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  1. Marie Kostine1,
  2. Axel Finckh2,
  3. Clifton Bingham3,
  4. Karen Visser4,
  5. Jan Leipe5,
  6. Hendrik Schulze-Koops6,
  7. Ernest Choy7,
  8. Karolina Benesova8,
  9. Timothy R. Radstake9,
  10. Andrew Cope10,
  11. Oliver Lambotte11,
  12. Jacques-Eric Gottenberg12,
  13. Yves Allenbach13,
  14. Marianne Visser14,
  15. Cindy Rusthoven14,
  16. Lone Thomasen15,
  17. Shahin Jamal16,
  18. Aurélien Marabelle17,
  19. James Larkin18,
  20. John Haanen19,
  21. Leonard Calabrese20,
  22. Xavier Mariette11,
  23. Thierry Schaeverbeke1
  1. 1University Hospital of Bordeaux, Bordeaux, France
  2. 2University Hospitals of Geneva, Geneva, Switzerland
  3. 3Johns Hopkins University, Baltimore, United States of America
  4. 4Haga Hospital, The Hague, Netherlands
  5. 5University Medical Centre Mannheim, Mannheim, Germany
  6. 6University of Munich, Munich, Germany
  7. 7Cardiff University School of Medicine, Cardiff, United Kingdom
  8. 8University Hospital Heidelberg, Heidelberg, Germany
  9. 9University Medical Center Utrecht, Utrecht, Netherlands
  10. 10King’s College London, London, United Kingdom
  11. 11Le Kremlin-Bicêtre, Paris, France
  12. 12University Hospital of Strasbourg, Strasbourg, France
  13. 13Pitié-Salpêtrière University Hospital, Paris, France
  14. 14EULAR PARE Patient Research Partner, Netherlands, Netherlands
  15. 15Aarhus University Hospital, Aarhus, Denmark
  16. 16University of British Columbia, Vancouver, Canada
  17. 17Gustave Roussy, Paris, France
  18. 18Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom
  19. 19Netherlands Cancer Institute, Amsterdam, Netherlands
  20. 20Cleveland Clinic, Cleveland, United States of America


Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy (1). Since they represent a spectrum of new clinical entities and a robust evidence base is lacking, a task force was convened to harmonize expert consensus regarding their identification and management due to the lack of dedicated clinical trials.

Objectives To develop EULAR recommendations for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy, based on literature and expert opinion.

Methods Recommendations were developed according to the 2014 EULAR Standard Operating Procedures. The task force consisted of 19 clinical experts from Europe and North America (14 rheumatologists, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives. During the first meeting, the group defined the focus of the task force, the target population, and formulated research questions. A systematic literature research was performed by one fellow (MK) with the help of a librarian. Based on available evidence and using a consensus procedure, recommendations were developed during a second meeting. The level of agreement was determined by an anonymous voting process.

Results 4 overarching principles and 10 recommendations were developed. The overarching principles define the role of rheumatologists and highlight the shared decision-making process between patients, oncologists and rheumatologists. One recommendation addresses the referral process, two address the diagnosis, and five address the therapeutic strategy of cancer patients experiencing rheumatic, musculoskeletal, and systemic signs or symptoms while receiving immunotherapy. An additional recommendation was included to address pre-existing rheumatic conditions and the last focuses on the diagnostic approach before immunotherapy.

Conclusion These recommendations provide the basis of a EULAR consensus on the diagnosis and the management of rheumatic irAEs.

Reference [1] Calabrese LH, Calabrese C, Cappelli LC. Rheumatic immune-related adverse events from cancer immunotherapy. Nat Rev Rheumatol. 2018 Oct;14(10):569-579.

Disclosure of Interests Marie Kostine: None declared, Axel Finckh Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, A2Bio, Bristol-Myers Squibb, MSD, Roche, Pfizer Inc, and UCB, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Karen Visser: None declared, Jan Leipe Grant/research support from: Novartis, Pfizer; Scientific Support: Novartis, Pfizer, Consultant for: AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Roche, Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, Novartis, MSD, Pfizer, Roche, Sanofi, UCB, Hendrik Schulze-Koops Grant/research support from: Novartis, Pfizer, Roche, Consultant for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Paid instructor for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Speakers bureau: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Ernest Choy Grant/research support from: Amgen, Bio-Cancer, Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer, Roche, and Union Chimique Belge, Consultant for: Abbvie, Amgen, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celgene, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmacuetical, GlaxoSmithKline, Hospita, ISIS, Jazz Pharmaceuticals, Janssen, MedImmune, Merrimack Pharmaceutical, Merck Sharp & Dohme, Napp, Novimmune, Novartis, ObsEva, Pfizer, Regeneron, Roche, R-Pharm, SynAct Pharma, Sanofi-Genzyme, Tonix and Union Chimique Belge, Speakers bureau: Amgen, BMS, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Hospira, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, and Union Chimique Belge, Karolina Benesova Grant/research support from: Scientific Projects (IIT) I’m involved in as an investigator have been supported, but not initiated or designed by Abbvie and Novartis, Consultant for: Advisory board member on early disease detection for Novartis, Timothy R. Radstake: None declared, Andrew Cope: None declared, Oliver Lambotte: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Yves Allenbach: None declared, Marianne Visser: None declared, Cindy Rusthoven: None declared, Lone Thomasen: None declared, Shahin Jamal Consultant for: Consultant for Abbvie, Amgen, BMS, Eli Lilly, Pfizer, Janssen, Merck, UCB, Aurélien Marabelle: None declared, James Larkin: None declared, John Haanen Consultant for: Amgen, Merck, MSD, Helsinn, Tesaro and Hexaland, Leonard Calabrese Consultant for: Bristol-Myers-Squibb, Genentech and Astra-Zeneca., Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Thierry Schaeverbeke: None declared

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