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Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR , and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan-Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024 . Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest.

Introduction: The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program., Methods: PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability., Results: Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate., Conclusion: The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cafaro, Foca, Nanni, Chiumente, Coppola, Baldo, Orzetti, Enrico, Ladisa, Lerose, Nardulli, Maiolino, Gradellini, Gasbarro, Carrucciu, Provasi, Cappelletto, Pasqualini, Vecchia, Veraldi, De Francesco, Crinò, Delmonte and Masini.)

Objective: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study., Methods: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated., Results: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94-1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66-1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56-1.23]). None of the differences were significant., Conclusion: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19., (© 2020, American College of Rheumatology.)

Objective There is dearth of data regarding the outcomes of coronavirus disease 2019 (COVID-19) among rheumatic and musculoskeletal disease (RMD) patients from Southeast Asia. We report the clinicodemographic profile and identify predictors of COVID-19 outcomes in a large cohort of Indian RMD patients. Methods This prospective cohort study, carried out at the Postgraduate Institute of Medical Education and Research, Chandigarh (a tertiary care centre in India), included RMD patients affected with COVID-19 between April 2020 and October 2021. Demographic and clinical and laboratory details of COVID-19 and underlying RMD were noted. Predictors of mortality, hospitalization and severe COVID-19 were identified using stepwise multivariable logistic regression. Results A total of 64 severe acute respiratory syndrome coronavirus-2-infected RMD patients [age 41.5 (19–85) years; 46 (72%) females] were included. Eighteen (28%) patients had severe COVID-19. Twenty-three (36%) required respiratory support [11 (17%) required mechanical ventilation]. Thirty-six (56%) patients required hospitalization [median duration of stay 10 (1–42) days]; 17 (27%) required intensive care unit admission. Presence of co-morbidities [odds ratio (OR) = 4.5 (95% CI: 1.4, 14.7)] was found to be an independent predictor of COVID-19 severity. Co-morbidities [OR = 10.7 (95% CI: 2.5, 45.4)] and underlying lupus [OR = 7.0 (95% CI: 1.2, 40.8)] were independently associated with COVID-19 hospitalization. Ongoing rheumatic disease activity [OR = 6.8 (95% CI: 1.3, 35.4)] and underlying diagnosis of lupus [OR = 7.1 (95% CI: 1.2, 42.4)] and SSc [OR = 9.5 (95% CI: 1.5, 61.8)] were found to be strong independent predictors of mortality. Age, sex, underlying RMD-associated interstitial lung disease and choice of immunosuppressive therapy were not associated with COVID-19 severity or adverse outcomes. Conclusion The presence of co-morbidities was independently associated with COVID-19 severity and hospitalization. Ongoing rheumatic disease activity and the presence of lupus or SSc independently predicted mortality. Age, sex, type of immunosuppressive therapy and presence of RMD-associated interstitial lung disease did not affect COVID-19 severity or outcomes in Indian RMD patients. [ABSTRACT FROM AUTHOR]

Aim: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may have a more severe course in patients with underlying disease or who have had immunosuppression. In this study, it was aimed to determine the frequency of coronavirus disease 2019 (COVID-19) and the mortality rates related to COVID-19 among patients with rheumatic disease., Methods: The patients who were followed up with rheumatic disease in the rheumatology outpatient clinic in a tertiary hospital were retrospectively assessed if they had COVID-19 infection or not between March 2020 and January 2022., Results: A total of 10 682 patients were evaluated. There were 2928 (27.4%) COVID-19-positive and 7754 (72.6%) COVID-19-negative patients. The mean age of COVID-19-positive patients was 46.2 ± 14.6 years, and 65.8% were female. Forty-two (1.4%) patients died due to COVID-19. Among COVID-19-negative patients, 192 patients died. The most common rheumatic disease among patients with COVID-19 was spondyloarthritis (SpA) (30.4%). Corticosteroids were the most common treatment agent in COVID-19-positive patients regardless of mortality. Thirty-one (73.8%) patients were receiving corticosteroids, and 35 (83.3%) patients were receiving immunosuppressive agents among patients with mortality. According to the logistic regression analysis, older age, male gender, and receiving corticosteroid, hydroxychloroquine, mycophenolate mofetil, tofacitinib, rituximab, and cyclophosphamide were found to be related to increased mortality., Conclusion: COVID-19 is a serious infection and the current study emphasized that patients with rheumatic diseases had increased mortality rates, particularly in patients who were old, male, and on immunosuppressive treatments., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: The relative risk of SARS–CoV‐2 infection and COVID‐19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS–CoV‐2 infection in those with RMDs and describe clinical outcomes of COVID‐19 in these patients. Methods: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS–CoV‐2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID‐19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle‐Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel‐Haenszel formula with random effects models. Results: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta‐analyses, we identified an increased prevalence of SARS–CoV‐2 infection in patients with an RMD (RR 1.53 [95% CI 1.16–2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08–2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID‐19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. Conclusion: Patients with RMDs have higher rates of SARS–CoV‐2 infection and an increased mortality rate. [ABSTRACT FROM AUTHOR]

Purpose of Review: To summarize current knowledge of the impact of coronavirus disease 19 (COVID-19) on patients with systemic lupus erythematosus (SLE). Recent Findings: Several observational studies, including case series, patient surveys, and patient registries, have examined the incidence and severity of COVID-19 in patients with SLE. Due to methodologic limitations (focus on sicker patients, exclusion of asymptomatic or mild cases, limited or inaccurate viral testing), it is difficult to determine the risk and outcomes of COVID-19 in SLE patients. Corticosteroids might be associated with increased hospitalizations from COVID-19 in individuals with autoimmune rheumatic diseases. Some immune suppressive treatments do not appear to significantly increase the risk of contracting COVID-19 or poor subsequent outcomes; however, data on the safety of specific drugs remain scarce. Studies in non-autoimmune cohorts have shown more severe COVID-19 in ethnic and racial minorities, populations also more heavily impacted by SLE. Such results have been attributed to highly prevalent socioeconomic disparities and comorbidities. The complex interplay between SARS-CoV-2 and the host immunologic milieu may have particular implications for patients with SLE that remain to be explored. Concerns have been raised of COVID-19 heightening the risk of thromboembolic events in the presence of an SLE-induced procoagulant state. Summary: Limitations in epidemiologic data available to date do not allow for assessing the risk and severity of COVID-19 in patients with SLE. Other than corticosteroids, prior use of some immune suppressive medications does not appear to increase the risk for infection with SARS-CoV-2 however, more comprehensive studies are needed. [ABSTRACT FROM AUTHOR]