MCCs in adults with autoimmune and inflammatory rheumatic diseases: evidence to date and future directions

Abstract

Multiple chronic conditions (MCCs), also known as multimorbidity, are highly prevalent in adults with autoimmune and inflammatory rheumatic diseases (AIIRDs) and significantly complicate their management. This narrative review summarizes current literature on the epidemiology of MCCs in various AIIRDs, highlighting their association with adverse health outcomes and proposing future directions for care. MCCs are ubiquitous across AIIRDs, often exceeding rates seen in age-matched general populations, with prevalence as high as 86% in rheumatoid arthritis and 81.5% in systemic lupus erythematosus cohorts and notable patterns including cardiopulmonary and mental health disorders frequently observed. This substantial MCC burden is consistently linked to adverse outcomes, including increased all-cause mortality, reduced functional status, diminished health-related quality of life, accelerated disability, higher healthcare utilization, and increased costs, driven by chronic inflammation, lifestyle, and treatment effects. Therefore, rheumatology care must adopt a holistic, person-centered framework that actively recognizes and manages MCCs, leveraging multidisciplinary teams and integrating evidence-based interventions guided by frameworks such as the geriatric 5Ms and 5Ts to advance the science of MCCs in adults with AIIRDs and improve outcomes and optimize health-related quality of life in this complex patient population.

Introduction

Multiple chronic conditions (MCCs), also commonly called multimorbidity, ¹ are prevalent in adults with autoimmune and inflammatory rheumatic diseases (AIIRDs). While traditionally a disease-centric approach has prevailed in the management of adults living with AIIRDs, the care of patients with MCCs, especially older adults, necessitates a person-centric approach to care. Disease-centric care treats each medical condition in isolation, increasing the risk for fragmented care and excessive treatment burden, whereas person-centered care integrates multiple conditions around the individual patient’s goals, priorities, and function. The distinction lies not in deprioritizing any condition, but rather in deciding which outcomes matter most when no single disease dominates.

Multiple approaches have been used to define and measure MCCs, ranging from counts of coexisting conditions to the use of weighted indices such as the Charlson Comorbidity Index or the Rheumatic Disease Comorbidity Index.^2,3 More recently, machine learning techniques have been leveraged to identify distinct patterns, recognizing the inherent interconnectedness of conditions rather than considering them in isolation. ⁴

MCCs affect adults with AIIRDs disproportionately and complicate their care. Individuals with AIIRDs often experience a higher burden of comorbid conditions, including cardiovascular disease (CVD), ⁵ metabolic syndrome, ⁶ osteoporosis, ⁷ mental health disorders, ⁸ and frailty, ⁹ which may be driven by shared inflammatory pathways, lifestyle factors, or even treatment-related side effects (e.g., glucocorticoids). This confluence of conditions can obscure symptom presentation of the AIIRD, delay diagnosis, necessitate complex polypharmacy, thereby increasing the risk of serious drug-drug interactions and adverse drug events, ¹⁰ and limit treatment options for the underlying AIIRD. Importantly, risk in this context derives not only from the comorbid conditions themselves but also from the comedications they require: studies across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) demonstrate that patients receive significantly more analgesics, NSAIDs, and even opioids than disease-free controls from early in the disease course, and that optimizing AIIRD treatment strategy can mitigate this downstream comedication burden.^11,12 Ultimately, the presence of MCCs may lead to worse disease control, accelerated disability, reduced quality of life, increased healthcare utilization, and greater morbidity and mortality, underscoring the critical need for rheumatologists to adopt a holistic, integrated approach to patient management that addresses the entire spectrum of an individual’s health, rather than focusing solely on a single disease. ¹³

In this narrative review, we aim to summarize recent literature on the epidemiology of MCCs in adults with AIIRDs and their association with adverse health outcomes. We also propose a future research agenda aimed at developing best practices for caring for adults with AIIRDs and MCCs, drawing on available evidence relevant to the general population and other medical subspecialties.

Methods

We searched PubMed from inception to December 2025. Search terms included MCCs, multimorbidity, and RA, spondyloarthropathy, psoriatic arthritis, Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s syndrome, antiphospholipid syndrome, systemic sclerosis, and inflammatory myopathy. We reviewed manuscripts published in English. Where systematic reviews were available, we favored systematic reviews synthesizing available evidence over individual studies.

Prevalence and incidence of MCCs

Inflammatory arthritis

A recent systematic review of 39 studies on terms used to describe the presence of coexisting conditions in the context of RA reported varying terminology (use of either comorbidity or multimorbidity or both used synonymously). ³ Among adults with RA in a US administrative claims cohort (N = 277,782, mean age 55.6 years) between 2006 and 2015, cross-sectional prevalence and burden of MCCs based on 44 chronic conditions were significantly higher in those with (vs without) RA ¹⁴ (Table 1). When the same 44 chronic conditions were considered, prevalence in RA was found to be 86% compared to 71% in age, sex and county-matched non-RA comparators among residents of eight Minnesota counties. ¹⁵ In an Irish axial spondyloarthritis (axSpA) cohort (N = 734, mean age (SD) 45 (12)), 55% (n = 403) of adults with axSpA had at least one additional chronic condition, with the most common being obesity (27%), hypertension (21%), hyperlipidemia (16%), and depression (10%). ¹⁶ Similarly, a systematic review and meta-analysis of over 150,000 patients with PsA identified the five most prevalent conditions as hypertension (34%), metabolic syndrome (29%), obesity (27%), hyperlipidemia (24%), and any CVD (19%), with depression and pulmonary disease each affecting approximately 12%. ¹⁷ Cardiovascular risk is particularly prominent in PsA; 82% of patients newly diagnosed with PsA carry at least one cardiovascular risk factor, and 40% of all patients with PsA have three or more comorbid conditions. ¹⁸

Table 1.

MCCs in select AIIRDs.

Disease category	AIIRD	Study (author, year)	Population (N, age)	MCC definition	Prevalence	MCC patterns	Associated outcomes
Inflammatory arthritis	RA	England et al. (2023)	N = 277782; mean 55.6 years	⩾2 of 44 conditions	86%	Cardiometabolic, mental health, chronic pain clusters	Increased mortality, disability, reduced HRQoL
		Davis et al. (2020)	192	⩾2 Conditions	48% with ⩾2 comorbidities and 14% with ⩾4	Higher overall burden vs non-RA	Increased healthcare utilization
	axSpA	Fitzgerald et al. (2020)	N = 734; mean 45 years	⩾1 Condition	55%	Obesity, hypertension, hyperlipidemia, depression	Worse disease activity, functional impairment
	PsA	Gupta et al. (2024)	152,000 Patients in systematic literature review	⩾2 Conditions	High (varies)	Hypertension, metabolic syndrome, obesity, hyperlipidemia, cardiovascular disease	Greater pain, functional limitation, poorer quality of life
Connective tissue diseases	SLE	Figueroa-Parra et al. (2024)	N = 449 (established)	⩾2 (Multimorbidity), ⩾5 (substantial)	81.5%, 52.8%	Pulmonary circulation disor- ders, heart failure, interstitial lung disease	—
		Figueroa-Parra et al. (2024)	N = 270 (New-onset)	⩾2, ⩾5 conditions	57.0%, 22.6%	Pulmonary circulation disorders, neuropathy, and inflammatory and ulcerative skin conditions	—
		Kariniemi et al. (2021)	N = 1006; mean 45.5 years	Morbidities beyond SLE	91.2%	Musculoskeletal, cardiovascular and genitourinary conditions	—
		Gergianaki et al. (2021)	N = 399	⩾3 Physical comorbidities; 2+ Mental comorbidities	51.0 (Physical multimorbidity); 33.1 (mental multimorbidity)	Thyroid disease, obesity, dyslipidemia, mental health comorbidity	Increased SLE-related hospitalizations
		Medhat et al. (2020)	N = 575	⩾2 Conditions	34.7% (SLE onset > 50 years); 24.3 (SLE onset 16–50 years); 6.6 (SLE onset ⩽16 years)	Hypertension, osteoporosis	—
		Dudkova et al. (2025)	N = 122	⩾2 Conditions	94%	Hypertension, other cardiovascular disease, lung disease	–
	Systemic sclerosis	Fairley et al. (2025)	N = 2000	CCI ⩾4	20%	Hypertension, dyslipidemia, obstructive lung disease, malignancy, ischemic heart disease	Worse survival, poorer physical function
		Fairley et al. (2024)	N = 426	CCI ⩾4	17.8%	—	Increasing disability
Vasculitis	ANCA-associated vasculitis	Sarica et al. (2021)	N = 543	⩾2 Conditions	23% (1 year), 37% (10 years)	Osteoporosis, cardiometabolic conditions	Increased healthcare costs, mortality
Myositis	Idiopathic inflammatory myopathy	Fornaro et al. (2025)	N = 1558	⩾2 Non-rheumatic conditions (basic multimorbidity); ⩾3 non-rheumatic conditions affecting ⩾3 organ systems (complex multimorbidity)	35%, 14%	Multisystem involvement	Worse PROMIS scores, fatigue, function
Other AIIRDs	PMR/GCA	Partington et al. (2018)	—	Variable	—	Vascular disease, hypothyroidism	Possible malignancy overlap, surveillance bias

AIIRD, autoimmune and inflammatory rheumatic diseases; axSpA, axial spondyloarthritis; GCA, Giant Cell Arteritis; PMR, polymyalgia rheumatica; PROMIS, Patient-Reported Outcome Measurement Information System; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.

Connective tissue disease

Among adults in an established US systemic lupus erythematosus (SLE) cohort (N = 449) with a median age of 54.3 (IQR 42.2–65.4), multimorbidity (2+ chronic conditions) was present in 81.5% and substantial multimorbidity (5+ chronic conditions) in 52.8% at the time of cohort entry ¹⁹ (Table 1). SLE (vs no SLE) was associated with higher odds of multimorbidity after adjustment for age and sex (multimorbidity: OR 2.98, 95% CI 2.18–4.11, p < 0.001; substantial multimorbidity: OR 3.35, 95% CI 2.50–4.53, p < 0.001). Among adults in a new-onset US SLE cohort (N = 270) with median age of 48.0 (IQR 35.4–62.3), multimorbidity was present 57.0% and substantial multimorbidity in 22.6% at baseline. SLE (vs no SLE) was associated with higher odds of multimorbidity after adjustment for age and sex (multimorbidity: OR 2.27, 95% CI 1.59–3.27, p < 0.001; substantial multimorbidity: OR 2.93, 95% CI 1.77–4.96, p < 0.001). In a Finnish population-based cohort, morbidities “of interest” were identified in 91.2% of those with newly diagnosed SLE (N = 1006, mean age 45.5 years, SD 16 years) versus 66.7% of comparators (N = 3005). ²⁰ In an Australian systemic sclerosis cohort (N = 2000) with median age of 47 (IQR 36–57), multimorbidity, defined as a Charlson comorbidly index score of 4+, was noted ever during follow-up in 20% of participants at a median of 12 years (IQR 6–21) post-onset of systemic sclerosis. ²¹ Among a subset of participants with incident systemic sclerosis cohort (N = 426) with median age at onset of 53.0 (IQR 42.8–60.6), 17.8% were found to have multimorbidity. ²²

Vaculitis and inflammatory myopathy

In a longitudinal, multicenter data linkage study in a Scottish national cohort of 543 adults with ANCA-associated vasculitis (AAV; median age 58.7 years (range 48.9–68.0 years)) and 2672 matched controls (median age 58.7 years (range 48.9–68.0 years)), participants with AAV consistently exhibited a higher risk of developing individual morbidities, most notably osteoporosis (adjusted IRR 8.0, 95% CI 4.5–14.2). ²³ Furthermore, MCCs (⩾2 disorders) were significantly more prevalent in adults with AAV relative to comparators, reaching 23.0% at 1 year and 37.0% at 10 years. In a multinational cohort including participants with idiopathic inflammatory myopathies (N = 1558) with median age of 61 (IQR 49–70), 35% and 14% were found to have basic (defined by ⩾2 non-rheumatic conditions) and complex (defined by ⩾3 non-rheumatic conditions affecting ⩾3 organ systems) multimorbidity, respectively. ²⁴

Patterns of MCCs

When machine learning techniques were applied across commercial health insurance administrative claims (n = 226,850) and US Veterans Affairs electronic health records (120,780) databases to identify predominant MCCs patterns in adults with RA, cardiopulmonary, cardiometabolic, and mental health/chronic pain disorders clusters were noted, all of which were found to be overrepresented in RA compared to non-RA cohorts. ⁴ A systematic review of 41 studies on comorbidities in polymyalgia rheumatica (PMR) revealed consistent associations between PMR and vascular events (stroke, CVD, peripheral arterial disease), as well as hypothyroidism. ²⁵ While some studies indicated an increased risk of overall and specific malignancies in PMR, cancers detected within 6 months of PMR diagnosis were prone to misdiagnosis, potentially overlapping with PMR symptoms.

Relationship of MCCs with disease severity and clinical characteristics

In a US Veterans Affairs RA cohort (N = 2956, mean age 64.5 years), mental health/substance abuse (β 0.12, 95% CI 0.00–0.23), cardiovascular (β 0.25 (95% CI 0.12–0.38)), and chronic pain (β 0.21 (95% CI 0.11–0.31)) multimorbidity were associated with increased RA disease activity measured by DAS28 scores. ²⁶ Presence and severity of MCCs were strongly associated with worse axSpA disease outcomes, as indicated by higher Bath Ankylosing Spondylitis Disease Activity Index, Bath AS Metrology Index, Bath AS Functional Index, Health Assessment Questionnaire, and AS Quality of Life scores. Each additional condition further contributed to the worsening of outcomes. ¹⁶ Comorbid conditions also independently impair patient-reported outcomes beyond the contribution of PsA disease activity itself. In a single-center cohort of 267 patients with PsA, multimorbidity was present in 50% and significantly associated with worse bodily pain, physical functioning, and role-physical scores on the SF-36. ²⁷ Multiple baseline characteristics differed between those with and without multimorbidity, including age at systemic sclerosis onset (p < 0.01), smoking history (p < 0.01), absence of Scl-70 positivity (p < 0.01), and lack of affiliation with a racial or ethnic minority group (p < 0.01). ²²

Outcomes of MCCs

In a systematic review of 19 studies, multimorbidity was found to be a significant predictor of increased all-cause mortality, reduced functional status, and decreased health-related quality of life in individuals with RA. ²⁸ Among participants in the UK Biobank (N = 2566, 56% with age 60+), those with RA were classified into clusters of long-term conditions; distinct clusters, particularly those involving cancer or a combination of asthma, chronic obstructive pulmonary disease, and congenital heart disease, were linked to significantly increased risks of all-cause mortality, major adverse cardiac events, and emergency hospitalizations. ²⁹ The review also reported reduced mortality in adults with PMR in some studies, which was attributed to possible surveillance bias due to regular medical follow-up. ²⁵ In AAV, the presence of MCCs was associated with a substantial 3.89-fold increase in healthcare costs for those with 3+ morbidities. In a multivariable regression model relating baseline characteristics with survival, presence of multimorbidity was associated with worse survival (HR 1.57, 95% CI 1.30–1.91, p < 0.01); multimorbidity was also associated with worsening disability based on HAQ-DI score (regression coefficient +0.17 units, 95% CI 0.13–0.21, p < 0.01). ²² In a multivariable logistic regression model relating baseline characteristics with high-increasing functional disability trajectory, multimorbidity was associated with greater odds of high-increasing functional disability trajectory over 10-year follow-up (OR 3.1, 95% CI 1.1–8.8, p = 0.04). ²¹ Participants with idiopathic inflammatory myopathies and basic or complex multimorbidity had worse Patient-Reported Outcome Measurement Information System (PROMIS) Global physical health, Global mental health, physical function SF10a, fatigue 4a, pain visual analog scale, and fatigue visual analog scale scores than those without basic or complex multimorbidity (all p < 0.001). ²⁴

Discussion

MCCs are common in adults with AIIRDs across the age spectrum and are associated with significant morbidity and excess mortality (Figure 1). Adults with AIIRDs may be especially prone to MCCs due to the effects of chronic inflammation and long-term sequelae of cumulative organ damage, underscoring the importance of multidisciplinary care in this population. Rheumatologists often play a central role in the longitudinal care of adults with AIIRDs and have the opportunity to address MCCs in their patients through early recognition of comorbid conditions and by taking into consideration patient-centered goals and priorities, as well as overall treatment burden (Figure 2).

Figure 1.

Conceptual framework of MCCs in AIIRDs.

AIIRD, autoimmune and inflammatory rheumatic diseases; MCC, multiple chronic condition.

Figure 2.

Figure showing the putative multilevel impact of MCCs in AIIRDs.

AIIRD, autoimmune and inflammatory rheumatic diseases; MCC, multiple chronic condition.

MCCs are highly prevalent in the general population, particularly among older adults. In a 2023 US population-based study, 27.1%, 52.7%, and 78.8% of adults 18–44, 45–64, and 65+ years, respectively, shared that they had been diagnosed with MCCs. ³⁰ Of interest, recent growth in MCC prevalence has been most pronounced among young adults, with an increase from 21.8% in 2013, indicating that MCC burden and impact are of clinical relevance not only in older adults, but also in young adults, who are likely to accrue additional chronic conditions as they age. Among adults 18–44 years of age, obesity, depression, and hypercholesterolemia were the most common chronic conditions. Similarly, obesity, hypercholesterolemia, and hypertension were most common among adults 45–64 years of age while hypertension, hypercholesterolemia, and arthritis of any kind were the most common among adults 65 years of age and above. Presence of MCCs has been associated with disability, functional decline, decreased health-related quality of life, and increased healthcare utilization. ³¹ Rheumatologists are well-positioned to participate in whole-person care of patients with arthritis and AIIRDs, promoting weight loss, cardiovascular risk reduction, and mental health, providing opportunities to improve health and wellbeing.

In other subspecialties, it has been long recognized that MCCs occur frequently alongside anchor chronic conditions and have important implications for patient care and the outcomes of care. For example, among older adults hospitalized for acute myocardial infarction, up to 56.3% and 36.6% were found to have ⩾2 cardiac-related and non-cardiac-related chronic conditions, respectively; individuals with more chronic conditions, either cardiac or non-cardiac, were found to have significantly greater risk of dying or developing complications (i.e., atrial fibrillation, heart failure, stroke, or cardiogenic shock) while admitted. ³² A recent systematic review confirmed a similar association between MCCs and mortality among older adults with CVD, including myocardial infarction and heart failure, across cohorts. ³³ Further, among adults with chronic kidney disease across the age spectrum, MCCs have been found in 96%, most often hypertension and musculoskeletal disorders. As in CVD, individuals with MCCs in the setting of underlying chronic kidney disease have been found to have an increased risk of mortality. ³⁴ In addition, older adults with malignancies present with more comorbidities than similarly aged individuals without cancer. ³⁵ More than 50% of all older adults with cancer have at least one comorbidity that may impact their cancer treatment. ³⁶ MCCs significantly complicate cancer care by increasing treatment-related toxicities, impairing functional status, and ultimately leading to worse survival.

Adults with AIIRDs and MCCs may benefit from the development or adaptation of evidence-based, patient-centered strategies to meet their holistic needs. Medication management programs aimed at deprescribing (e.g., clinical decision aids), behavioral interventions addressing lifestyle pathways common to MCCs (e.g., physical activity apps), care coordination (e.g, case management support), and self-management options (e.g., educational apps) have been suggested as approaches to preventing or mitigating MCCs. ³⁷ Prior qualitative research conducted in the general population has highlighted challenges with self-management in the context of MCCs, including those related to ongoing physical and emotional symptoms, access to care, and communication with healthcare providers, and identified strategies to enhance self-management, including reframing, prioritizing, and changing beliefs, that may be incorporated into self-management strategies for adults with AIIRDs. Drawing on evidence from the general population of the favorable effects of comprehensive care programs ³⁸ and nurse practitioner-delivered care for MCCs, ³⁹ adults with AIIRDs and MCCs would benefit from continued integration of allied rheumatology professionals and other members of the multidisciplinary team into their care. Technological approaches to engaging adults with MCCs and their caregivers (e.g., supporting communication with the healthcare team, treatment guidance, and medication management), are likely to become of increasing relevance, but may require adaptation to those with AIIRDs to promote uptake. ⁴⁰ Design and evaluation of interventions aimed at improving the health of adults with AIIRDs and MCCs at the patient, provider, and system levels represent an important future direction. Although MCCs affect individuals with AIIRDs across the age spectrum, inclusion of older adults, who have been underrepresented historically in clinical trials related to AIIRDs, ⁴¹ in interventional studies is essential to ensuring that their unique needs are met. Consideration of the geriatric 5Ms framework (i.e., Mind, Mobility, Medications, Multicomplexity, What Matters Most), ⁴² which guide patient-centered clinical care for older adults, and 5Ts framework (Target Population, Team, Tools, Time, Tips to Accommodate), ⁴³ which guide age-friendly research for older adults, frameworks is critical to advancing both needs and inclusion of older adults in line with existing research priorities for older adults with MCCs.^{42 –44} The American Geriatrics Society/AGING Learning, Educating, and Researching National Initiative in Geriatrics (“LEARNING”) Collaborative aims to fill educational and training gaps in MCCs research. ⁴⁵

While rheumatologists may account routinely for individual comorbid conditions as they pertain to AIIRDs and their management, consideration of MCCs holistically in the context of AIIRD care may require reframing for some clinicians. Use of validated surveys and point-of-care clinical decision aid tools could facilitate streamlined integration of MCC-aligned care in rheumatology settings along with allied health professional involvement and technological approaches. Use of validated surveys and other standardized measures (e.g., claims-based indices ⁴⁶ ) to allow for more uniform collection of data on MCCs in research contexts and improved synthesis of associated findings, including in AIIRDs where data on MCCs are currently limited such as primary Sjogren’s syndrome and antiphospholipid syndrome, represents an important future direction.

Conclusion

The growing burden of MCCs profoundly shapes the lived experience and clinical trajectory of individuals with AIIRDs. Presence of MCCs is not simply an age-related phenomenon, but an inherent and significant aspect of AIIRDs across the lifespan, driven by chronic inflammation, treatment effects, and shared risk factors. The high prevalence of distinct multimorbidity patterns, as exemplified in RA cohorts, correlates directly with adverse impacts on functional status and health-related quality of life, as well as increased healthcare utilization and mortality. Rheumatology care would benefit from adopting a holistic, patient-centered framework that recognizes and actively manages MCCs beyond the primary rheumatologic diagnosis, leveraging multidisciplinary teams and integrating evidence-based interventions. This comprehensive approach is essential to improving health outcomes and optimizing the health and wellbeing of this complex and growing patient population.