Individuals with a history of atopic disease, such as asthma and eczema (a.k.a. atopic dermatitis), are at significantly increased risk for developing osteoarthritis (OA), analysis of medical insurance claims indicated.
With some 110,000 people with asthma or atopic dermatitis matched to the same number of individuals without these conditions, the odds of developing OA were higher by 58% (95% CI 55-62) for those with atopy, according to Matthew C. Baker, MD, MS, of Stanford University in California, and colleagues.
People who had diagnoses of both asthma and atopic dermatitis were at specially high risk for OA, the group reported in Annals of the Rheumatic Diseases, with an odds ratio of 2.15 (95% CI 1.93-2.39).
The findings add to previous studies suggesting that immune dysregulation does play a role in OA, even though drugs used for autoimmune diseases (including biologic agents as well as older products such as methotrexate and hydroxychloroquine) have consistently been ineffective against this common and debilitating condition.
As Baker and colleagues observed, studies have identified increased activity of mast cells — which hold a prominent place in atopic disease pathology — in OA-affected synovial tissue. Other research going back decades has linked variants in certain cytokine receptors to OA.
With the new study added, it increasingly appears that “allergic pathways may contribute to the development of OA,” Baker’s group wrote. “If this is indeed true, non-atopic patients may also benefit from the use of treatments that inhibit mast cells and allergic cytokines to treat or prevent OA.”
The researchers didn’t suggest specific drugs, but a 2021 review noted that a number of currently approved agents inhibit mast cell activation or downstream effects. These include the anti-IgE drug omalizumab (Xolair) as well as several tyrosine kinase inhibitors such as imatinib (Gleevec) and dasatinib (Sprycel).
Baker and colleagues drew on the Optum database of medical insurance claims from 2003 to 2019, plus Stanford’s own records from 2010 through 2020. The Optum dataset included 117,346 individuals with asthma or atopic dermatitis, including 4,395 with both conditions, plus about 1.25 million others who met basic criteria for inclusion (e.g., at least 7 years continuous enrollment in an Optum-affiliated insurance plan and lack of inflammatory arthritis diagnoses).
After propensity-matching, the researchers had 109,899 individuals in the atopic and non-atopic groups. They were then followed in the records for new diagnoses of OA occurring at least 2 years after first entering the Optum database with an atopy diagnosis. “Diagnoses” were defined as the first appearance of an ICD-9/10 code for OA.
In this dataset, OA developed at a rate of 26.9 cases per 1,000 person-years in the atopy group, versus 19.1 per 1,000 person-years among the non-atopic controls.
Another comparison examined the atopic individuals and controls with chronic obstructive pulmonary disease (COPD), as a test to see whether patients with non-allergic respiratory disease might show the same increased predilection for OA as seen with atopy. They did not: Baker and colleagues calculated an odds ratio of 1.83 (95% CI 1.73-1.95) for OA development in the atopic versus COPD groups.
The Stanford cohort was used for independent validation. It numbered 43,728 individuals with atopic disease and 70,699 without. It too showed a significantly increased risk for OA with atopy (OR 1.42, 95% CI 1.36-1.48) after adjusting for covariates such as age, sex, comorbidity burden, and body mass index.
Baker and colleagues acknowledged several limitations to the analysis. These included the reliance on administrative data, and particularly the use of ICD codes to indicate disease onset. “[O]ur study assumes that a patient has developed incident OA at the time of receiving an ICD code for OA, which might not be the case,” the researchers cautioned. “It is possible that our outcome more accurately assesses when a patient has developed symptomatic OA to a large enough degree that the clinician acknowledges it through ICD coding.”
Other limitations included a lack of data on some potentially important confounders such as history of joint trauma and exercise habits and information about the severity of atopy or OA as well as patients’ use of over-the-counter medications. The latter factors might play into the clinical recognition of OA, as patients obtaining symptomatic relief from non-steroidal anti-inflammatory drugs may not receive a formal diagnosis until the severity worsens, the team noted.
The study was supported by U.S. government grants.
Baker and colleagues declared they had no relevant financial interests, although one co-author reported employment at Chinook Therapeutics.
Annals of the Rheumatic Diseases
Source Reference: Baker M, et al “Increased risk of osteoarthritis in patients with atopic disease” Ann Rheum Dis 2023; DOI: 10.1136/ard-2022-223640.