Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

BACKGROUND: We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. METHODS: RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. RESULTS: Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. CONCLUSION: Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study.

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Autoantibodies and Rheumatologic Manifestations in Hepatitis C Virus Infection.

HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45-70%), antinuclear (10-40%) and anticardiolipin (15-20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis.

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. METHODS: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1ß, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-ß) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. RESULTS: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-ß, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1ß, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.

Abatacept and granulocyte-colony stimulating factor in a patient with rheumatoid arthritis and neutropenia.

Neutropenia in patients with inflammatory diseases increases the risk of infection due to the disease itself and the related immunosuppressive treatments. We report the case of a 54-year-old female with rheumatoid arthritis and following development of chronic neutropenia. All investigations excluded pathogenic relations with drugs and/or other clinical situations; the gravity of neutropenia required a treatment with G-CSF and the increased articular inflammatory activity justified a biologic-therapy, abatacept (CTLA4 inhibitors). The juxtaposition of immunostimulants and immunosuppressors led to great effectiveness for both hematological and rheumatic issues. To date, while some biologic drugs (TNF, IL6R and CD20 inhibitors) have reported relations with neutropenia, no such relevance subsists for Abatacept. Our case reports the experience of the safe effective use of abatacept and G-CSF for 8 years.