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.

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.

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.

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.

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.

Calcinosis in systemic sclerosis: subsets, distribution and complications.

OBJECTIVE: To retrospectively analyse the features of calcinosis in a cohort of SSc patients. METHODS: Charts of SSc patients attending the Ulcer Unit of the Rheumatology Department, University of Florence and presenting a clinical suspicion of calcinosis were considered in the study. Data on clinical history, including recent skin changes, and clinical examination of all areas with suspected calcinosis, radiological imaging of the calcinotic area, demographics and SSc-related organ involvement and pain measured by a visual analogue scale were recorded. RESULTS: In 52 of 112 SSc patients, a total of 316 calcinoses were recorded and were divided into visible and palpable {154 [47.4%], clustered according to their macroscopic features as mousse [49 (31.8%)] and stone [: 105 (68.2%)]} and non-visible but palpable {: 162 [52.6%]: net [5 (3%)], plate [22 (13.8%)] and stone [135 (83.2%)]}. The X-ray-based classification of all calcinoses, both visible and non-visible, was as follows: stone, 289 (91.4%); net, 12 (3.8%) and plate, 15 (4.8%). Skin ulcers complicated 154 of 316 calcinoses (48.7%). Mousse calcinosis was associated with pulmonary arterial hypertension, the stone subset was suggestive of pulmonary involvement and justified further investigation and the net subset was the slowest to heal. CONCLUSION: Our data indicate that calcinosis may be classified in SSc as mousse, stone, net and plate according to its clinical and X-ray features. This classification awaits validation for a possible use in clinical practice and to support early treatment and prevention of complications.

Digital ulcers as a sentinel sign for early internal organ involvement in very early systemic sclerosis.

OBJECTIVE: The aim of this study was to evaluate the presence of digital lesions in very early diagnosis of SSc (VEDOSS) patients and its possible association with internal organ involvement. METHODS: One hundred and ten VEDOSS patients were investigated for the presence of digital ulcers (DUs), digital pitting scars, calcinosis, necrosis or gangrene, nailfold videocapillaroscopic abnormalities, disease-specific autoantibodies (ACA and anti-topo I) and internal organ involvement. RESULTS: Four patients reported a history of digital pitting scars, while 25 patients presented an active DU or reported a history of DUs. In particular, 16 patients presented with active DUs (14/16 also reporting a history of previous DUs), while the other 9 patients reported a history of DUs only. A statistically significant association between DUs and oesophageal manometry alteration was found in the whole DU population, as well as in the history of DU and the presence of active DU with/without a history of DU subgroups (P < 0.01, P = 0.01 and P < 0.05, respectively). DUs were observed in VEDOSS patients with internal organ involvement but not in those without organ involvement. CONCLUSION: DUs are already present in VEDOSS patients characterized by internal organ involvement, significantly correlating and associating with gastrointestinal involvement. DUs may be a sentinel sign for early organ involvement in VEDOSS patients.

Efficacy and Safety of Filgotinib in Rheumatoid Arthritis Patients Aged over and under 65 Years (ENANTIA-65).

BACKGROUND: According to recent data, the age of patients could represent an important risk factor for MACE (major cardiovascular events), cancer, and VTE (venous thromboembolism) during treatment with JAK inhibitors in rheumatoid arthritis. We decided to analyze the population involved in the ReLiFiRa study by identifying two groups of patients: 65 years or more and less than 65 years of age, evaluating the efficacy and tolerability of 200 mg of Filgotinib daily. METHODS: Of the 120 ReLiFiRa patients, 54 were younger than 65 years old and 66 patients were 65 years old or older. The data of efficacy and tolerability of treatment with FIL 200 mg daily for 6 months were evaluated. RESULTS: After six months of treatment, FIL was effective in both age groups. In both groups, the median values of steroid DAS28, CDAI, ERS, PCR, tender joints, swollen joints, VAS, HAQ, PGA patients, and PGA physicians were reduced with a statistically significant difference comparing these values with the baseline values. The difference in age did not impact the effectiveness of the drug. The lipid profile data also did not demonstrate significant differences between the two age groups; however, the comparison between younger vs. older patients' populations regarding the total cholesterol/HDL ratio and LDL/HDL ratio shows a statistically significant difference: total cholesterol/HDL 3.4 (2.12-3.66) vs. 3.64 (3.36-4.13) p = 0.0004, LDL/HDL 1.9 (0.98-2.25) vs. 2.41 (2.04-2.73) p = 0.0002. There are no differences regarding the atherogenic index (LDL-C/HDL-C) and coronary risk index (TC/HDL-C) compared to baseline. CONCLUSIONS: After six months of treatment with FIL, the older population group showed a higher level of LDL and a lower level of HDL compared to younger patients. The atherogenic index and coronary risk index are higher in patients aged ≥ 65 years, but interestingly, there were no differences when comparing the 6-month data to baseline values. This condition highlights the impact of typical risk factors that act independently of treatment with Filgotinib.

Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study.

OBJECTIVE: To evaluate the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy. METHODS: 20 patients with SSc with refractory polyarthritis and seven with refractory myopathy from the EUSTAR (EULAR Scleroderma Trials and Research) network were included: 15 patients received tocilizumab and 12 patients abatacept. All patients with SSc-myopathy received abatacept. Clinical and biological assessments were made at the start of treatment and at the last infusion. RESULTS: After 5 months, tocilizumab induced a significant improvement in the 28-joint count Disease Activity Score and its components, with 10/15 patients achieving a EULAR good response. Treatment was stopped in two patients because of inefficacy. After 11 months' treatment of patients with abatacept, joint parameters improved significantly, with 6/11 patients fulfilling EULAR good-response criteria. Abatacept did not improve muscle outcome measures in SSc-myopathy. No significant change was seen for skin or lung fibrosis in the different groups. Both treatments were well tolerated. CONCLUSIONS: In this observational study, tocilizumab and abatacept appeared to be safe and effective on joints, in patients with refractory SSc. No trend for any change of fibrotic lesions was seen but this may relate to the exposure time and inclusion criteria. Larger studies with longer follow-up are warranted to further determine the safety and effectiveness of these drugs in SSc.

Ultrasound detects occult entheseal involvement in early psoriatic arthritis independently of clinical features and psoriasis severity.

OBJECTIVES: Entheseal involvement is a frequent and distinctive feature of psoriatic arthritis (PsA), and is often under-diagnosed. The aim of the present study is to investigate using ultrasound (US), lower limb entheseal abnormalities in patients with early psoriatic arthritis (ePsA) and to evaluate their correlation with ePsA clinical characteristics. METHODS: Ninety-two ePsA patients (with duration of symptoms less than 1 year), diagnosed according to CASPAR criteria, were consecutively scored with Glasgow Ultrasound Enthesitis Scoring System (GUESS) and Power Doppler (PD) US (My Lab 70 Esaote) of lower limbs entheses (quadriceps, patellar, achilles tendons and plantar fascia). Patients were clinically examined by palpation of lower limbs entheses, Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) and total Psoriasis Area and Severity Index (PASI). Correlations were investigated between GUESS and PD with other ePsA clinical characteristics (duration of symptoms and morning stiffness, pain and fatigue visual analogue scale [VAS], Health Assessment Questionnaire SpA-modified [S-HAQ]). RESULTS: All patients had GUESS>1 and 40.2% showed positive PD signal on entheses, at a higher percentage than tenderness revealed by clinical examination (29.3%). GUESS and PD did not correlate with MASES, PASI and other clinical characteristics. No significant differences in GUESS and PD were detected between positive or negative findings of MASES and PASI. CONCLUSIONS: US detects subclinical entheseal involvement in ePsA, independently of ePsA clinical examination and symptoms.

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.

CCL2, CCL3 and CCL5 chemokines in systemic sclerosis: the correlation with SSc clinical features and the effect of prostaglandin E1 treatment.

OBJECTIVES: Chemokines favour leukocyte homing and participate actively in inflammation and accumulation of extracellular matrix. The aim of our work is to assess in patients with systemic sclerosis (SSc) the serum levels of CC chemokines: CCL2 monocyte chemotactic protein-1 (MCP-1/CCL2), CCL5 'regulated upon activation, normal T expressed and secreted' (RANTES/CCL5) and CCL3 'macrophage inflammatory protein 1 α' (MIP1α/CCL3), their associations with clinical characteristics and modulation by infusions of the prostaglandin E1 (PGE1) analogue, alprostadil alpha-cyclodextrin. METHODS: Serum levels of MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 were studied by ELISA in 40 patients with SSc (34 lSSc, 6 dSSc) before and after 3 consecutive daily PGE1 infusions (60 µg) and compared to 30 healthy controls. We recorded clinical (age, duration of disease, ulcers, teleangectasias, calcinosis, skin score [mRSS], capillaroscopy pattern, heart and lung involvement) and immunological characteristics (ANA/ACA/Scl70) of patients. RESULTS: MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 levels were significantly higher in SSc patients than in controls and significantly decreased after PGE1 treatment. MCP-1 levels, higher in dSSc and Scl 70 positive patients, correlated with mRSS. CONCLUSIONS: The high levels of circulating chemokines might support a role of MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 in SSc pathogenesis and the correlation of MCP-1 with the extent of skin fibrosis might imply its involvement in the development of fibrosis in SSc. PGE1 down-regulates serum MCP1/CCL2 and RANTES/CCL5 levels, suggesting its possible additional effect on inflammation and cell trafficking in SSc.

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.

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.

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.

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.

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.

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.