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Background: Potential associations between targeted therapies and a new cancer in patients with inflammatory arthritis (IA) and a previous malignancy are a frequent concern in daily rheumatology practice., Objectives: To develop points to consider (PTC) to assist rheumatologists when initiating a targeted therapy in the context of a previous malignancy., Methods: Following EULAR standardised operating procedures, a task force met to define the research questions for a systematic literature review and to formulate the overarching principles (OPs) and the PTC., Results: The group formulated five OPs; seven PTC were formulated concerning the initiation of targeted therapies in patients with active IA and a previous malignancy in remission and one PTC concerning patients with active IA who were not in cancer remission. Major themes included (a) the need to assess the individualised risk of cancer recurrence based on the characteristics of the patient, cancer and the underlying disease; (b) the importance of engaging with specialists caring for cancer and defining treatment based on a shared decision between the patient and the rheumatologist; (c) the value of initiating without delay an appropriate targeted therapy for the treatment of the IA in patients in remission of their cancer; (d) the proposal to use Janus kinase inhibitors and abatacept with caution and in the absence of therapeutic alternatives, based on the absence of any data concerning their use in the context of previous malignancy., Conclusion: The 2024 EULAR points to consider provide guidance on the management of targeted therapies in patients with IA and a previous malignancy., Competing Interests: Competing interests: No., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ Group on behalf of EULAR.)

Background: Targeted therapies have been associated with potential risk of malignancy, which is a common concern in daily rheumatology practice in patients with inflammatory arthritis (IA) and a history of cancer., Objectives: To perform a systematic literature review to inform a Task Force formulating EULAR points to consider on the initiation of targeted therapies in patients with IA and a history of cancer., Methods: Specific research questions were defined within the Task Force before formulating the exact research queries with a librarian. We included studies reporting a relative risk measure of patients with a history of cancer initiating a targeted therapy or a conventional synthetic disease-modifying antirheumatic drug (csDMARD), regardless of the time since diagnosis of cancer. All relevant studies included in PubMed or Embase up to 15 July 2022 were included. Two reviewers independently performed standardised article selection, data extraction, synthesis and risk of bias assessment., Results: 14 published articles and one ACR abstract fulfilled the inclusion criteria. All studies were high-quality observational studies, representing a median follow-up from treatment initiation of 4.52 years among 4428 patients and 15 062 patient-years of follow-up for new or recurrent cancer.All patients had a history of cancer, most frequently solid cancer, most frequently receiving treatment for rheumatoid arthritis and most frequently treated with tumour necrosis factor-alpha inhibitors. Across these studies, the overall HR of cancer recurrence was 0.92 (95% CI 0.74 to 1.15) for patients receiving a targeted therapy versus a csDMARD., Conclusion: Overall, the targeted therapies and clinical contexts covered by the included studies were not associated with an increased risk of cancer recurrence as compared with csDMARDs., Competing Interests: Competing interests: Participants provided declarations of interest; the individual declarations will be attached as an online supplemental file., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ Group on behalf of EULAR.)

Introduction: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors., Methods: Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models., Results: Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV- 2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections., Conclusion: VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management., Methods: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed., Results: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies., Conclusion: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations., Competing Interests: Competing interests: MK: honoraria from Abbvie, BMS, Lilly, Novartis, Pfizer; TRDJR: grants from AbbVie, Takeda, UCB, Janssen, GSK and honoraria from Abbvie, Pfizer, Takeda, Lilly, Medimmune, Novartis, GSK, BMS, AstraZeneca, Janssen; XM: honoraria from BMS; COB: grants and honoraria from BMS and honoraria from Genetech/Roche, Sanofi/Regeneron; OL: grant from Gilead and honoraria from BMS, MSD, AstraZeneca, Janssen; JLe: grants from Novartis, Pfizer and honoraria from Abbvie, AstraZeneca, BMS, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; AM: grants from BMS, Merus and honoraria from Merck Serono, Lytix, BMS, Symphogen, Amgen, AZ/Medimmune, Servier, Gritstone, Pierre Fabre, EISAI, Sanofi; TS: honoraria from Pfizer, Lilly, Novartis, BMS, Abbvie, Sanofi; EHC: grants from Biogen, grants and honoraria from Amgen, Bio-Cancer, Roche, UCB, Pfizer, honoraria from Chugai Pharma, Abbvie, BMS, Celgene, Eli Lilly, Janssen, ObsEva, Regeneron, Sanofi, SynAct Pharma, Tonix, Gilead; LT: honoraria from Novartis; KB: grants from Abbvie, Novartis, Rheumaliga Baden-Württemberg and honoraria from MSD, Abbvie, BMS, Janssen, Lilly, Mundipharma, Novartis, Pfizer, Roche, UCB; KV: speaker fees from BMS; JLa: grants from Aveo and Pharmacyclics, grants and honoraria from Achilles Therapeutics, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche/Genetech and Immunocore, honoraria from AstraZeneca, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugen, Incyte, iOnctura, Kymab, Merck Serono, Secarna, Vitaccess and Covance; JBAGH: grants from BMS, Novartis and advisory boards and/or lectures for MSD, BMS, Roche, Novartis; J-EG: grants from BMS, UCB, Pfizer, Sanofi and honoraria from BMS, Lilly, Pfizer, Sanofi-Genzyme, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response., Methods: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management., Results: From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001)., Conclusion: Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs., Competing Interests: Competing interests: MB-B reports consulting and advisory boards for BMS and MSD France. AR reports being a member of Global, European and/or French Advisory Board in GU tumours and/or immunotherapy for Pfizer, Novartis, BMS, Roche, Astra Zeneca and MSD and received travel support from Pfizer, BMS, Roche, Astra Zeneca and MSD. SP reports consulting for BMS and travel support from MSD. AP-L has received honoraria and travel support from BMS and MSD. RV reports being one of the investigators for a clinical trial from BMS, consulting and advisory boards for BMS and MSD and travel support from BMS and MSD. All the others authors declared no conflict of interest for this work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)