
==== Front
Perm J
tpj
tpj
The Permanente Journal
1552-5767
1552-5775
The Permanente Press

39042384
10.7812/TPP/23.161
TPJ-23-161
Original Research
“Lupus Doesn’t Have Me, I Have Lupus”: Using Patient-Centered Interviews to Understand Medication Nonadherence
Macko Christopher A MD 1
Santos Roger PharmD 2
https://orcid.org/0000-0002-9931-467X
Ramalingam Nirmala D MPP 3
Tran Nicole MD, PhD 1 4
Zheng Sijie MD, PhD 4 5
Chen Patty Pei-chang MD 4 6
1 Department of Medicine, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA
2 Kaiser Permanente East Bay Pharmacy, Oakland, CA, USA
3 Graduate Medical Education, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA
4 The Permanente Medical Group, Oakland, CA, USA
5 Department of Nephrology, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA
6 Department of Rheumatology, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA
Nirmala D Ramalingam, MPP nirmala.d.ramalingam@kp.org
SZ and PP-cC contributed equally.

2024
23 7 2024
28 3 8490
© 2024 The Authors.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Published by The Permanente Federation LLC under the terms of the CC BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.

Abstract

Background

Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus and associated with higher morbidity and mortality. Low medication adherence correlates with adverse clinical outcomes.

Methods

In a large, integrated health system at Kaiser Permanente East Bay Area, the authors identified mycophenolate mofetil (MMF) prescriptions for LN and collected patient demographics, medication adherence, and copay data. They interviewed patients with low medication adherence rates to understand contributing factors, such as side effects, cost, refill processes, and laboratory draws. Adherence was defined as a proportion of days covered at > 80%. The proportion of days covered is the number of days covered by a medication divided by the number of days in a defined period.

Results

Between November 30, 2021, and November 30, 2022, the authors identified 36 patients with LN on MMF. Almost a third (11/36) of these patients were nonadherent to medication. More than half (7/11) of these patients agreed to be interviewed. They identified the following causes of medication nonadherence: forgetfulness (57%, or 4/7), incomplete laboratory work (28%, or 2/7), medication cost (14%, or 1/7), and intentionally missed doses (14%, or 1/7). No patients identified medication side effects as a cause. The median 30-day copay for MMF was $4.55, and 28% (2/7) of patients paid $0 for their medications.

Conclusions

In the authors’ integrated health system, 69% of their patients with LN on MMF were adherent to their medication regimen. Forgetfulness was a challenge for the nonadherent patients. Kaiser Permanente East Bay Area provides convenient refills and laboratory draws; this likely facilitates medication adherence.

Disclaimer “Lupus Doesn’t Have me, I Have Lupus,” a Patient-Centered Quality Improvement Project to Increase Medication Adherence for Patients With Lupus Nephritis was presented as a poster at 2023 American College of Rheumatology Conference.
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pmcBackground

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect any organ system. Damage to organs and cells is caused by tissue-binding autoantibodies and immune complexes. Its pathogenesis is due to the increased production of immunogenic forms of nucleic acid, which then triggers the immune system. The multifactorial etiology involves genetic, environmental, and epigenetic changes.1 Of those affected by SLE, 90% are women of childbearing age. In the United States, SLE is more common in Asian, Black, and Hispanic patients than non-Hispanic white (NHW) patients.2

Lupus nephritis (LN) is the most common form of kidney injury in patients with SLE. It develops in approximately 50% of patients with SLE and is a leading cause of death within the first 10 years of the disease.1,3 LN develops within 3 years of diagnosis and is sometimes present on initial diagnosis.3 Although the incidence of SLE is much less common in men than women, men are more likely to progress to LN.4

Morbidity and mortality are higher in patients with LN when compared to patients with SLE without LN.3,5 The likelihood of LN progressing to end-stage kidney disease is as high as 22% at 15 years. The standardized mortality rate has been estimated to be nearly 7 times higher when compared to the general population.6–8

The treatment of LN involves immunosuppressive therapy using induction with pulse dose steroids and either cyclophosphamide (National Institutes of Health or Euro-Lupus protocol) or mycophenolate mofetil (MMF).3 Calcineurin inhibitors (eg, tacrolimus, cyclosporine, and voclosporin) and the monoclonal antibody belimumab have also gained traction in combination with cyclophosphamide or MMF as part of induction therapy.9–11 Maintenance therapy is continued with MMF or, less frequently, azathioprine (which is preferred for use during pregnancy).12

Achieving complete clinical response is essential for maintaining kidney health. One study showed that the 10-year kidney survival rate was 94% in patients who had achieved complete remission of their LN. This was markedly higher than the 45% and 19% 10-year kidney survival rate of patients who had achieved partial or no remission, respectively.13 Another study showed that chronic kidney disease–free survival was much improved in partial or complete responders compared to nonresponders.14

Effective immunosuppression has not only improved kidney survival rates but has also decreased overall mortality. Before glucocorticoids were available, the 5-year survival rate of patients with LN was 44%. With modern-day treatment regimens, including both steroids and immunosuppressants, the 5-year survival rate exceeds 90%.15 Despite these advances, morbidity and mortality remain high in patients with LN, and nonadherence to medication likely contributes to this.15–17

Nonadherence is defined as taking a prescribed medication less than 80% of the time.18 Nonadherence to treatment regimens is common for patients with SLE and can lead to poor outcomes.17–22 One study of a publicly funded US clinic showed that less than a quarter of patients with SLE adhered to their treatment regimen.20 The causes of high rates of nonadherence are complex. Medication cost, patient misunderstanding, adverse drug side effects, practical issues in obtaining medications, and forgetfulness have been identified as causes of nonadherence.23,24 Additionally, MMF requires close monitoring of renal, liver, and bone marrow function with laboratory work. Patients can have refills canceled if they fail to complete the required laboratory work. This is another potential etiology of nonadherence.

There are direct and indirect methods to measure medication adherence rates, with the latter being far more convenient and practical.25–27 The proportion of days covered (PDC) is the number of days covered by a medication divided by the number of days in a set period. It is calculated using pharmacy refill data and is expressed as a percentage. Medicare and Medicaid use PDC as a metric for patient adherence to medication. One advantage to this method is that it is readily available through many electronic medical record systems and is noninvasive. One of the limitations of PDC is that it only measures whether a patient has enough medication; it does not directly measure whether they correctly administered their medication.28

The authors do not know how many of their patients with LN are nonadherent to their medication regimens. To better understand patient-centered contributing factors, the authors identified patients with LN who were on MMF. Using PDC, nonadherent patients were identified and then surveyed to learn about causes of medication nonadherence. The goal was to identify causes of medication nonadherence in patients with LN on MMF within Kaiser Permanente East Bay Area and design a targeted quality improvement project.

Methods

The Research Determination Committee for the Kaiser Permanente Northern California region has determined this project does not meet the regulatory definition of research involving human participants per 45 CFR 46.102(d).

Using pharmacy refill data, the authors identified patients who: were prescribed MMF between November 30, 2021, and November 30, 2022, had a confirmed LN International Classification of Diseases, 10th Revision, code (M32.14), and had a rheumatologist or nephrologist within the Kaiser Permanente Eastbay service area. The diagnosis of LN was confirmed by chart review of prior biopsies (if available) and clinical documentation by respective nephrologists and rheumatologists. The authors collected patient demographic information, including age, sex, 30-day copay, ethnicity, the requirement of kidney replacement therapy (dialysis), and the PDC for MMF. After identifying patients with diagnosed LN on MMF, the authors separated them into adherent and nonadherent based on their PDC. A PDC of ≥ 80% was considered adherent. The nonadherent patients were identified, and semistructured telephone interviews were conducted. The questions allowed for open-ended answers and assessed patient experiences with their initial diagnosis, chronic illness, medication side effects, obtaining new prescriptions, completing required laboratory work, paying for medication, and taking daily medications. Additional data gathered included employment status, number of children, and the highest level of education.

Written summaries were analyzed, and 6 themes were identified as causes of medication nonadherence (Table 1): 1) failure to complete laboratory work; 2) high medication cost; 3) intentionally missed doses; 4) forgetfulness; 5) medication adverse effect; 6) and pharmacy-related barriers. The authors reviewed the written summaries and then determined if a patient’s reason for low adherence was due to one of the identified themes. Representative quotes were taken from the written summaries. All information was deidentified.

Table 1: Example quotes recorded from patient telephone interviews

Example quotes from interviews	
Laboratory work	“I keep forgetting to do my bloodwork. I have to go in all the time, and I’m still working. I frequently get bruises. I know that it shows important information … it usually takes 15 min."	
Cost of medication	“I have a bad memory, but the costs add up, and I can’t work and have been denied disability.”
“I pay $0 for my medications.”	
Intentionally missed doses	“Since I started medications, they helped a lot. … I’ve become very focused on eating healthy because I want to get off my medications one day. I don’t like to take my medications.”	
Forgetfulness	“Oh man, it’s hard. When work is really busy, I get home, and I lay on the couch. I’m so exhausted that I’ll fall asleep on the couch and forget to take my afternoon meds.”	
Experience with initial diagnosis of lupus nephritis	“I remember being very mad at the initial diagnosis, and I initially did not believe it.”
“Initially I had protein in my urine; it took a while before we realized what it meant. Once I was connected to a nephrologist, I feel like we got things under control.”
“There was a delay in my diagnosis, I felt like my concerns were not initially heard. Once we had a diagnosis, things improved.”	
How has lupus affected your life?	“It means that I have something that people can’t see. My battery charges to 75%; when I don’t feel good, I’m running at 50%. It’s hard for people to understand because I don’t look sick. It hasn’t stopped me from doing what I want to do. I’m a role model for my nieces and nephews, and no matter what life throws at you, you keep going. Lupus doesn’t have me, I have lupus.”	

Results

Among 36 patients with diagnosed LN who were taking MMF (median age was 49 years old; 89% were female), 45% were Asian, 22% Black, 33% Hispanic, and 0% NHW. The median 30-day copay was $3.47. Only 1 patient (3%) required renal replacement therapy (Table 2). Of the total number of patients, 69% were adherent (PDC ≥ 80%), 20% had a PDC ≥ 60% to < 80%; 8% had a PDC ≥ 30% to < 60%, 3% had a PDC of < 30% (Figure 1), and 31% of patients were nonadherent (PDC of < 80%). The median age was 47 years old, 82% were female, and the respective races and ethnicities were 18% Asian, 27% Black, 55% Hispanic, and 0% NHW. Their median 30-day copay was $4.55. The 30-day copay range was $0 to $14.63.

Table 2: Characteristics of patients with lupus nephritis on mycophenolate mofetil

Characteristic	Patients on MMF
(N = 36)	Patient on MMF with PDC < 80%
(N = 11)	Patients on MMF with PDC < 80% who agreed to be interviewed
(N = 7)	
Median age, y	49	47	40	
Female sex, %	89	82	100	
RRT, %	3	0	0	
Race/ethnicity, %
Asian
Black
Hispanic
NHW	45
22
33
0	18
27
55
0	14
43
43
0	
30-d copay range	$0 to $14.63	$0 to $14.63	$0 to $14.63	
Median 30-d copay	$3.47	$4.55	$4.55	
MMF, mycophenolate mofetil ; NHW, Non-Hispanic White; PDC, proportion of days covered; RRT, renal replacement therapy.

Figure 1: Adherence rates for patients with lupus nephritis on mycophenolate mofetil determined using PDC. PDC = proportion of days covered.

Among patients with a PDC of < 80%, 63% agreed to be interviewed. They identified the following causes of medication nonadherence: forgetfulness (57%), incomplete laboratory work (28%), medication cost (14%), and intentionally missed doses (14%; Figure 2). No patients identified medication side effects as a cause, 71% reported no issues obtaining new prescriptions, 86% received their medications via mail, and 28% of patients paid $0 for their medications. Of the patients interviewed, 71% are currently employed, 58% have children, 14% obtained a degree beyond a high school diploma.

Figure 2: Patient-reported causes of medication nonadherence.

Discussion

In the authors’ quality improvement project, patients who were not adherent to their MMF medication cited forgetfulness as a cause of medication nonadherence. Convenient refills and laboratory draws benefit this high-risk population.

Prior studies have shown that medication nonadherence rates for patients with lupus can be as high as 75%.17,20,21 Considering the limitations of the authors’ small sample size, only 31% of patients with LN were nonadherent to MMF medication, and 20% of those nonadherent patients had PDC between 60% and 80%. These patients were viewed as close to the goal of PDC > 80% and potentially easier to coach into improved medication adherence.

Although prior studies have identified cost, medication side effects, forgetfulness, lack of understanding, logistical challenges with refilling prescriptions, and poor communication between practitioners and patients as causes of medication nonadherence, the authors’ results suggest forgetfulness as the most common cause.23,24 Failure to complete laboratory work, medication side effects, affordability, and lack of understanding were still important factors for the authors’ patients but were less commonly cited. Many patients discussed learning the best ways to navigate getting laboratory work done quickly, including which laboratory tests were quickest and how to use the online reservation system to avoid waiting in lines. Multiple patients interviewed were enthusiastic about the online refill system, making statements such as, "The system works great!" or "I have not had any problems with refills."

Although forgetfulness is a well-documented cause of medication nonadherence in the population with LN, it is not entirely understood.24,29 Lack of motivation or complacency, concurrent depression, and cognitive dysfunction due to neuropsychiatric lupus have also been implicated.24,30,31 The phenomenon of complacency is seen in other chronic conditions and is illustrated by this quote about patients with multiple sclerosis: "Patients who have been on therapy for a while and have not experienced any relapses or signs of progression may begin to think that they do not need to self-inject anymore or at least not as regularly as indicated or prescribed.”32 The authors suspect some of their patients in remission experienced complacency and lost motivation to continue their medications daily; this leads to forgetfulness and low medication adherence rates. Further studies should attempt to clarify whether forgetfulness is a surrogate for reduced motivation and complacency and to what degree depression and neuropsychiatric SLE contribute to forgetfulness.

These data only include patients who filled a prescription for MMF; therefore, a patient who was prescribed MMF but never filled the prescription would not be included. This sampling error would lead to an overestimation of the medication adherence rate. Kaiser Permanente Northern California is a highly diverse patient population with Medicaid, Medicare, and employer-based insurance plans. This population’s socioeconomic, educational level, and ethnicities may or may not match that of other studied populations, limiting the comparison of the data to other populations. Only 7 of 11 nonadherent patients agreed to be interviewed. Given the small sample size, these results could be different if the other nonadherent patients had agreed to be interviewed. Lastly, the authors likely have not yet captured a complete data set of all patients with LN on MMF in the Kaiser Permanente East Bay Area due to potential refills not being during the specified period or outside the system.

Additional limitations of the PDC metric exist. PDC objectively measures whether a patient has medication during a set period. It is not proof that they took the medication. PDC can be falsely low due to the "stockpile" effect. During induction therapy, a patient may be on a higher dose of MMF before being deescalated to a lower dose. This results in patients having a surplus of medication and requiring fewer refills, thus artificially lowering their PDC. The authors’ respondents were all in the maintenance phase, so they suspect this did not play a role in their project.

Additionally, the authors educated their practitioners on methods to counsel patients on medication adherence. Using a model piloted at Duke University, the authors trained their practitioners to use EPIC electronic medical record refill data to initiate a conversation with patients about their medication adherence.33 At the practitioners’ discretion, they counsel patients and provide interventions as they see fit. Practitioners were encouraged to approach these conversations with a nonjudgmental and empathic perspective. Statements that validate a patient’s experience, such as, "It is difficult to take all these medications," were encouraged. If cost was an issue, a social work referral could be placed. A medication reminder application or pill box was recommended if forgetfulness was an issue. If the patient’s lack of understanding was the issue, the practitioner was encouraged to educate and counsel the patient. Health literacy has been known to contribute to medication adherence and a next step to address possible disparities would be further evaluation of social determinants of health in this population.

The authors’ preliminary data suggest that convenient refills and convenient laboratory draws benefit their patients. Forgetfulness was identified as a critical driver for medication nonadherence. Contributing factors may be pill fatigue due to having a chronic disease or complacency over time in the subjective assessment of their condition. The authors suggest the following future interventions to address these barriers and maintain open, nonjudgmental dialogue with patients: 1) evaluating and addressing mental health needs, 2) behavioral health education about the disease process and medication adherence, and 3) assistive tools like pill boxes and electronic applications to remind patients to take their medications. In conclusion, this is the first project using patient-centered interviews performed in patients with LN at a large medical center at Kaiser Permanente Northern California to better understand medication nonadherence.

Acknowledgments

The authors acknowledge the patients' valuable contribution of their time and experiences to aide the authors' understanding of medication adherence in lupus nephritis.

Author Contributions: Sijie Zheng, MD, PhD, and Patty Pei-chang Chen, MD, are co-senior authors. Christopher A Macko, MD, Nicole Tran, MD, PhD, Patty Pei-chang Chen, Sijie Zheng, Roger Santos, PharmD, and Nirmala D Ramalingam, MPP, conceived the project and developed the project plan. Roger Santos provided the data. Christopher Macko wrote the first draft of the paper. All authors contributed to the interpretation of the data, critically reviewed and revised the manuscript for intellectual content, and approved the final manuscript for publication.

Conflict of Interest: None declared

Funding: None declared

Data-Sharing Statement: The data that support the findings of this project are not available.
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