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Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients
  1. Sara Monti1,2,
  2. Alessandra Milanesi1,2,
  3. Catherine Klersy3,
  4. Alessandro Tomelleri4,
  5. Lorenzo Dagna4,
  6. Corrado Campochiaro4,
  7. Nicola Farina5,
  8. Francesco Muratore6,
  9. Elena Galli6,7,
  10. Chiara Marvisi7,8,
  11. Milena Bond9,10,
  12. Alvise Berti11,
  13. Roberto Bortolotti12,
  14. Roberto Padoan13,
  15. Franco Schiavon14,
  16. Mara Felicetti14,
  17. Carlotta Nannini15,
  18. Fabrizio Cantini15,
  19. Alessandro Giollo16,17,
  20. Maurizio Rossini18,
  21. Edoardo Conticini19,
  22. Bruno Frediani19,
  23. Fabrizio Conti20,
  24. Roberta Priori20,21,
  25. Marco Sebastiani22,
  26. Giulia Cassone23,24,
  27. Luca Quartuccio25,26,
  28. Elena Treppo25,26,
  29. Silvano Bettio27,
  30. Ariela Hoxha28,29,
  31. Marco Lovisotto29,
  32. Giacomo Emmi30,31,
  33. Irene Mattioli32,
  34. Pietro Leccese33,
  35. Roberto Caporali34,35,
  36. Lorenza Maria Argolini36,
  37. Rosario Foti37,
  38. Elisa Visalli37,
  39. Michele Colaci38,
  40. Carlo Salvarani6,7,
  41. Carlomaurizio Montecucco1,2
  42. On behalf of the Italian Society of Rheumatology Vasculitis Study Group
    1. 1 Dipartimento di medicina interna e terapia medica, Universita degli Studi di Pavia, Pavia, Italy
    2. 2 Reumatologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
    3. 3 UOS Epidemiologia Clinica e Biometria, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
    4. 4 Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS Ospedale San Raffaele, Milano, Italy
    5. 5 Unit of Immunology, Allergology and Rare Diseases, IRCCS Ospedale San Raffaele, Milano, Italy
    6. 6 Unit of Rheumatology, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
    7. 7 University of Modena and Reggio Emilia, Modena, Italy
    8. 8 Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
    9. 9 Rheumatology, Santa Chiara Hospital of Trento, Trento, Italy
    10. 10 Rheumatology, Brunico Hospital, Brunico, Italy
    11. 11 Center for Medical Sciences (CISMed), Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, and Division of Rheumatology, Santa Chiara Hospital, APSS, Trento, Italy
    12. 12 Rheumatology Unit, Santa Chiara Hospital of Trento, Trento, Italy
    13. 13 Department of Medicine DIMED, Division of Rheumatology, University of Padua, Padova, Italy
    14. 14 Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy
    15. 15 UOC Reumatologia ASl Toscana Centro, Santo Stefano Hospital Prato, Prato, Italy
    16. 16 Rheumatology Unit, Department of Medicine, University of Verona Faculty of Medicine and Surgery, Verona, Italy
    17. 17 Rheumatology Unit, Department of Medicine, University of Padua, Padova, Italy
    18. 18 Rheumatology Unit, University of Verona, Verona, Italy
    19. 19 Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
    20. 20 Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, University of Rome La Sapienza, Rome, Italy
    21. 21 Unicamillus, Saint Camillus International University of Health Sciences, Rome, Italy
    22. 22 Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
    23. 23 Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
    24. 24 Rheumatology Unit, Azienda Ospedaliero-Universitaria di Modena Policlinico di Modena, Modena, Italy
    25. 25 Division of Rheumatology, Department of Medicine, University of Udine, Udine, Italy
    26. 26 Division of Rheumatology, Department of Medicine, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
    27. 27 Rheumatology Unit, University of Padua, Treviso, Italy
    28. 28 Internal Medicine Unit, Department of Medicine, San Bortolo Hospital of Vicenza, Vicenza, Italy
    29. 29 General Internal Medicine Unit and Thrombotic and Hemorragic Unit, Department of Medicine-DIMED, University of Padua, Padova, Italy
    30. 30 Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy
    31. 31 Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia
    32. 32 Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, Firenze, Italy
    33. 33 Rheumatology Department of Lucania/IReL, Regional Hospital San Carlo, Potenza, Italy
    34. 34 Division of Clinical Rheumatology, ASST Gaetano Pini, Milano, Italy
    35. 35 Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, University of Milan, Milano, Italy
    36. 36 Rheumatology, ASST Gaetano Pini, Milano, Italy
    37. 37 Rheumatology Unit, AOU San Marco, Catania, Catania, Italy
    38. 38 Clinical and Experimental Medicine, Rheumatolgy Unit, University of Catania, Catania, Italy
    1. Correspondence to Dr Sara Monti, Dipartimento di medicina interna e terapia medica, Universita degli Studi di Pavia, Pavia, Lombardia, Italy; sara.saramonti{at}gmail.com

    Abstract

    Background Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce.

    Methods Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65–79 and ≥80 years old.

    Results The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23–91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65–79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2–3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors.

    Conclusions The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

    • Giant Cell Arteritis
    • Systemic vasculitis
    • Outcome Assessment, Health Care

    Data availability statement

    Data are available on reasonable request. Study protocol and raw data are accessible on reasonable request.

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    Data availability statement

    Data are available on reasonable request. Study protocol and raw data are accessible on reasonable request.

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    Footnotes

    • Handling editor Josef S Smolen

    • Twitter @tomelleri_a, @DrAleeG

    • Collaborators List of collaborators for the Italian Society of Rheumatology Vasculitis Study Group:-Alice Bartoletti (1. dipartimento di medicina interna e terapia medica, Università di Pavia, 2 Reumatologia, Fondazione IRCCS Policlinico San Matteo, Pavia);-Giovanni Zanframundo (1. dipartimento di medicina interna e terapia medica, Università di Pavia, 2 Reumatologia, Fondazione IRCCS Policlinico San Matteo, Pavia);-Elena Maria Baldissera (Unit of Immunology, Rheumatology, Allergy and Rare Diseases; IRCCS San Raffaele Hospital; Milan; Italy);-Chiara Asperti (Unit of Immunology, Rheumatology, Allergy and Rare Diseases; IRCCS San Raffaele Hospital; Milan; Italy);-Riccardo Bixio (Rheumatology Unit, Department of Medicine, University of Verona);-Gattamelata Angelica (Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy),-Giacomo Bagni (Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy).

    • Contributors All authors contributed to the development of the research project, collection of data and revision of the manuscript. All collaborators contributed to the collection of data and revision of the manuscript. SM

      acted as guarantor accepting full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.