New Study Asks Why Lupus Patients Don’t Take Their Hydroxychloroquine

Hydroxychloroquine (HCQ) therapy may effectively manage systemic lupus erythematosus (SLE) in many patients, but that doesn’t mean patients will take it as often as they should. In fact, results from a recently published study found that about half of SLE patients were not adherent.¹

The study was led by Lucy H. Liu, MD, MPH, a rheumatology fellow at the University of California, San Francisco, who at the time of the study was an internal medicine resident at Kaiser Permanente Oakland Medical Center. The researchers acknowledged that poor adherence to HCQ is often hard to understand. The fear of adverse effects, patient perceptions of drug efficacy, depression and complex medication regimens all may play a role.

The Study

For their study, Dr. Liu and co-researchers decided to measure the World Health Organization’s (WHO) five dimensions of adherence for chronic conditions:²

• Socioeconomic status, which refers to wealth, education and occupation (and can also reflect health literacy and barriers to care);
• Patient-related factors, such as beliefs and attitude regarding treatment, which may be influenced by age and culture;
• Condition-related factors, such as co-morbidities, functional limitations and overall disease complexity;
• Therapy-related factors, which can include medication regimen complexity; and
• Health system factors, including integration, care coordination and access to care.

This retrospective study included 1,956 adult patients who were seen at Kaiser Permanente Northern California from 2006–2014, all of whom had SLE and two or more consecutive prescriptions for HCQ. Ninety percent of the study population was female, and the mean age was 47.

Researchers used the medication possession ratio as the primary outcome. The medication possession ratio is a well-established measure of medication adherence in electronic database research and is defined as the number of days of dispensed medication divided by the total days of follow-up. Researchers also stratified patients by adherence less than 80% or greater than 80%. Electronic medical records and 2010 census data were used to obtain predictor variables.

By using Kaiser Permanente patients, researchers could analyze patients who had easy access to its pharmacies and often had a fixed drug co-pay of $5 to $20. The study excluded patients with contraindications to HCQ, such as retinopathy, toxic maculopathy and allergy.

The Results

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Among the patients included, only 58% had 80% or higher HCQ adherence. Of those with adherence of 80% or higher, the mean adherence was 96%. For those with adherence lower than 80%, the mean adherence was 51%.

After an adjusted analysis, an age of 65–89 years, white race, an estimated glomerular filtration rate of 60–89 mL/min/1.73 m² (vs. 90 mL/min/1.73 m² or higher) and a larger number of rheumatologist visits in the year before baseline (three visits or more) were all associated with better adherence. More frequent visits are a marker of SLE severity, the researchers pointed out.

Mycophenolate mofetil use was somewhat inversely associated with the odds of adherence, but prednisone and angiotensin-converting enzyme-inhibitor use were not. Healthcare-system factors did not appear to affect adherence.

The median household income was $78,710 in the adherent group as compared with $77,425 in the non-adherent group. “None of the four variables measuring socioeconomic status differed between adherent and non-adherent patients,” Dr. Liu and co-researchers wrote. Gender and language also were not associated with adherence.

Patient education about the value of HCQ, online interactions, social media HCQ group participation and visits to the rheumatologist all may help improve adherence, the researchers wrote.

A Complex Problem

Dr. Liu says she and her research colleagues were surprised to learn that HCQ adherence was so low in an integrated healthcare system where care is coordinated. “So much effort has been put in to support adherence, yet only a little more than half the patients are taking hydroxychloroquine as prescribed,” she says.

The researchers were also surprised to find that socioeconomic status and education level did not appear to influence adherence. “This study illustrates that medication and adherence is a very complex behavior that’s not just about access to care, but more importantly, about patients’ beliefs regarding their medications, their relationship with their rheumatologists and their trust in the medical system. In order to improve adherence, our interventions must focus on understanding and addressing these beliefs,” Dr. Liu says.

One possible reason adherence may be low is a concern over HCQ’s side effects, including the risk for long-term retinal toxicity. However, rheumatologists spend a good amount of time explaining the drug and advising patients to undergo annual ophthalmologist screenings to detect any potential problems.

A more pressing concern, Dr. Liu has observed, is patients who discontinue the medication because they don’t feel it works. “[HCQ] has a long onset of action, and patients often don’t notice an immediate difference [as] they do with something like prednisone,” she says. “Many patients feel it’s not worth the risks of taking the medication if they don’t feel noticeably better.”

This is yet another reason why Dr. Liu spends time with patients to set expectations for HCQ use and to emphasize how important the drug is to treat SLE.

Takeaways

Candace Feldman, MD, MPH, ScD, a rheumatologist at Brigham and Women’s Hospital, Boston, says these and similar findings from other studies suggest physicians need to talk to patients about medication adherence. “[Although] certain factors in this study were modestly associated with increased odds of non-adherence, there was no one factor that clearly dominated this association, suggesting that adherence is complex, multifaceted and hard to predict,” says Dr. Feldman, who is also an assistant professor of medicine at Harvard Medical School in Boston and a member of the Lupus Foundation of America Medical-Scientific Advisory Council.

Doruk Erkan, MD, MPH, an associate physician-scientist at the Barbara Volcker Center for Women and Rheumatic Diseases, an associate attending rheuma­tologist and clinical researcher at the Hospital for Special Surgery, New York, and an associate professor of medicine at Weill Cornell Medicine, New York, says HCQ adherence among his SLE patients is around 60%. He has noticed that patients attempt to self-manage their disease by stopping or using lower-than-prescribed doses of HCQ.

“The [study] findings help us better predict the risk of medication non-compliance while managing lupus patients,” says Dr. Erkan. 

Vanessa Caceres is a medical writer in Bradenton, Fla.

References

1. Liu LH, Fevrier HB, Goldfien R, et al. Understanding non-adherence with hydroxychloroquine therapy in systemic lupus erythematosus. J Rheumatol. 2019 Feb 1. [epub ahead of print]
2. World Health Organization. Adherence to long-term therapies: Evidence for action. 2019 Apr 9.