EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

Abstract

BackgroundRheumatic 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.MethodsFirst, 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.ResultsThe 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.ConclusionThese statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors—is it time for a paradigm shift?

“…Acquiring a deeper understanding of the biology of immune checkpoints and their inhibition is crucial in order to approach more optimal management strategies. Several recommendations regarding the management of irAEs have been published to date [24][25][26][27].…”

“…According to recently published points to consider from the European League against Rheumatism (EULAR), symptomatic treatment including non-steroidal anti-inflammatory drugs and/or analgesics should be the initial treatment for mild-to-moderate rheumatic irAE [25]. Local treatment with intra-articular glucocorticoids can be considered in case of monoarthritis or oligoarthritis, with or without combination with symptomatic treatment.…”

Arthralgia Induced by BRAF Inhibitor Therapy in Melanoma Patients

“…However, only a minority of patients fulfilled the 2010 EULAR/ACR classification criteria of RA, with routine clinical documentation likely underestimating the number of joints involved when no rheumatologic assessment was performed. Similarly, for rheumatic immune-related adverse events induced by checkpoint inhibitors, only 20% of patients fulfilled the respective criteria [ 27 ]. In contrast to irAEs, no patient showed other symptoms of rheumatic disease beyond arthralgia, such as sicca or vasculitis.…”

“…Unspecific inflammatory parameters were found in 79% of patients with BRAFi-induced arthralgia, as found for almost three-quarters of ICI-treated patients with irAEs showing elevated CRP levels. Specific markers of rheumatic and connective tissue diseases were not detected in symptomatic patients, as is usually the case for irAEs [ 17 , 18 , 27 ]. This is of particular interest, as seropositivity for RF and ACPA is closely linked to a more aggressive course of disease and radiographic signs of bone damage [ 28 ].…”

Management of immune checkpoint inhibitor-induced polymyalgia rheumatica

“…We read with interest the relevant article by Kostine et al 1 describing the specific concerns for the diagnosis and management of rheumatic immune-related adverse events (irAEs), which are caused by immune checkpoint inhibitor (ICI) therapy. The authors recommend to consider glucocorticoid treatment if rheumatic irAEs are not sufficiently controlled by symptomatic treatment.…”