The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.

Objective: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients. Method: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59±12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire. Results: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p< 0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000). Conclusion: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19- related mortality was recorded in only SSc patients’ subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients’ population.

The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001). An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients’ population.

Background: Janus kinase inhibitors (JAKis) are a novel class of drugs interfering with intracellular signaling of type I and type II cytokines, which play a crucial role in immune dysregulation associated with several chronic inflammatory diseases. Filgotinib (FIL), in particular, is the newest member of the JAKi class and exerts its therapeutic effects by selectively targeting and inhibiting the kinase activity of JAK1. While the efficacy of FIL in rheumatoid arthritis (RA) has been confirmed in clinical trials, real-world evidence may provide better insights into its effectiveness and safety in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of FIL in adult patients with RA. Demographic information, disease characteristics, prior treatment history, and comorbid conditions were retrieved from clinical records at baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of whom 39 (47.6%) were older than 65 years. The average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers, and 4 patients (4.9%) had a history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1–6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure (n = 3) or adverse events (n = 4). Significant reductions in pain and number of tender and swollen joints were observed at M3 and M6. A relevant proportion of patients achieved DAS28-CRP remission at M3 and M6 (46.3% and 66.2%, respectively). Conclusions: Our data provide additional insight into the effectiveness of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.

Background: In the aftermath of the ORAL Surveillance trial, real-world studies are needed to elucidate the effectiveness and safety of Janus kinase inhibitors (JAKis) in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of filgotinib, a novel JAK1 inhibitor, in adult patients with rheumatoid arthritis (RA). Demographic information, disease characteristics, prior treatment history, and comorbid conditions, were retrieved from clinical records at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of which 39 (47.6%) were older than 65 years. Average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers and 4 patients (4.9%) had a past history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1–6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure (n = 3) or adverse events (n = 4). Significant reductions in pain and number of tender and swollen joints were observed at T3 and T6. A relevant proportion of patients achieved DAS28-CRP remission at T3 and T6 (46.3% and 66.2%, respectively). Conclusion: Our data provide additional insight into the effectiveness and safety of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.