Rapid granulomatosis with polyangiitis induced by immune checkpoint inhibition

Brom, Rob R. H. van den; Abdulahad, Wayel H.; Rutgers, Abraham; Kroesen, Bart-Jan; Roozendaal, Caroline; Groot, Derk Jan A. de; Schröder, Carolien P.; Hospers, Geke A.P.; Brouwer, Elisabeth

doi:10.1093/rheumatology/kew063

Cited by 62 publications

(39 citation statements)

References 7 publications

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“…103 One patient with granulomatosis with polyangiitis was treated with oral cyclophosphamide. 105 For other systemic manifestations, hydroxychloroquine was safely prescribed for patients with CPI-induced lupus and scleroderma and in one patient with sarcoidosis. 48 95-100 157 Four patients with scleroderma-like syndromes received mycophenolate mofetil.…”

Section: Recommendationmentioning

confidence: 99%

“…87 Rituximab was also used in one patient with acral vasculitis without improvement and the need of surgical amputation. 105 7. The decision to hold or to continue the cancer immunotherapy should be based on the severity of rheumatic immune-related adverse events, the extent of required immunosuppressive regimen, the tumour response and its duration, as well as the future oncology treatment plan, in a shared decision with the patient (LoE 5; LoA 9.4).…”

Section: Recommendationmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Recommendationmentioning

confidence: 99%

Section: Recommendationmentioning

confidence: 99%

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

et al. 2020

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“…In human, a defective co-inhibitory PD1/PDL-1 axis is associated with a number of autoimmune diseases such as systemic lupus erythematosus and AAV (14,15). In addition, targeted blockade of this system promotes the development of AAV (16). The B-and T-Lymphocyte Attenuator (BTLA) is an Ig superfamily member molecule and interacts with the herpes virus entry mediator (HVEM), a member of the TNFR family (13,17,18).…”

Section: Introductionmentioning

confidence: 99%

The Co-inhibitor BTLA Is Functional in ANCA-Associated Vasculitis and Suppresses Th17 Cells

et al. 2019

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Objectives: The activation and inhibition of T-cells has been well-studied under physiological conditions. Co-inhibition is an important mechanism to keep effector T-cells in check. Co-inhibitors mediate peripheral self-tolerance and limit the immune response. Dysfunctional co-inhibition is associated with loss of T-cell regulation and induction of autoimmunity. Therefore, we investigated the co-inhibitor Band T-Lymphocyte attenuator (BTLA) in ANCA-associated vasculitis (AAV). Methods: Fifty-six AAV patients and 32 healthy controls (HC) were recruited. Flow cytometry was performed to investigate the expression of BTLA on T-cells. Double negative T-cells were defined as CD3 + CD4 − CD8 −. To assess the functionality of BTLA, CFSE-labeled T-cells were stimulated in presence or absence of an agonistic anti-BTLA antibody. In addition, impact of BTLA-mediated co-inhibition on Th17 cells was studied. Results: AAV patients in remission had a decreased expression of BTLA on double negative T-cells (CD3 + CD4 − CD8 −). On all other subtypes of T-cells, expression of BTLA was comparable to healthy controls. TCR-independent stimulation of T-cells resulted in down-regulation of BTLA on Th cells in AAV and HC, being significantly lower in HC. Co-inhibition via BTLA led to suppression of T-cell proliferation in AAV as well as in HC. As a result of BTLA mediated co-inhibition, Th17 cells were suppressed to the same extent in AAV and HC. Conclusion: BTLA expression is altered on double negative T-cells but not on other T-cell subsets in quiescent AAV. BTLA-induced co-inhibition has the capacity to suppress Th17 cells and is functional in AAV. Thus, BTLA-mediated co-inhibition might be exploited for future targeted therapies in AAV.

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“…The majority of patients received oral or intravenous corticosteroids and ICI was discontinued. Of note, a granulomatosis with polyangiitis occurred 1 week following anti-programmed cell death 1 (PD-1) agent for advanced melanoma, requiring methylprednisolone and oral daily cyclophosphamide 5. Unfortunately, data on cancer and vasculitis outcomes are often missing.…”

mentioning

confidence: 99%

Response to: ‘Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors’ by Delyon et al

Kostine¹,

Schaeverbeke²

2018

Ann Rheum Dis

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Rapid granulomatosis with polyangiitis induced by immune checkpoint inhibition

Cited by 62 publications

References 7 publications

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

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

The Co-inhibitor BTLA Is Functional in ANCA-Associated Vasculitis and Suppresses Th17 Cells

Response to: ‘Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors’ by Delyon et al

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