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Practice Guideline
. 2021 Jan;80(1):36-48.
doi: 10.1136/annrheumdis-2020-217139. Epub 2020 Apr 23.

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

Marie Kostine  1 , Axel Finckh  2 , Clifton O Bingham  3 , Karen Visser  4 , Jan Leipe  5   6 , Hendrik Schulze-Koops  6 , Ernest H Choy  7 , Karolina Benesova  8 , Timothy R D J Radstake  9 , Andrew P Cope  10 , Olivier Lambotte  11 , Jacques-Eric Gottenberg  12 , Yves Allenbach  13 , Marianne Visser  14 , Cindy Rusthoven  14 , Lone Thomasen  15 , Shahin Jamal  16 , Aurélien Marabelle  17 , James Larkin  18 , John B A G Haanen  19 , Leonard H Calabrese  20 , Xavier Mariette  21   22 , Thierry Schaeverbeke  23
Affiliations
Practice Guideline

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

Marie Kostine et al. Ann Rheum Dis. 2021 Jan.

Abstract

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.

Keywords: arthritis; autoimmunity; inflammation; multidisciplinary team care; treatment.

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Conflict of interest statement

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.

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