Safety of belimumab in association with denosumab in a patient affected by Lupus Erythematosus: a case report

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by multisystemic involvement. Owing to multifactorial etiologies, low bone mineral density (BMD) osteoporosis (OP) and fragility fractures (FFx) have been very frequently documented in these patients. Appropriate treatments to minimize underlying immunologic disease activity remain mandatory, and the development of strategies to prevent and treat important complications as osteoporosis is needed.We present the clinical case of a female SLE patient treated simultaneously with belimumab (anti-BLyS) for the underlying disease, and denosumab (anti-RANKL) for concomitant severe osteoporosis. As these monoclonal antibodies have been recently introduced into the market, their combination has not been reported in literature yet. In this case, the combined administration proved a viable option for a SLE patient with osteoporosis and bisphosphonates contraindications

Eosinophilic Pneumonia Associated with Rheumatoid Arthritis: Description of a Case Report and Review of the Literature

Rheumatoid arthritis (RA), a systemic inflammatory disease, may induce pulmonary manifestations. We describe a case of longstanding RA presenting with eosinophilic pneumonia (EP). Rare case reports of tissue eosinophilia involving isolated organs in the setting of RA exist in the literature. It has been shown that the production of proinflammatory cytokines activates different cell group and can simultaneously play a role in RA and induce eosinophils infiltration in target tissue. An appropriate lowest possible dosage of steroid therapy is essential, whereas EP may be a rare subset of pulmonary involvement in RA

Rheumatic Diseases and Biosimilars: Evidence about Switch from Originators to Biosimilars in the Real Life

Biosimilars are broadly available for the treatment of several diseases including inflammatory arthritis. Thanks to biosimilars it has been possible to treat a greater number of rheumatic patients who previously were undertreated due to the high cost of originators, in several countries. There are a lot of data from double blind, randomized, controlled clinical trials, especially on TNF inhibitors (TNFi), 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 mainly for economic reasons. However, despite the considerable saving, such shifts to biosimilar drugs are still being debated, principally over their ethical implications. Since the drugs are similar but not identical, the main issues are related to the possibility to compare the adverse events and/or the lack of efficacy and, to date, the variability in effectiveness for a single patient remains an unpredictable datum before effecting the switch. Despite encouraging data about the maintenance of efficacy and safety after the switch, there are many reports of discontinuation due both lack of efficacy or and adverse events. In this chapter we aim at showing the disease activity trend and the safety after the transition to TNF-i biosimilars in patients with rheumatic diseases in real life.

Influence of safety warnings on the prescribing attitude of JAK 2inhibitors for rheumatoid arthritis in Italy

The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA) and 74 filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US 75 Food & Administration (FDA) raised concerns on the safety of TOFA after its approval. This 76 prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA 77 use then extended in a third warning to all Jaki in patients at high risk of developing serious adverse 78 events (SAE). These included thrombosis, major adverse cardiac events (MACE) and cancer. Thepurpose of this work was to analyze how the first two safety warnings from EMA affected the pre- 80 scribing of Jaki by rheumatologists in Italy. All patients with rheumatoid arthritis who had been 81 prescribed JAKi for the first time in a 36-month period from July 1, 2019, to June 30, 2022 were con- 82 sidered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology 83 centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi 84 prescription had occurred before the EMA's first safety alert (July 1-October 31, 2019, Group 1), 85 between the first and second alerts (November 1, 2019-February 29, 2020, Group 2), or between the 86 second and third alerts (March 1, 2021-June 30, 2021, Group 3). Percentage and absolute changes in 87 patients prescribed the individual JAKi were analyzed. Differences among the three Groups of pa- 88 tients in demographic and clinical characteristics were also assessed. A total of 864 patients were 89 prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 90 in Group 2 and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients 91 prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, 92 there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In 93 the first Group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed 94 by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second Group, the most prescribed JAKi was BARI 95 (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third Group, BARI was still 96 the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%) 97 and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between 98 Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). Patients who were prescribed 99 BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p 100 ˂ 0.01). In contrast, patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). 101 These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi 102 prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers 103 as favorable in terms of risk/benefit ratio and their use gradually increased at the expense of the 104 other molecules

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

Rheumatic manifestations in inflammatory bowel disease

Rheumatic manifestations are the most frequent extra-intestinal manifestations (EIMs) in Inflammatory Bowel Disease (IBD) patients, and they are responsible for a relevant reduction of quality of life. IBD is associated with a variety of musculoskeletal manifestations such as arthritis and non-inflammatory pain as well as with metabolic diseases, such as osteoporosis. Different imaging techniques (primarily ultrasound, magnetic resonance imaging and X-rays) can help the clinician to correctly identify the nature of manifestations and to treat the patient accordingly. Nowadays, in the setting of IBD-related arthritides, different drugs are available and can be effective on both articular and intestinal involvement. Therefore, a multi-disciplinary approach provides an early diagnosis and a better clinical outcome that can only be given from the recognition and consideration of the different EIMs. As for rheumatic manifestations, namely IBDrelated arthritis, an early intervention allows to control disease activity and to prevent structural damage

Cardiovascular Organ Damage in Clinical Subtypes of Systemic Sclerosis: Arterial Stiffness and Echocardiography Might Not Be the Ideal Tools for Patient Risk Stratification

Background. Vascular damage is recognized as a diagnostic landmark in systemic sclerosis (SSc), both in its limited and diffuse subtypes. Early detection at a subclinical stage with transthoracic echocardiography (TTE) and carotid femoral pulse wave velocity (cfPWV) may be helpful in therapeutic planning and management. Aim of the Study. The aim of the study was to evaluate presence of subclinical cardiovascular damage in patients with limited and diffuse SSc in comparison with a cohort of healthy individuals. Methods. Consecutive patients with limited and diffuse SSc underwent complete TTE and cfPWV and a complete review of clinical data. As controls, 23 healthy subjects with similar hemodynamic profiles were selected. Results. 41 patients (35 female, aged 56.9 years), 21 with diffuse and 20 with limited SSc, were recruited. Past medical history, cardiovascular risk factors, gender distribution, and disease duration were similar in the two groups as well as TTE parameters and hemodynamic indexes—cfPWV (6.5 [6–6.8] vs. 7.0 [6.2–8.5], p=0.24) and augmentation index (145.6 ± 14.2 vs. 149 ± 20.6, p=0.52). Patients with limited SSc were 10 years older than patients with diffuse SSc. In the multiple regression analysis, only age (p=0.0154) and disease duration (p=0.0467) resulted as the significant determinant of cfPWV. When compared to healthy controls, no significant difference emerged in TTE or hemodynamic indexes. Conclusion. In SSc, cfPWV increases with age, with no additional impact of pathology or subtype. Vascular damage in the SSc population is not accurately reflected in increased arterial stiffness, as evaluated with cfPWV, or classically defined echocardiographic findings of organ damage (i.e., left ventricular concentric remodelling and increased filling pressures)