These include arthralgia; monoarthritis, oligoarthritis or polyarthritis; reactive arthritis; psoriatic arthritis (PsA); remitting seronegative symmetrical synovitis with pitting oedema (RS3PE); tenosynovitis; enthesitis; non-inflammatory musculoskeletal conditions and osteoarthritis

These include arthralgia; monoarthritis, oligoarthritis or polyarthritis; reactive arthritis; psoriatic arthritis (PsA); remitting seronegative symmetrical synovitis with pitting oedema (RS3PE); tenosynovitis; enthesitis; non-inflammatory musculoskeletal conditions and osteoarthritis.41 44 46 51 66C77 Importantly, autoantibodies are often absent. 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. Keywords: treatment, arthritis, autoimmunity, inflammation, multidisciplinary team care Introduction Although the concept of immunotherapy in cancer is far from new, monoclonal antibodies targeting immunological checkpoints or checkpoint inhibitors (CPIs) represent a growing class of brokers across multiple tumour types and at all stages of disease. Brokers targeting the T-cell cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) Nifenazone or the programmed cell death-(ligand) 1 (PD-1/PD-L1) coinhibitory receptors marked a turning point in the success of immunotherapeutic approaches.1C3 By enhancing antitumour T-cell activity, unprecedented long-lasting tumour responses were observed in patients with unresectable or advanced metastatic disease.4C7 The clinical value of these immune CPIs, as single agents or in combination, is being investigated in various sound tumours and haematological malignancies, and their use is expanding rapidly.8 So far, the Food and Drug Administration and the European Medicines Agency approved seven immune checkpoint-blocking antibodies in selected cancers: one anti-CTLA-4 (ipilimumab), three anti-PD-1 (nivolumab, pembrolizumab and cemiplimab) and three anti-PD-L1 (atezolizumab, avelumab and durvalumab). The T-cell activation induced by CPIs commonly promotes inflammatory or autoimmune-like side effects, known as immune-related adverse events (irAEs).9 Compared with conventional cancer therapies, this spectrum of toxicities is unique and can affect any organ system, most frequently the skin, gastrointestinal tract, endocrine glands and lung. Among irAEs, specific rheumatic manifestations have been described rather rarely in randomised clinical trials, but are much more common in clinical practice. The clinical TMOD4 features of rheumatic irAEs have been Nifenazone described in a growing number of case series and reports.10 However, despite the growing interest for irAEs among rheumatologists, evidence is lacking for the optimal diagnostic approach and the management of these patients in ways that also permit effective antitumour therapy to continue. According to a recent survey, a large proportion of rheumatologists have limited experience and little confidence in managing rheumatic irAEs, highlighting the need for education and recommendations in this emerging condition.11 In 2017, the European Society for Medical Oncology developed clinical guidelines for the management of immune toxicities and mentioned the paucity of literature on management of rheumatic irAEs.12 Three other consensus recommendations have been proposed by the Society for Immunotherapy of Cancer, the American Society of Clinical Oncology and The National Comprehensive Cancer Network, which among others included the management of inflammatory arthritis, polymyalgia rheumatica and myositis.13C15 This European League Against Rheumatism initiative assembled international experts primarily from the rheumatology and immunology but also the oncology field with the explicit goal of generating Nifenazone the first set of recommendations for the diagnosis and the management of rheumatic irAEs arising as a direct consequence of CPI. Rheumatologists, Nifenazone but also in some countries internists and immunologists, have to play a pivotal role in developing with the oncologists a patient-centred approach to improve the management of rheumatic irAEs. While the initiative primarily set out to guide clinicians, it is noteworthy that there is limited and rapidly changing literature and that future additional studies can drastically change the profile for diagnosis and management. This area will be a continually evolving field; therefore, the accompanying comments may also serve as a framework for future longitudinal cohorts and/or clinical studies. Methods After approval by the European League Against Rheumatism Executive Committee, an international task force was convened to develop points to consider for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy. Among these members, were 19 clinical experts from Europe and North America (14 rheumatologists including 2 delegates of the European League Against Rheumatism young rheumatologists network EMEUNET, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives from the PARE network of patient research partners. The process adhered to the updated European League Against Rheumatism standardised operating procedures for the development of recommendations.16 In July 2018, the.