinical and clinimetric variables were assessed in both groups according with daily clinical practice. Results Focusing on the 44 distal patellar entheses we identified a higher prevalence of all the elementary lesion analysed. In 34 entheses we identify a dishomogeneous echostructure (77.3% vs 33.3%; p=0.0001), in 38 structural thickness (86.4% vs 66.7%; p=0.03), in 16 power Doppler positivity (36.3% vs 16.7%; p=0.04), in 17 presence of calcifications (38.6% vs 16.7%; p=0.03) and in 8 entheses the presence of erosions (18.8% vs 0%; p=0.007). In the 45% of the examined patients we detected a simultaneous presence of dishomogeneous echostructure, structural thickness and power Doppler positivity suggestive for US active enthesitis at the level of the same enthesis. Conclusions US detectable signs of enthesopathy and enthesitis are very frequent in EA patients even when we analyse the distal enthesis of the patellar ligament alone. Further studies involving a larger number of patients are needed to confirm these preliminary data. References [1] Atzeni F, Defendenti C, Ditto MC, et al. ”Rheumatic manifestations in inflammatory bowel disease”. Autoimmun Rev. 2014Jan;13(1):20–3. [2] Wakefield RJ, Green MJ, Marzo-Ortega H, et al. Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease. Ann Rheum Dis2004;63(4):382–5. Disclosure of Interest None declared

Background Identify the preclinical phase of arthritis could be clinically relevant. In this scenario, musculoskeletal ultrasonography (US) may play an important role, since it may detect subclinical disease. Psoriatic Arthritis (PsA) is a perfect disease to identify risk factors, since the risk pool group [i.e. patients with only cutaneous Psoriasis (Pso)] is known. Objectives To evaluate in Pso patients, with and without clinical arthralgia (CA), defined by the presence of joint pain without other clinical evidence of musculoskeletal inflammation: I) the prevalence of subclinical US inflammation in joints, enthesis, tendons and bursae; II) the prevalence of US structural damage; III) the relationship between US lesions and clinical data. Methods Cross-sectional prevalence study of US abnormalities in Pso patients with or without CA and healthy controls (HCs). Inclusion and exclusion criteria (e.g. osteoarthritis and fibromyalgia) are pre-defined. Forty-four joints (MCP, PIP and DIP joints, wrists, knees, MTP joints) and 12 enthesis (achilles, quadriceps, proximal and distal patellar, plantar aponeurosis and common extensor tendon enthesis) were scanned in each patient. US scans were performed using a ESAOTE MyLabClassC equipped with a high frequency linear probe. Active synovitis was defined by the presence of a grade ≥2 for grey scale (GS) and ≥1 for PD, while active enthesitis if there was hypoecogenity in GS and an entheseal PD signal (≤2 mm from bone insertion). Results Sixty-four Pso patients and 21 HCs were included; globally 2816 joints and 768 entheses were scanned. Twenty-three out of 64 (35.9%) Pso patients displayed CA. Baseline characteristics are reported in table 1. Active synovitis was found, in at least one joint, in 20/64 (31.3%) Pso patients and 0/21 HCs (p=0.002), while active enthesitis in 14/64 (21.9%) Pso patients and 0/21 HCs (p=0.017). No significant differences were found for active synovitis or enthesitis between the two subgroups of Pso, with or without CA. In the Pso cohort, 5/23 (23.8%) patients with CA and 2/41 (5%) without CA displayed tenosynovitis or paratenonitis (p=0.042). Furthermore, active synovitis, as well as GS-synovitis ≥2, was associated with higher NAPSI (9.7±8.0 vs 4.6±7.1, p=0.04 for GS ≥2), whereas active enthesitis was associated with higher PASI (5.4±3.0 vs 3.7±2.9, p=0.02). No significant differences were found between Pso patients and HCs for the structural damage (i.e. osteoproliferation and erosions), both for joints and enthesis. Conclusions In Psoriasis subclinical US active synovitis and/or enthesitis are present in 20%–30% of patients. In Pso the comparison between groups, with or without CA, show no significant difference in active subclinical synovitis or enthesitis, but Pso patients with CA present more frequently US tenosynovitis or paratenonitis. In Pso subclinical US synovitis or enthesitis are significantly associated with higher NAPSI and PASI. The relevance of these results, to possibly identify a subgroup of Pso more prone to develop PsA, deserve further investigation and prospective evaluation. Disclosure of Interest None declared

Background Fibromyalgia Syndrome (FM) is a persistent and debilitating disorder estimated to impair the quality of life of 2%–4% of the population. FM is an important representative example of central nervous system sensitisation and is associated with abnormal brain activity. The syndrome is still elusive and refractory. Hyperbaric oxygen therapy (HBOT) can rectify abnormal brain function underlying the symptoms of FM patients. Increasing oxygen concentration by HBOT may change the brain metabolism and glial function to rectify the FM-associated brain abnormal activity.1 Objectives To evaluate the effect of HBOT on clinical symptoms in FM resistant to the usual pharmacological treatment Methods Thirty female patients, aged 21–67 years and diagnosed with FM at least 2 years earlier, and resistant to any pharmacological treatment were assigned to be added on with HBOT. The treated group patients were evaluated at baseline and after 10 and 20 HBOT sessions. Evaluations consisted of physical examination, including tender point count, extensive evaluation of quality of life. Study endpoints included assessments of pain (VAS), the FACIT Fatigue Scale which is a short, 13-item, that measures an individual’s level of fatigue during their usual daily activities over the past week. A validated Italian version of the Fibromyalgia Impact Questionnaire (FIQ-R) was used to evaluate the level of functional impairment as weel as the FAS index which is a short and easy to complete self-administered index combining a set of questions relating to non-articular pain, fatigue and the quality of sleep that provides a single composite measure of disease activity ranging from 0 to 10. The HBOT protocol comprised 20 sessions, 3 days/week, 90 min, 100% oxygen at 2.5 ATA. Results The effect of the hyperbaric oxygen treatment on the clinical symptoms are summarised in table 1. HBOT treatments of treated group led to statistically significant improvements in the mean scores of pain and fatigue (FACIT) after 10 and 20 HBOT sessions (mean change of pain after 20 sessions −1.76±2.5, p Conclusions These preliminary data show that HBOT may determine a significant clinical improvement in patients affected by FM and resistant to the common pharmacological treatment. However, further studies of large numbers of patients are required in order to confirm this preliminary finding and modify treatment strategies accordingly. Reference [1] Barilaro G, et al. Isr Med Assoc J. 2017;19:429–34. Disclosure of Interest None declared

Background The treat-to-target (T2T) strategy for the management of psoriatic arthritis (PsA) recently proposed by EULAR recommendations suggests to ideally achieve remission/Low Disease Activity (LDA) in all treated patients, but nowadays data on remission/LDA rate in a real-world setting are still lacking. Objectives To evaluate the disease activity state in a real-life cohort of PsA patients treated with synthetic and/or biologic disease modifying drugs (DMARDs). Methods We undertook a cross-sectional analysis of all PsA consecutive patients enrolled in a large Italian multicentric registry including 7 Italian tertiary rheumatology centres. Disease activity defined as number of swollen (SJ) and tender (TJ) joints, Leeds Enthesitis Index (LEI), number of dactylitis, Body Surface Area (BSA), patient global assessment (PGA), patient pain (PP), Health Assessment Questionnaire Disability Index (HAQ-DI), and C-reactive protein (CRP, mg/L) were computed and the rates of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/LDA and Minimal Disease Activity (MDA) were calculated. Subanalysis after stratification according to ongoing treatment (sDMARDs or bDMARDs) were also performed. Results The study population included 362 PsA patients (56.6% men; mean [±standard deviation, SD] age 53.3±12.4 years; mean [±SD] disease duration 9.4±8.2 years), treated with sDMARDs (15.8%, mainly methotrexate [66.6%]) or bDMARDs (79.6%, mainly anti-TNF agents [72.9%], as monotherapy [78.1%] or in combination with sDMARDs [21.9%]). Oligoarthritis (32%), polyarthritis (42%), axial involvement (11.9%), enthesitis (10.5%), and dactilytis (3.6%) were the reported predominant subsets of PsA. In the overall population the mean values [±SD] of disease activity measures were: SJ count 1.4±2.6, TJ count 1.9±3, LEI 0.5±1.1, number of dactylitis 0.1±0.3, BSA 2.6±6.9, PGA 1.4±2.6, PP 3±2.6, HAQ-DI 0.4±0.5, CRP level 3.4±8, and DAPSA 9.3±9.2. The rates of DAPSA LDA and remission were 46.9% and 31.7%, respectively. We found 51.6% of patients achieving MDA, without significant difference according to ongoing treatment (53.4% and 51% in bDMARD versus sDMARD treated patients, respectively; p=0.87). Conclusions In our real-life cross-sectional analysis, an acceptable comprehensive disease control was reported only in half of patients, irrespectively of ongoing therapy. These findings suggest the need to further improve the real-world application of T2T strategy for the management of PsA. Disclosure of Interest None declared

Background It has been demonstrated that miRNAs expressed in PBMCs and salivary glands of patients affected by Sjogren’s Sydrome (SS) could be involved in the epigenetic control of the disease. Objectives We aimed to compare the concentration of miRNA-146a/b, 16, 17–92 cluster and 181a in salivary and plasmatic samples collected from SS patients and healthy controls and to evaluate the associations with clinical, laboratory and ultrasound findings. Methods We collected plasmatic and salivary samples from 28 patients (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years) affected by primitive SS according to ACR 2012 and/or 2016 criteria and 23 matched healthy controls. In the group of patients, the following data were recorded: ESSDAI and ESSPRI scores, anti-SSA and anti-SSB status and laboratory data, Schirmer’s test, ultrasound scores of the four major salivary glands according to Cornec et al. and concomitant treatments. The following miRNA were extracted, retro-transcribed and quantified: miR16–5 p, miR17–5 p, miR18a-5p, miR19a-5p, miR19b-1–5 p, miR20a, miR92–5 p, miR146a-5p, miR146b-5p, miR181a-5p. Results The concentration of miRNAs evaluated in plasma and saliva did not significantly match both in patients and in controls, underlining a different modulation in their expression according to the corporeal district. In patients and controls miRNAs16, 17 and 20 were hyper-expressed and miRNA146b and 181 hypo-expressed in salivary samples compared to plasmatic ones. Salivary miRNAs 18a and 146a were hyper-expressed in patients and hypo-expressed in controls, when compared to plasmatic concentrations. Comparing salivary and plasmatic patients’ miRNAs concentrations to those of healthy subjects, plasmatic miRNA16 and 181a were significantly more expressed in patients than in controls (two-tailed Wilcoxon test and Student’s T test for unpaired samples). In SS patients, salivary miRNA 181 and 146a were significantly increased in older subjects (p=0.01 and p=0.04 respectively). Spearman’s correlation revealed that salivary miRNA146b was significantly hyper-expressed in patients with worse ESSPRI scores (p=0.02); on the contrary, salivary miRNA17, 146b and plasmatic miRNA17 were reduced in patients with higher scores at ultrasound evaluation (p=0.01, p=0.01 and p=0.04 respectively). Plasmatic concentration of miRNA18a was increased in patients with less lachrymal production at Schirmer’s test (p=0.01) and plasmatic concentration of miRNA17 was reduced in patients with higher ESR values (p=0.01). Salivary miRNA18a was significantly increased in patients with anti-La/SSB (p=0.04; Mann-Whitney U test for unpaired samples). Salivary and plasmatic miRNAs did not correlate with disease duration and concomitant therapies. Conclusions Our data show that the expression of salivary miRNAs 17, 18a and 146b may be altered in SS patients and associated with worse ultrasound and ESSPRI scores and anti-La/SSB positivity. Disclosure of Interest None declared

ObjectiveTo define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.MethodsA multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.Results361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.ConclusionsPD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.

Introduction To assess the impact of certolizumab pegol (CZP) treatment on clinical, patient-reported, and musculoskeletal ultrasound outcomes and to determine the treatment response time point most predictive of long-term outcomes in Italian patients with rheumatoid arthritis (RA). Methods CZP-SPEED (NCT01443364) was a 52-week, open-label, prospective, interventional, multicenter study. Biologic-naïve patients with moderate-to-severe active RA, who had failed at least one DMARD treatment, received CZP (400 mg at weeks 0, 2, and 4, then 200 mg every 2 weeks) concomitantly with methotrexate. The primary objective was to identify the time point of clinical response {decrease in 28-joint Disease Activity Score [DAS28(ESR)] ≥ 1.2} most predictive of a clinical response at week 52. Additional clinical and patient-reported outcomes were measured. Power Doppler (PD) ultrasound was used to assess synovial effusion, synovial proliferation, PD signal, cartilage damage, and bone erosion according to international guidelines. Results A total of 132 patients were enrolled and received CZP; 91/132 (69%) completed to week 52. Predicted 52-week responses for early responders (week 2 onwards) were between 65% and 70%. Rapid improvements in joint cavity widening and PD signal were observed to week 8 and maintained to week 52. Cartilage damage and bone erosion were stable over 52 weeks. No new safety signals were identified. Conclusion In Italian CZP-treated patients with moderate-to-severe RA, week 12 clinical responses may be predictive of long-term response at week 52. Rapid improvements in clinical, patient-reported, and musculoskeletal ultrasound outcomes were maintained to week 52. These data may aid rheumatologists to make earlier treatment decisions. Trial Registration ClinicalTrials.gov identifier, NCT01443364. Funding UCB Pharma. Electronic supplementary material The online version of this article (10.1007/s12325-018-0751-8) contains supplementary material, which is available to authorized users.

The role of pericytes in systemic sclerosis (SSc) is unclear because of the difficulty in phenotyping them. They are mainly distributed in the pre-capillary, capillary and post-capillary abluminal side of non-muscular micro-vessels, express platelet-derived growth factor receptors (PDGFRs), and preside over vascular integrity and regeneration. By establishing close contact with many endothelial cells, a single pericyte can regulate ion influx, mechanical stress, leukocyte diapedesis, and platelet activation. Moreover, under pathological conditions such as SSc, pericytes may acquire a contractile phenotype and respond to various stimuli, including endothelin, angiotensin II and reactive oxygen species. The pericytes of SSc patients share some molecular patterns with myofibroblasts or fibroblasts, including A disintegrin and metalloproteinase domain 12 (ADAM-12), α-smooth muscle actin (α-SMA), the extra domain A (ED-A) variant of fibronectin, and Thy-1. Following stimulation with PDGF-β or transforming growth factor-β (TGF-β), pericytes may acquire a myofibroblast phenotype, and produce extracellular matrix or indirectly promote fibroblast activation. They may also contribute to fibrosis by means of epigenetic regulation. The pericyte plasmalemma is particularly rich in caveolae containing caveolin-1, a deficit of which has been associated with defective vessel tone control and lung fibrosis in mice. Consequently, dysfunctional pericytes may underlie the microangiopathy and fibrosis observed in SSc patients. However, given its variability in biological behaviour and the lack of a pan-pericyte marker, the exact role of these cells in SSc warrants further investigation.

Background Tocilizumab (TCZ) is a monoclonal antibody (moAb) directed against the IL-6 receptor approved for moderate-to severe rheumatoid arthritis (RA) treatment. Some authors have reported a beneficial effect of TCZ in preventing lung and subcutaneous nodulosis in RA patients. On the contrary, to our knowledge no data concerning the acceleration of subcutaneous nodulosis under TCZ therapy are currently available. Objectives We report a small case series of 5 RA patients experimenting an evident worsening of subcutaneous nodulosis during the treatment with intravenous tocilizumab. Methods Our cohort included 5 patients (1 male and 4 females, mean age ± Standard Deviation (SD) 64±10.6 years, mean disease duration ± SD 21.8±10.9 years). Four patients were rheumatoid factor and anti-citrullinated peptide antibodies positive. Each patient had been previously treated with several conventional and biologic drugs. At the time of observation, three subjects were practicing methotrexate (MTX), two patients were taking hydroxychloroquine (HCQ) and one patient was taking prednisone. Intravenous tocilizumab 8 mg/kg every 4 weeks was administered for a mean ± SD of 43.4±32.4 months, with a good disease control in 3 cases. All the patients had a previous history of subcutaneous nodulosis that considerably worsened during the treatment with tocilizumab. Patients experimented the development of new subcutaneous nodules localized at the fingers, elbows or the inframammary fold, tending to ulceration. The management of this medical event included the tapering of MTX, the administration of steroids, the addition of HCQ, the use of antibiotics and surgery. However, neither pharmacological nor surgical treatment was completely effective, as nodules tended to recur and to increase in number and dimensions. Results To our knowledge this is the first report describing an accelerated subcutaneous nodulosis in a small cohort of RA patients treated with tocilizumab. Disclosure of Interest None declared

Background Fatigue in fibromyalgia is a very common and disabling symptom, being reported by over 75% of patients. However, the relationship between fatigue and the different manifestations of fibromyalgia has not been convincingly elucidated. Objectives Aim of the our work was to study the relationship between fatigue, pain, and somatic symptoms in fibromyalgia. Methods 123 patients with fibromyalgia classified according to 2010 criteria were studied, 113 Females and 10 Males, mean age 47.41±11.21 years, mean disease duration 6.83±6.52 years. Fatigue was assessed by FACIT-Fatigue questionnaire (13 items, score 0–52, higher values representing less fatigue), and results were correlated to the number of Tender points (TP), to Widespread Pain Index (WPI), to Symptom severity Scale (SSS), and to Polysymptomatic Distress Scale (PDS) values. Correlations were computed by parametric or non parametric methods as appropriate. Results Average FACIT-Fatigue score (22.51±10.6) was lower than the 25th percentile of the general population (35), and was not correlated to age or to disease duration (p>0.05). FACIT-Fatigue showed statistically significant inverse correlations with the number of tender points (r = -.303, p=0.001), WPI score (r=-0.329, p Conclusions The results of our study confirm that fatigue is a prominent feature of fibromyalgia. Higher levels of fatigue reflect higher levels of widespread pain, and a higher burden of somatic symptoms. Disclosure of Interest None declared

Background Several studies have demonstrated that musculoskeletal ultrasound (MSUS) is more sensitive in diagnosing arthritis when compared to clinical examination, although, as underlined in a recent review, still remains controversial whether it can improve substantial discriminatory value in an early arthritis (EA) setting.(1) In 2011 Gutierrez M. et al. published preliminary data on high frequency of peritenon extensor tendon inflammation in Psoriatic arthritis (PsA) patients, suggesting a relevant potential role for US in differential diagnosis between Rheumatoid Arthritis (RA) and PsA at metacarpophalangeal (MCP) joints level and recommending additional research in order to confirm these data.(2) Objectives To compare MSUS findings between early RA and early Spondyloarthritis (SpA) patients at MCP joints level. Methods From a consenting cohort of EA patients presenting to our Rheumatology Department, we retrospectively selected 35 patients that within one year from the first visit had a defined diagnosis of RA (according with the 2010 ACR/EULAR criteria) or of axial/peripheral SpA (according with the 2009 ASAS criteria). Demographic, clinical parameters and MCPs9 MSUS assessment at baseline were recorded during the patients9 first EA clinic visit by an experienced Rheumatologist and by a blinded skilled sonographer. ESAOTE MyLAB 70 with 6–18 MHz linear array transducer was used for all patients scanning and US were scored according with OMERACT guidelines. Results MSUS data of twenty RA patients (17 F – 3 M; median age of 59 yrs with range 35–83 yrs, median time for defined diagnosis of 2,4 months with range 1–11 months) and 15 SpA patients (9F–6M; median age of 53 yrs with range 18–78 yrs, median time for defined diagnosis of 1,7 months with range 1–8 months) were retrospectively analyzed. At the first EA clinic visit, all patients showed at least one joint with synovial fluid and/or synovial hypertrophy in Grey scale (GS) with a score >1 and no statistically significant differences were found in the percentage of patients that presented at least one joint with power Doppler (PD) positivity (55% RA Vs 53% SpA,p=0,92) and that presented PD positivity tenosynovitis of the flexor tendons in at least one finger (10% RA Vs 33% SpA, p=0,08). A statistically significant difference was found in the percentage of patients with erosions in at least one MCP (25% RA Vs 0% SpA, p=0,036) and in the percentage of patients with PD positive paratenonitis of the extensor tendons in at least one finger (30% RA Vs 80% SpA pts, p=0,003). Conclusions Early RA patients showed a statistically higher percentage of erosions at MCPs9 MSUS evaluation of the first visit of the EA clinic, when compared with early SpA group and early SpA patients presented at the level of the extensor tendons an higher percentage of PD positive paratenonitis when compared with the early RA group. References Lage-Hansen PR. et al. The role of ultrasound in diagnosing rheumatoid arthritis, what do we know? An updated review. Rheumatol Int.2017Feb;37(2):179–187. Gutierrez M. et al. Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level.Ann Rheum Dis.2011 Jun;70. Disclosure of Interest None declared

Background There are many evidences that Th9 lymphocytes take part to the pathogenesis of rheumatoid arthritis (RA), however it is unclear whether these cells are implicated in the immunogenicity of biologic agents. Objectives We aimed to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in Th9 percentages following an “in vitro” stimulation test. Methods PBMCs from 55 consecutive RA outpatients (15 drug-free, 20 successfully treated with branded infliximab and 20 failing branded infliximab) and from 10 healthy controls were collected. PBMCs were cultured with/without 50 μg/mL infliximab originator (Remicade®) or 50 μg/mL infliximab biosimilar (Remsima®), 50 μg/mL Human IgG1kappa and 50 μg/mL recombinant Human IgG Fc for 18 hours. Th9 lymphocytes were identified by means of flow cytometry as PU.1+, IRF4+, IL9+ CD4+ cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naive from memory IL-9-producer cells. Results In unstimulated condition, RA patients showed the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentage of PU.1+, IRF4+ Th9 cells, CCR7+, CD45RA- central memory and CCR7-, CD45RA- effector memory IL-9 producer cells significantly increased in the group of infliximab non responder RA patients. On the contrary, no significant variation was observed after biosimilar exposure. Figures 1,2,3,4 resume the results. Conclusions According to our results, Th9 cells seem to be involved in the immune response against the epitopes of branded but not biosimilar infliximab and this condition could rely on the recall and the stimulation of both central and effector memory cells. Further studies are indeed needed to confirm these data. Disclosure of Interest None declared