Comorbidity Patterns and Identification of Clusters in >1,000,000 Patients Diagnosed with Osteoarthritis in Four Different European Countries: A ComOA Study

Abstract

Objectives: To identify comorbidity patterns at the time of diagnosis of osteoarthritis and to evaluate their risk of mortality at 10-years.

Methods: Data from 1,033,594 individuals with incident diagnosis of osteoarthritis were used from four European healthcare databases. Latent class analysis was used to identify clusters of comorbidities. Clusters were internally evaluated by their posterior probabilities and comorbidities prevalence, and externally validated by clinical characteristics not included in the clustering algorithm. Their association with age and sex adjusted ‘all-cause-mortality’ was assessed.

Results: We identified four consistent clusters across the four populations: "Relatively few morbidities/mild", "Musculoskeletal and mental health morbidities", "Cardiovascular morbidities" and "Multiple morbidities". The first cluster had the largest number of patients and the lowest median number of comorbidities (range 1 to 2) and was used as the reference in the mortality assessment. The second cluster had the highest proportion of women and an excess risk of mortality (ranging from 11% to 66%) compared to the referent cluster in three of the four populations. "Cardiovascular morbidities" had the highest proportion of men, whilst "Multiple morbidities" was the smallest cluster with the highest mean age and median of comorbidities (range 5 to 11). “Cardiovascular morbidities” and “Multiple morbidities” clusters had an excess mortality risk compared to the referent cluster in all populations (range 24% to 63% and 86% to 205%, respectively).

Conclusions: The consistent four clusters of comorbidities present in patients with osteoarthritis from different European populations may have a potential to inform patient care decision-making and healthcare resource allocation.

Funding: Foundation for Research in Rheumatology, The Swedish Research Council, Governmental funding of clinical research within the national health services (ALF), Österlund Foundation, Gustaf V 80-year Birthday Foundation, The Foundation for Individuals with Movement Disability in Skåne, The Swedish Rheumatism Association and Oxford NIHR Biomedical Research Centre.

Declaration of Interest: AK, ADI, JR, CC, ME, WZ were funded through FOREUM grant, directly or through their institution. AT declares consulting fees to Osteoarthritis and Cartilage journal JR was funded by the Swedish Research Council (2020-01103), Governmental funding of clinical research within the national health services (ALF), Österlund Foundation, Gustaf V 80-year Birthday Foundation, The Foundation for Individuals with Movement Disability in Skåne, and The Swedish Rheumatism Association. CM is director of the NIHR School for Primary Care Research and declares that Keele University have received funding for his time from NIHR, MRC, Versus Arthritis, BMS, and Dunhill Medical Trust. ME declares consultancy for Cellcolabs AB and Key2Compliance AB. SBZ declares independent research grants paid to her institution from EU, Dutch Arthritis Association and ZonMw, and consulting fees from Pfizer Infirst Healthcare. WZ declares serving as an advisory board for Ely Lilly (Ixekizumad, 2020) and Regeneron (Fasinomab, 2020). VS is a full-time employee at Boehringer-Ingelheim GmbH & Co. KG, and is part of the ESFORUM academic board. DPA’s research group has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma; and consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by SK and DPA's department. SK receives funding support from Amgen BioPharma outside of this work.

Ethical Approval: Research ethics was obtained according to each database requirement: SHR - SE: The use of pseudo anonymized healthcare data from the Skåne region was approved by the Lund University Ethics committee (Dnr 432-2011 and Dnr 2018/233). SIDIAP - ES: all participants records were previously collected and anonymised. Thus, no direct participant recruitment was done. The protocol of the study (number 4R19/011) was approved by the IDIAP Jordi Gol Clinical Research Ethics Committee. IPCI - NL: The scientific and ethical advisory board of the IPCI project approved the study (registration number 11/2019). CPRD - UK: The study has obtained the following ethics approvals: UK- Independent Scientific Advisory Council (ISAC) 19/30R.

Keywords: Osteoarthritis, Comorbidities, Clusters, Survival analysis, Multimorbidity