1969: Multimorbidity and PROMIS Health Outcomes in Patients with Idiopathic Inflammatory Myopathies: Analysis from the COVAD Study

Marco Fornaro¹, Vincenzo Venerito², Florenzo Iannone³, Naveen R⁴, Elena Nikiphorou⁵, Mrudula Joshi⁶, Ai Lyn Tan⁷, Sreoshy Saha⁸, Samuel Shinjo⁹, Vishwesh Agarwal¹⁰, Nelly Ziade¹¹, Tsvetelina Velikova¹², Esha Kadam¹³, Marcin Milchert¹⁴, Ioannis Parodis¹⁵, Abraham Edgar Gracia-Ramos¹⁶, Lorenzo Cavagna¹⁷, Masataka Kuwana¹⁸, Johannes Knitza¹⁹, Ashima Makol²⁰, Dey Dzifa²¹, CARLOS ENRIQUE TORO GUTIERREZ²², CARLO VINICIO CABALLERO²³, Oliver Distler²⁴, Jessica Day²⁵, Hector Chinoy²⁶, Vikas Agarwal⁴, Rohit Aggarwal²⁷, Latika Gupta²⁸ and COVAD Study Group²⁹, ¹University of Bari, Grottaglie, Italy, ²Rheumatology Department, Università degli Studi di Bari, Bari, Italy, ³Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy, ⁴Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India, ⁵King's College London, London, United Kingdom, ⁶Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, India, ⁷University of Leeds, Leeds, United Kingdom, ⁸Mymensingh Medical College, Faridpur, Bangladesh, ⁹Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, Brazil, ¹⁰Mahatma Gandhi Missions Medical College, Lucknow, India, ¹¹Saint-Joseph University, Beirut, Lebanon, ¹²Department of Clinical Immunology, Medical Faculty, University Hospital "Lozenetz", Sofia University St. Kliment Ohridski, Sofia, Bulgaria, ¹³Seth Gordhandhas Sunderdas Medical College and King Edwards Memorial Hospital, Mumbai, India, ¹⁴Department of Internal Medicine, Rheumatology, Diabetology, Geriatrics and Clinical Immunology, Pomeranian Medical University in Szczecin, Szczecin, Poland, ¹⁵Karolinska Institutet, Stockholm, Sweden, ¹⁶Department of Internal Medicine, General Hospital, National Medical Center "La Raza", Instituto Mexicano del Seguro Social, Av. Jacaranda S/N, Col. La Raza, Del. Azcapotzalco, C.P. 02990, Mexico City, Mexico, ¹⁷Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, ¹⁸Nippon Medical School Graduate School of Medicine, Tokyo, Japan, ¹⁹Department of Internal Medicine 3 Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany, ²⁰Mayo Clinic, Rochester, MN, Rochester, MN, ²¹Department of Medicine and Therapeutics, University of Ghana School of Medicine and Dentistry, College of Health Sciences, Korle-Bu, Accra, Ghana, ²²Centro de Estudios de Reumatología y Dermatología SAS, Cali, Colombia, ²³REUMACARIBE IPS, Barranquilla, Colombia, ²⁴Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, ²⁵Walter and Eliza Hall Institute, Melbourne, Australia, ²⁶The University of Manchester, Sale, United Kingdom, ²⁷University of Pittsburgh, Pittsburgh, PA, ²⁸Royal Wolverhampton Trust, Wolverhampton/University of Manchester, United Kingdom, ²⁹-, -

Background/Purpose: Comorbidities have a profound impact on the quality of life (QoL), though global data on the burden of comorbidities and its impact on health outcomes and QoL in vulnerable groups such as Idiopathic inflammatory myopathies (IIMs) is scarce.

Methods: We studied the prevalence, distribution and clustering of comorbidities and multimorbidity among patients with IIM, AIRDs and healthy controls (HCs) and its impact on health outcomes, utilizing data from the COVAD 2 study, a global patient-reported e-survey consisting of 167 collaborators from 110 countries. Basic multimorbidity (BM) /Complex multimorbidity (CM) were defined as the co-occurrence of ≥2 non-rheumatic comorbidities & ≥3 non-rheumatic chronic conditions affecting ≥3 different organ systems1 respectively. Human Development Index (HDI) of their country was taken as a surrogate marker for socioeconomic status (SES). PROMIS global physical health (PGP), mental health (PGM), fatigue 4a (F4a) and physical function short form (SF10) were analysed using descriptive statistics and linear regression models. Hierarchical Clustering on Principal Components was performed to outline the grouping.

Results: Among 10740 respondents, 1558 IIMs (15.9%), 4591 other AIRDs (46.8%) and 3652 HCs (37.3%) were analysed. IIMs comprised mainly of DM (30.2%) and IBM (24.1%) whilst AIRDs comprised 2450 inflammatory arthritis (53.4%), 2050 CTDs (44.6%) and 235 systemic vasculitis (5.1%).
Individuals with IIMs exhibited high burden of any comorbidity (OR: 1.62 vs AIRDs and 2.95 vs HCs,p < 0.01), BM (OR 1.66 vs AIRDs and 3.52 vs HCs,p < 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs,p < 0.01), and mental health disorders (MHDs) (OR 1.33 vs AIRDs and 2.63 vs HCs,p < 0.01)(FIG 1A, global distribution depicted as FIG 2)
IIM patients with comorbidities (and MHDs) had worse physical function (low PGP, PGM, SF10 and higher F4a scores, all *p < 0.001). Worse physical function (PGP, SF10a, F4a) and mental health (PGM) was predicted by age, active disease, BM, and MHDs. Worse SF10a and F4a scores were also associated with female gender and country HDI respectively. (FIG 1B)
4 distinct clusters were identified among IIMs: Cluster 0: lower comorbidity burden and good health status Cluster 1: older patients with higher comorbidity burden and poorer health status Cluster 2: patients with higher prevalence of MHDs, lower PGP, PGM and higher F4a scores Cluster 3: older patients with average comorbidity burden and good health status.
DM, Anti-synthetase syndrome and necrotizing autoimmune myopathy were similarly represented in all clusters, while IBM and PM were more pre-dominant in clusters 1 (61.7% and 45.3%) and 3(36.4 and 34.6), while overlap myositis was more represented in clusters 2 (45.4%). (FIG 3)

Conclusion: Patients with IIMs have a higher burden of comorbidities with identifiable syndemic clusters that adversely impact physical and mental health, calling for optimized approaches for holistic patient management.
References:

1. Harrison C, Britt H, Miller G, Henderson J. Examining different measures of multimorbidity, using a large prospective cross-sectional study in Australian general practice. BMJ Open. 2014 Jul 1;4(7):e004694.

M. Fornaro: None; V. Venerito: None; F. Iannone: Abbvie, 2, 5, BMS, 2, 5, Janssen, 2, 5, Lilly, 2, 5, MSD, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, Roche, 2, 5, UCB, 2, 5; N. R: None; E. Nikiphorou: AbbVie/Abbott, 6, Celltrion, 6, Eli Lilly, 6, fresenius, 6, Galapagos, 6, Gilead, 1, 6, Pfizer, 6, Sanofi, 6; M. Joshi: None; A. Tan: Abbvie, 1, 6, Gilead, 6, Janssen, 6, Lilly, 6, Novartis, 6, Pfizer, 6, UCB, 6; S. Saha: None; S. Shinjo: None; V. Agarwal: None; N. Ziade: Abbvie, 6, Boehringer-Ingelheim, 6, Eli Lilly, 6, Janssen, 6, Newbridge, 6, Novartis, 6, Pfizer, 6, Pierre Fabre, 6, Roche, 6, sanofi, 6; T. Velikova: AstraZeneca, 6, Pfizer, 6; E. Kadam: None; M. Milchert: None; I. Parodis: Amgen, 5, 6, AstraZeneca, 5, 6, Aurinia Pharmaceuticals, 5, 6, Bristol-Myers Squibb(BMS), 5, 6, Elli Lilly and Company, 5, 6, F. Hoffmann-La Roche AG, 5, 6, Gilead Sciences, 5, 6, GSK, 5, 6, Janssen Pharmaceuticals, 5, 6, Novartis, 5, 6, Otsuka Pharmaceutical, 5, 6; A. Gracia-Ramos: None; L. Cavagna: None; M. Kuwana: AbbVie/Abbott, 6, Asahi-Kasei, 5, 6, Astellas, 6, AstraZeneca, 2, Boehringer-Ingelheim, 2, 5, 6, Chugai, 2, 5, 6, Corbus, 2, Eisai, 6, GlaxoSmithKlein(GSK), 2, Horizon, 2, Janssen, 6, Kissei, 2, MBL, 2, 5, Mitsubishi Tanabe, 2, 5, 6, Mochida, 2, 6, Nippon Shinyaku, 6, Ono, 5, 6; J. Knitza: None; A. Makol: Boehringer-Ingelheim, 1, Sanofi-Genzyme, 1; D. Dzifa: Roche, 6; C. TORO GUTIERREZ: AbbVie/Abbott, 6, Boehringer-Ingelheim, 6, Janssen, 6; C. CABALLERO: None; O. Distler: 4P-Pharma, 2, 5, 6, AbbVie, 2, 5, 6, Acceleron, 2, 5, 6, Alcimed, 2, 5, 6, Altavant Sciences, 2, 5, 6, Amgen, 2, 5, 6, AnaMar, 2, 5, 6, Arxx, 2, 5, 6, AstraZeneca, 2, 5, 6, Bayer, 2, 5, 6, Blade Therapeutics, 2, 5, 6, Boehringer Ingelheim, 2, 5, 6, Citus AG, 12, Co-Founder, Corbus Pharmaceuticals, 2, 5, 6, CSL Behring, 2, 5, 6, Galapagos, 2, 5, 6, Galderma, 2, 5, 6, Glenmark, 2, 5, 6, Gossamer, 2, 5, 6, Horizon Therapeutics, 2, 5, 6, Janssen, 2, 5, 6, Kymera, 2, 5, 6, Lupin, 2, 5, 6, Medscape, 2, 5, 6, Miltenyi Biotec, 2, 5, 6, Mitsubishi Tanabe, 2, 5, 6, MSD, 2, 5, 6, Novartis, 2, 5, 6, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143), 10, Prometheus Biosciences, 2, 5, 6, Redx Pharma, 2, 5, 6, Roivant, 2, 5, 6, Topadur, 2, 5, 6; J. Day: CSL limited, 5; H. Chinoy: AstraZeneca, 1, Biogen, 2, Eli Lilly, 5, GlaxoSmithKlein(GSK), 6, Novartis, 2, Orphazyme, 2, Pfizer, 1, UCB, 6; V. Agarwal: None; R. Aggarwal: Actigraph, 2, Alexion, 2, ANI Pharmaceuticals, 2, Argenx, 2, AstraZeneca, 2, Boehringer-Ingelheim, 2, 5, Bristol-Myers Squibb(BMS), 2, 5, CabalettaBio, 2, Capella Bioscience, 2, Corbus, 2, CSL Behring, 2, EMD Serono, 2, 5, Galapagos, 2, Horizon Therapeutics, 2, I-Cell, 2, Janssen, 2, 5, Kezar, 2, Kyverna, 2, Mallinckrodt, 5, Merck, 2, Octapharma, 2, Pfizer, 2, 5, Q32, 5, Roivant, 2, Sanofi, 2, Teva, 2; L. Gupta: None; C. Study Group: None.