ReLiFiRa (Real Life Filgotinib in Rheumatoid Arthritis): Retrospective Study of Efficacy and Safety in Common Clinical Practice.

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time. CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

Persistence of remission after lengthening of golimumab in inflammatory joint diseases.

OBJECTIVES: In refractory inflammatory joint diseases (IJDs) biological disease-modifying anti-rheumatic drugs (bDMARDs) may achieve remission. EULAR recommends bDMARD tapering when remission persists. However, guidelines on tapering modalities and criteria for patient selection are lacking. We aimed to evaluate remission persistency after lengthening the time between injections of golimumab in patients affected by IJD and to identify any patient or disease characteristics associated to flare after lengthening. METHODS: Patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) treated with golimumab were enrolled in a retrospective observational study. Demographic data, ESR, cRP, DAS28/ BASDAI, were collected at baseline and during the follow-up (T1- defined as a medical check-up after 1 year of treatment or, for patients with longerg exposure, the first medical check-up in 2016, when at our unit we began to experience drug tapering- and T2- 12 months after the lengthening was started). In 22/80 patients in remission at T1, injection time was lengthened. RESULTS: Eighty patients were enrolled, 34 AS, 33 PsA, 9RA and 4 JIA. At baseline, all had an active disease. At T1, 60/80 patients reached remission and 22/60 patients started tapering. At T2, 20/22 pts (91%) were in remission. At T1 BASDAI was higher (2.2, SD 0.28 vs. 0.58, SD 0.47; p<0.001) in patients who lost remission at T2.Patients who flared recovered remission once taken back to a 28-day interval. 4/38 patients maintained at the standard dose flared up and switched/swapped bDMARD. The difference in retention rate toward patients on reduced dose was not significant. CONCLUSIONS: Results show that golimumab lengthening is safe and successfully maintains remission. In patients who experienced a flare after lengthening, the standard regimen promptly restored remission.

Management of intrathoracic phosphaturic mesenchymal tumor by nonintubated uniportal video-assisted thoracic surgery in a fragile patient.

BACKGROUND: Phosphaturic mesenchymal tumors are rare neoplasms, frequently presenting with osteomalacia. These neoplasms usually grow at a slow rate and are associated with unspecific symptoms. CASE: In this study, we present the case of a 70-year-old woman who had been suffering from musculoskeletal pain, hypophosphatemia, and spontaneous fractures. Positron emission tomography with Gallium showed increase uptake in a subpleural lesion. CONCLUSION: The patient underwent surgical excision of the subpleural lesion with a non-intubated uniportal video-assisted thoracoscopic surgery approach.

The positive side of the coin: Sars-Cov-2 pandemic has taught us how much Telemedicine is useful as standard of care procedure in real life.

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.

Intravenous immunoglobulins reduce skin thickness in systemic sclerosis: evidence from Systematic Literature Review and from real life experience.

INTRODUCTION: Intravenous immunoglobulins (IVIG) are a new therapeutic approach in systemic sclerosis SSc. An immunomodulatory and antifibrotic activity has been postulated. IVIG are generally well tolerated and have only rare side effects. Our retrospective study focused its attention on SSc, an autoimmune connective tissue disease, characterized by several complications which has a significant impact on patient's quality of life. The pathophysiology comprises fibrotic, vascular and immunological aspects. AIM: The aim of this study was to verify the effectiveness of IVIG on SSc skin involvement. Moreover, a systematic review of the literature (SLR) of the results obtained to date on the use of Intravenous immunoglobulin (IVIG) in SSc has been also performed. PATIENTS AND METHODS: The data of 24 patients (21 women, 3 male) with refractory diffuse SSc skin involvement were evaluated (mean age was 52.13 years). IVIG infusion at a dosage of 2 g/Kg body weight for 4 consecutive days/month, was started between 2002 and 2019. Skin involvement was evaluated with the modified Rodnan Skin Score (mRSS) before therapy and then again after 6 and 12 months. To perform the SLR, the PubMed, Medline, Embase, and Web of Science database were searched from 1990 to 2020 (keywords: IVIG, systemic sclerosis). Three assessors (E.A., C.B. & M.M.C) identified the criteria to scan all papers. RESULTS: From the total SLR (106 results), 17 papers were identified after the separation of the clinical cases from the studies (total number of treated patients 183). The studies were classified according to the organ involvement considered in each study, as well as the prescribed dose (high or low doses), and the therapeutic regimens. In the selected papers, the organs mainly involved were the skin, the gastrointestinal, the joint and the cardiovascular systems. Only in one case, plasmapheresis was associated to IVIG. All papers reported significant reduction of the skin involvement, although generally the strength of the works was limited the lack of control cases or by the low number of patients involved. From the real life experience, a statistically significant reduction of mRSS was obtained at 6 months follow-up (average value of -6.61 ± 5.2, p < 0.001), and it was further maintained with a significant stabilization after 12-months (-11.45 ± 9.63, p < 0.002). DISCUSSION: This SLR and the data of the retrospective study suggest that IVIG may improve skin involvement reducing mRSS in particular in those patients that were refractory to other standard of care therapies and represents a therapeutic option in patients with concomitant myositis. The literature review revealed encouraging perspectives on the use of this therapy, given the effectiveness found in the selected works.

Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience.

BACKGROUND: Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments. METHODS: Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months. RESULTS: In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months. CONCLUSION: The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.

EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies.

OBJECTIVES: aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). METHODS: Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. RESULTS: EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-ß2-glycoprotein I (ß2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-ß2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-ß2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-ß2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. CONCLUSION: EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

Efficacy and safety of switching from reference adalimumab to SB5 in a real-life cohort of inflammatory rheumatic joint diseases.

OBJECTIVE: SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients. METHOD: Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching. RESULTS: Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5. CONCLUSIONS: Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5.

Combination of denosumab and biologic DMARDs in inflammatory muscle-skeletal diseases and connective tissue diseases.

OBJECTIVE: Osteoporosis (OP) can complicate the course of rheumatic musculoskeletal diseases (RMDs) and connective tissue diseases (CTDs). Denosumab, a monoclonal antibody against RANK-L, showed beneficial effect in rheumatoid arthritis in inhibiting radiographic progression and erosive burden. We tested the efficacy, safety, and persistence on the treatment of the combination of biologic disease-modifying antirheumatic drugs (bDMARDs)/denosumab versus bDMARD in patients with RMD and CTD. METHODS: This is a retrospective evaluation of a single center, including patients with RMD/CTD (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, and overlap syndromes) treatment with bDMARD/denosumab, compared to age, gender, disease, bDMARD, and conventional synthetic disease-modifying antirheumatic drugs-matched controls. RESULTS: Twenty-eight bDMARD/denosumab patients and 49 bDMARD patients were eligible. Despite a statistically significant difference during the first-year efficacy (due to the different baseline timepoint), there was no difference in the efficacy profile in the second year of treatment and in the safety profile (including local, systemic, and serious adverse events). Moreover, no statistically significant difference in the persistence of bDMARD treatment over 2 years of evaluation was found. The combination of bDMARD and denosumab was not an independent predictor of disease flare or bDMARD treatment withdrawal. CONCLUSION: The combination of bDMARD and denosumab does not alter the efficacy and the safety profile of the bDMARD in patients with RMD/CTD. Future studies verifying the radiological disease inhibition could support denosumab use in RMD/CTD other than rheumatoid arthritis, when complicated by OP.

Switching from originator adalimumab to biosimilar SB5 in a rheumatology cohort: persistence on treatment, predictors of drug interruption and safety analysis.

AIMS: Medical and non-medical switching strategies have been adopted in Europe in the last few years. We aimed to investigate persistence on treatment with a SB5 Adalimumab (SB5) biosimilar after switching from Adalimumab (ADA) originator among patients with inflammatory rheumatic musculoskeletal diseases (iRMD), identifying possible predictors of drug interruption and describing adverse events. METHOD: iRMD patients previously switched to SB5 after at least 6 months of ADA were enrolled. Data on concomitant medications, disease flares, and persistence on SB5 up to the last available follow up were collected retrospectively. Kaplan-Meier and Cox regression models were used. RESULT: A total of 172 patients (106 females, ADA duration 5.8 ± 3.8 years) were enrolled, including 34 rheumatoid arthritis, 59 psoriatic arthritis, and 61 axial spondyloarthritis patients. In a 10 ± 3 months follow up, 65 (37.8%) patients presented with adverse events, with 46 (26.7%) showing a clinically defined disease flare (no disease activity and patient reported outcomes assessment were available); 24 patients interrupted SB5 permanently (among them, 11 back-switched to ADA and 8 were prescribed a different biological therapy). Probability of persistence on SB5 was 94.7% at 6 months and 85.1% at 12 months. Baseline corticosteroid [hazard ratio (HR) 3.209, 95% confidence interval (CI) 1.193-8.635, p = 0.021] and therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) (HR 2.876, 95% CI 1.229-6.727, p = 0.015), as well as the baseline corticosteroid dose (HR 1.200, 95%CI 1.026-1.403, p = 0.022) were predictors of drug interruption. CONCLUSION: Our data on persistence of treatment and adverse events are in line with previous reports. Further large cohort studies may confirm baseline corticosteroid and NSAIDs use as predictors of SB5 interruption, helping to identify patients at higher risk of failure after switching.

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus.

OBJECTIVES: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. METHODS: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. RESULTS: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). CONCLUSION: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

The switch from etanercept originator to SB4: data from a real-life experience on tolerability and persistence on treatment in joint inflammatory diseases.

AIMS: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. METHODS: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. RESULTS: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7-15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. CONCLUSION: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.

Effect of Dysmetabolisms and Comorbidities on the Efficacy and Safety of Biological Therapy in Chronic Inflammatory Joint Diseases.

In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M (p = 0.0402) and at LoT (p = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia p = 0.0007; SAH p = 0.0319) with a longer bDMARD retention as well (dyslipidemia p < 0.0001; SAH p < 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients (p = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions (p = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients (p = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.

Risk of Malignancy and Biologic Therapy in Rheumatic Inflammatory Diseases: A Single-center Experience.

Objectives: Biologic disease modifying anti-rheumatic drugs (bDMARDs) have significantly improved the care of patients with rheumatic muscle-skeletal disorders (RMDs). Considering their immunosuppressive action, a theoretical increase of malignancy risk has been a major concern in the last few decades. The objective of this study is to analyze the incidence of malignancies in a cohort of patients affected by rheumatoid arthritis (RA), psoriathic arthritis (PsA), and ankylosing spondylitis (AS) treated with bDMARDs. Methods: The charts of bDMARD-treated RMD patients were reviewed, and data about bDMARD exposure and malignant cancers (excluding non-melanoma skin cancer) were collected. Results: 921 patients were included (median age: 50.59 years, 66.67% females); 1374 bDMARD treatments were administered, 87.12% were tumor necrosis factor inhibitors. A total of 21 malignant neoplasms were detected in 21 patients (61.90% females, median age at cancer diagnosis: 64.99 years), 66.67% in RA patients, 19.05% in PsA, and 14.28% in AS. Among them, 10 patients (47.62%) were treated with etanercept, 6 patients (28.57%) with adalimumab, and 1 case each with tocilizumab, certolizumab, golimumab, infliximab, and abatacept. The most common malignancies that we found were lung cancers, ductal mammary carcinomas, melanomas, and lymphomas. The incidence rate (IR) of malignancies in our cohort was 3.47 per 1000 person-years (p-y); the higher IRs were in RA patients (5.13 per 1000 p-y), in males (4.21 per 1000 p-y), and in patients aged >70 years (10.14 per 1000 p-y). Conclusions: The results of our study showed IR of malignancies in RMD patients treated with bDMARDs that is in agreement with literature data.

The challenge of pet therapy in systemic sclerosis: evidence for an impact on pain, anxiety, neuroticism and social interaction.

OBJECTIVES: The aim of our study was to evaluate the effect of animal-assisted intervention (AAI), a complementary support to traditional therapies focused on the interaction between animals and human beings, in improving psychological trait, anxiety and pain in a cohort of systemic sclerosis (SSc) patients. METHODS: 42 SSc patients, undergoing iloprost intravenous infusion, were divided in three groups: 1) 14 patients submitted to 20 AAI sessions; 2) 14 patients engaged in alternative social activity (control group 1 - C1); and 3) 14 patients without any alternative activity (control group 2 - C2). All patients underwent Visual Analog Scale (VAS), the State-anxiety (STAI-S) and emotional faces at the beginning (s0) and at the end (s1) of each single session, while General Anxiety State-Trait Anxiety Inventory (STAI-T), Beck Depression Inventory (BDI), Social Interaction Anxiety Scale (SIAS), Eysenck Personality Questionnaire-Revised (EPQ-R), the Social Phobia Scale (SPS), the Toronto Alexythymia Scale (TAS-20), the Thought Control Questionnaire (TCQ) were administered at baseline (t0) and at the end of the project (t1). RESULTS: AAI group showed a significant decrease of the anxiety state level in respect to the two control groups (p<0.001). VAS scale resulted lower both in AAI (p < 0.001) and C1 group (p<0.01). Moreover, STAI-T and TAS scores were significantly reduced in AAI group (p<0.001). TCQ scale showed that patients treated with AAI, compared to control group C2, had greater capacity to avoid unpleasant and unwanted thoughts (p<0.05). In AAI group, the EPQ-R test revealed an enhancement of extroversion trait compared to both control groups (p<0.05). CONCLUSIONS: Our data show that AAI significantly reduces pain perception, anxiety, neuroticism and ameliorates patients' social interaction, therefore it may be a useful to allow a better compliance to traditional therapies.

Sirukumab for the treatment of rheumatoid arthritis: update on sirukumab, 2018.

INTRODUCTION: Interleukin-6 (IL-6) is well-known for its pro-inflammatory properties, has been proven to target a wide range of cells in the joint, and has been implicated in extra-articular and articular manifestations in rheumatoid arthritis (RA). Tocilizumab (TCZ) is now widely used in patients with active RA and a number of additional agents that target the IL-6 pathways are under development, including sirukumab (SRK). Areas covered: SRK is an IgG1κ human anti-IL-6 monoclonal antibody which binds to IL-6 and prevents IL-6-mediated downstream effects. Initial trial results in phase-III studies in patients with RA seemed promising, showing improved results in patients with moderate-to-severe RA. Data derive from the phase-II study and the various SIRROUND studies (phase III). Expert commentary: The available data show that SRK50 mg every 4 weeks or 100 mg every 2 weeks will be effective in treating the RA population, with clinical improvements as early as week 2 and sustained over time. The adverse-event profile seems to be similar to TCZ, except for an increased mortality post open-label studies due to infections and cardiovascular events, our knowledge of which will be deepened with post-marketing surveillance and registry data.

Calcinosis in poly-dermatomyositis: clinical and laboratory predictors and treatment options.

OBJECTIVES: We aimed to identify the possible clinical and laboratory predictors of calcinosis in a cohort of patients with a diagnosis of polymyositis (PM) and dermatomyositis (DM). METHODS: We carried out a retrospective analysis of a cohort of myositis patients attending our clinic between January 2013 and May 2014. RESULTS: 74 patients (58 females, 16 males) with PM (30 cases), DM (30 cases), overlap syndrome (13 cases) and inclusion body myositis (1 case) were enrolled. Sixteen patients (21.6%) had calcinosis that occurred a mean of 43.7 months after diagnosis of PDM. At multivariate analysis, patients with calcinosis experienced longer follow-up duration (p=0.006), anti-PM/Scl (p=0.033) and anti-NXP2 (p=0.024) positivity compared to patients without calcinosis. Furthermore, anti-NXP-2 positive C+ showed a diffuse form of calcinosis from the beginning and lower frequency of respiratory tract involvement. No single drug or associations of drugs was found effective in the treatment of calcinosis. CONCLUSIONS: A longer follow-up period of time, DM diagnosis and positivity for PM/Scl and NXP-2 could all be considered risk factors which foresee the development of calcinosis. Moreover, the positivity for antibodies to NXP-2 depicts a distinct phenotype of calcinosis with an early onset and quick widespread dissemination.

Lidocaine controls pain and allows safe wound bed preparation and debridement of digital ulcers in systemic sclerosis: a retrospective study.

In Systemic Sclerosis (SSc), digital ulcers (DU) are painful, difficult to heal, and frequently infected. To reduce the risk of bacterial infection and to prevent chronicity, it is essential to carefully remove necrotic tissue from DU, with maximum patient comfort. Debridement, although very efficacious, is invasive and causes local pain: lidocaine is a local anesthetic commonly used as to fight pain during debridement procedures. The aim of the study was to evaluate the efficacy of lidocaine 4 % in pain control during debridement procedure of DU in SSc. One hundred eight DU characterized by pain Numeric Rating Scale (NRS) >3/10 before starting the procedure were treated with lidocaine 4 % (lidocaine cloridrate 200 mg in 5 ml of injecting solution). Pain was measured with NRS (0-10) before starting debridement, after 15 min of lidocaine application and at the end of the procedure. In DU, in respect to baseline (mean NRS 6.74 ± 2.96), pain after application of lidocaine 4 % for 15 min was significantly lower (mean NRS 2.83 ± 2.73) (p < 0.001). At the end of the procedure, pain control was still maintained and significantly lower (mean NRS 2.88 ± 2.65) in respect to baseline (p < 0.001). No systemic adverse event due to topical lidocaine were observed. In SSc, topical application of lidocaine 4 % significantly reduces pain, allowing a safe debridement procedure, thus improving the management of DU.