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Adherence to biologic agents for the treatment of moderate to severe asthma varies according to where patients have their shots administered. Adherence rates are lower among those who are always treated in a clinic than it is among those who self-inject at home, a retrospective study suggests.

“I think there are a couple of explanations for this, the first assumption [being] that for patients who are less likely to be adherent, rockford school of medicine we’re going to recommend the clinic [not home use],” Hayden Bosworth, PhD, professor and vice chair for education and research professor in the Department of Medicine, Psychiatry, and Behavioral Sciences, School of Nursing, Duke University Medical Center, Durham, North Carolina, told Medscape Medical News.

“So, I think we need to do a better job at identifying people and matching them with the right drug and then educating primary care physicians that these patients should be referred to a specialist. The whole process should be based on shared decision-making and communication between the patient and provider to match patients with what will work best for them,” Bosworth stressed.

The study was published online in The Journal of Allergy and Clinical Immunology: In Practice.

Data Assessment

Data from the Optum Clinformatics Data Mart were assessed for the period January 1, 2015, to April 30, 2020. A total of 3932 patients were included. Patients were categorized into groups according to the site where they received their treatment: the clinic-only group (almost 74% of the cohort); the self-injection at home group (20%); and the hybrid group (mixture of clinic and self-administration; approximately 6%). The biologics used included dupilumab (Dupixent), mepolizumab (NUCALA), benralizumab (Fasenra), and reslizumab (Cinqair). Of those agents, duplilumab, mepolizumab, and benralizumab can be administered at home; reslizumab must be administered at a provider facility. For the study, adherence was “the proportion of the observed over the expected biologic dose administrations received within 6 months from initial therapy.”

“Biologics adherence was relatively lower for Clinic-only (0.75)…compared to Home (0.83)…and Hybrid (0.83),” Bosworth and colleagues report. Factors associated with biologic adherence also differed by site of administration. For example, in the adjusted model for the clinic-only group, a 10-year increase in age was associated with a 1% higher adherence rate (adjusted rate ratio [aRR] = 1.01; 95% CI, 1.00 – 1.03).

Geographic variation in adherence rates also differed in the clinic group. Adherence was 6% higher among patients in the Midwest (aRR = 1.06; 95% CI, 1.02 – 1.1) compared to those in the South. Adherence also differed by level of education; among those with a high school education or less, the adherence rate was 5% lower (aRR = 0.95; 95% CI, 0.91 – 0.99) than among those with a bachelor’s degree.

Adherence differed only marginally by household income. The adherence rate was 5% higher among those with a household income of less than $40,000 compared to those with a household income of between $40,000 and $99,000, the investigators note (aRR = 1.05; 95% CI, 1 – 1.1). Some indicators of asthma severity were also associated with greater adherence in the clinic-only group. These included seeing any specialist during the prior 6 months and the presence of comorbidities, such as depression.

Adherence rates dropped with increasing cost for the prescribed biologic. There was a 2% decrease in adherence for each increase of $1000 in cost (aRR = 0.98; 95% CI, 0.96 – 1.00). Among patients whose index asthma season was the fall, the adherence rate was 5% lower than among those whose index season was the spring (aRR = 0.95; 95% CI, 0.91 – 0.99), the authors note.

Race/Ethnicity Differences

Among patients who administered their biologic at home, adherence rates were 16% lower for Black patients compared to White patients (aRR = 0.84; 95% CI, 0.72 – 0.99). They were 13% lower for Hispanic patients (aRR = 0.87; 95% CI, 0.77 – 0.99). Insurance status in the same group also made a difference, with Medicare patients having a 26% lower adherence rate (aRR = 0.74; 95% CI, 0.66 – 0.83) compared to commercially insured patients.

Conversely, severity indices were associated with higher adherence rates, including any specialist visit in the prior 6 months (aRR = 1.14, 95% CI, 1 – 1.29) as well as respiratory infections (aRR = 1.09; 95% CI, 1 – 1.18).

“Similarly, for Hybrid patients, biologics adherence differed by income [and] socioeconomic status,” Bosworth and colleagues point out. Not unexpectedly, among patients with dementia, the adherence rate was 33% lower than among those without dementia (aRR = 0.67; 95% CI, 0.48 – 0.95).

In the adjusted model, adherence was not significantly associated with an emergency department (ED) visit of any nature over the course of a year among patients in either the clinic-only group or the home group.

However, in the multivariable model, Black race, Medicare insurance, and certain comorbidities, such as depression, were associated with a higher risk of visiting the ED during 1 year of follow-up in both the clinic-only and the home group. “Conversely, in the adjusted model for the Hybrid subgroup, a 10 percentage point increase in…adherence was associated with a 9% decrease in hazard for 1-year, all-cause ED visits” (adjusted hazard ratio [aHR] = 0.91; 95% CI, 0.84 – 0.98), the authors note.

In the hybrid group, each 10-year increase in age was also associated with a 27% lower hazard for making an ED visit (aHR = 0.73; 95% CI, 0.60 – 0.88), while having a bachelor’s degree was associated with a 58% lower hazard of making an ED visit compared to having less education (aHR = 0.42; 95% CI, 0.19 – 0.96).

Conversely, depression was associated with an 81% higher risk of making an ED visit (aHR = 1.81; 95% CI, 1.09 – 3.02). Asked why seeing a specialist within the previous 6 months improved adherence, Bosworth felt that patients get more attention when seen in a specialist clinic. “Specialists are also more familiar with these drugs,” he noted, “so the good thing is that patients probably get better counseling at a specialist clinic. The bad thing is you have to go through a lot of hoops to get to see a specialist,” he said.

Bosworth also stressed that just because adherence to a biologic regimen appears to be less among Black and Hispanic patients than among White patients, it’s not their fault. “Here in the US, we use race as a ‘catch-all’ for what I think represents a more social, contextual issue — access is an issue, cost is an issue, and I also think particularly for Blacks it’s a trust issue,” he said.

“So we have to do a better job about thinking about culture and context. We know there are multiple factors that explain nonadherence, and we have to take responsibility for this and not blame the patient,” Bosworth reemphasized.

Other Factors Involved

Asked by Medscape Medical News to comment on the study, Sabina De Geest, PhD, RN, chair, Department of Public Health, University of Basel, Switzerland, noted that while the study took patient demographics and healthcare factors such as insurance into consideration, “meso” level factors, or how care is organized within a clinic, were not considered. “For instance, you might have a clinic where a lot of attention is paid to supporting patients in self-management practices and where the continuity of care is being tracked, so if patients do not show up, they are called in,” De Geest explained.

These factors in and of themselves are linked to adherence, she added. “So, if you have a care environment which is very tuned towards supporting patients, you will see better adherence,” she stressed. Investigators were not able to assess between-center differences regarding where patients were receiving their injections, where large center-effect differences in the level of patient adherence are often seen. “That doesn’t mean that this study is not valuable — absolutely not,” De Geest noted.

But a lot of adherence — or nonadherence — depends on where a patient is living, how accessible their care might be, and the cost of having the injection administered at the clinic or at home — “all elements that could be looked at to better understand what it is that drives nonadherence,” she said. She echoed what Bosworth suggested, which is to simply ask patients what their preferences are; if they ready to change from one treatment to another; if they are ready for injections; and where they prefer to receive their injection, at home or in the clinic. “All of these factors have to be taken into consideration,” De Geest stressed.

“And then you plan your medication treatment, taking patient preferences into consideration, and this will help patients to accept the new treatment and persist with it,” she reaffirmed.

The study was sponsored by Sanofi US. Bosworth reported having received research grants from the PhRMA Foundation, Sanofi, the NIH, and the VA, among others, as well as consulting for Sanofi, Novartis, Otsuka, Abbott, and others. De Geest has served as a consultant for Sanofi and Novartis.

J Allergy Clin Immunol Pract, Published online May 28, 2022. Abstract

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