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Importance: The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis). Although international cohort studies have compared cancer outcomes between TNFis, non-TNFi drugs, and Janus kinase inhibitor (JAKis), their generalizability to US patients with RA is limited., Objective: To assess the comparative safety of TNFis, non-TNFi drugs, and JAKis among US patients with RA (ie, the cancer risk associated with the use of these drugs among these patients)., Design, Setting, and Participants: This retrospective cohort study used US administrative claims data from Merative Marketscan Research Databases from November 1, 2012, to December 31, 2021. Follow-up occurred up to 2 years after initiation of biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). Participants included individuals aged 18 to 64 years with RA, identified using at least 2 RA International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes on or before the date of TNFi, non-TNFi, or JAKi initiation ("index date"). Statistical analysis took place from June 2022 to September 2024., Exposures: New initiations of TNFis, abatacept, interleukin 6 inhibitors (IL-6is), rituximab, or JAKis. Individuals could contribute person-time to more than 1 treatment exposure if treatment escalation mimicked typical clinical practice but were censored if they switched to a previously trialed medication class., Main Outcomes and Measures: Incident cancer, excluding nonmelanoma skin cancer, after at least 90 days and within 2 years of initiation of biologic or targeted synthetic DMARDs. Outcomes were associated with the most recent drug exposure., Results: Of the 25 305 individuals who initiated treatment and who met the inclusion criteria, most were female (19 869 [79%]), had a median age of 50 years (IQR, 42-56 years), and were from the South US (12 516 [49%]). Of a total 27 661 drug exposures, drug initiations consisted of 20 586 TNFi exposures (74%), 2570 JAKi exposures (9%), 2255 abatacept exposures (8%), 1182 rituximab exposures (4%), and 1068 IL-6i exposures (4%). Multivariable Cox proportional hazards regression analysis showed that rituximab was associated with a higher risk of incident cancer compared with TNFis (hazard ratio [HR], 1.91; 95% CI, 1.17-3.14), followed by abatacept (HR, 1.47; 95% CI, 1.03-2.11), and JAKis (HR, 1.36; 95% CI, 0.94-1.96)., Conclusions and Relevance: In this cohort study of individuals with RA and new biologic or targeted synthetic DMARD exposures, individuals initiating rituximab, abatacept, and JAKis demonstrated higher incidence rates and statistically significantly increased risks of incident cancers compared with those initiating TNFis in the first 2 years after initiation of biologic or targeted synthetic DMARDs. Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.

The relationship between cancer and primary Sjögren's syndrome (pSS) is uncertain. While the increased risk of hematological malignancies is well-known, data on the comparative incidence of solid neoplasms is conflicting. This study aimed to explore the associations between cancer and pSS. This nationwide population-based retrospective study from the French health insurance database (PMSI) evaluated patients hospitalized with new-onset pSS from 2011 to 2018 against age- and sex-matched hospitalized controls (1:10). The incidence of hematological malignancies and solid neoplasms was compared between the two groups. Mortality and multiple cancer incidence were also evaluated. Adjusted Hazard Ratios (aHR) calculations included confounding factors, such as low socioeconomic status. Among 25,661 hospitalized patients with pSS versus 252,543 matched patients (median follow-up of 3.96 years), we observed a higher incidence rate of lymphomas (aHR, 1.97 [95% CI, 1.59-2.43]), Waldenström macroglobulinemia (aHR, 10.8 [6.5-18.0]), and leukemia (aHR, 1.61 [1.1-2.4]). Thyroid cancer incidence was higher (aHR, 1.7 [1.1-2.8]), whereas bladder and breast cancer incidences were lower (aHR, 0.58 [0.37-0.89] and 0.60 [0.49-0.74], respectively). pSS patients with breast cancer exhibited a lower mortality rate. A limitation was that the database only encompasses hospitalized patients, and immunological and histological details are not listed. We confirmed the increased risk of hematological malignancies and thyroid cancers among patients with pSS. The lower risk of breast cancer suggests a role of hormonal factors and raises questions of the concept of immune surveillance within breast tissue. Epidemiological and translational studies are required to elucidate the relationships between pSS and cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.