Using linked electronic medical record-pharmacy data to examine lupus medication adherence: A retrospective cohort study.

INTRODUCTION: Medication nonadherence is common in systemic lupus erythematosus (SLE) and associated with morbidity and mortality. We explored the reliability of pharmacy data within the electronic medical record (EMR) to examine factors associated with nonadherence to SLE medications. METHODS: We included patients with SLE who were prescribed ≥1 SLE medication for ≥90 days. We compared two datasets of pharmacy fill data, one within the EMR and another from the vendor who obtained this information from pharmacies and prescription benefit managers. Adherence was defined by medication possession ratio (MPR) ≥80%. In addition to MPR for each SLE medication, we evaluated the weighted-average MPR and the proportion of patients adherent to ≥1 SLE medication and to all SLE medications. We used logistic regression to examine factors associated with adherence. RESULTS: Among 181 patients (median age 36, 96% female, 58% Black), 98% were prescribed hydroxychloroquine, 34% azathioprine, 33% mycophenolate, 18% methotrexate, and 7% belimumab. Among 1276 pharmacy records, 74% overlapped between linked EMR-pharmacy data and data obtained directly from the vendor. Only 9% were available from the vendor but not through linked EMR-pharmacy data. The weighted-average MPR was 57%; 45% were adherent to hydroxychloroquine, 46% to ≥1 SLE medication, and 32% to all SLE medications. Older age was associated with adherence in univariable and multivariable analyses. DISCUSSION: Our study showed that obtaining linked EMR-pharmacy data is feasible with minimal missing data and can be leveraged in future adherence research. Younger patients were more likely to be nonadherent and may benefit from targeted intervention.

Impact of preeclampsia on infant and maternal health among women with rheumatic diseases.

OBJECTIVES: We sought to identify the impact of preeclampsia on infant and maternal health among women with rheumatic diseases. METHODS: A retrospective single-center cohort study was conducted to describe pregnancy and infant outcomes among women with systemic lupus erythematosus (SLE) with and without preeclampsia as compared to women with other rheumatic diseases with and without preeclampsia. RESULTS: We identified 263 singleton deliveries born to 226 individual mothers (mean age 31 years, 35% non-Hispanic Black). Overall, 14% of women had preeclampsia; preeclampsia was more common among women with SLE than other rheumatic diseases (27% vs 8%). Women with preeclampsia had a longer hospital stay post-delivery. Infants born to mothers with preeclampsia were delivered an average of 3.3 weeks earlier than those without preeclampsia, were 4 times more likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. The large majority of women with SLE in this cohort were prescribed hydroxychloroquine and aspirin, with no clear association of these medications with preeclampsia. CONCLUSIONS: We found preeclampsia was an important driver of adverse infant and maternal outcomes. While preeclampsia was particularly common among women with SLE in this cohort, the impact of preeclampsia on the infants of all women with rheumatic diseases was similarly severe. In order to improve infant outcomes for women with rheumatic diseases, attention must be paid to preventing, identifying, and managing preeclampsia.

A qualitative study of facilitators of medication adherence in systemic lupus erythematosus: Perspectives from rheumatology providers/staff and patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) disproportionately affects patients from racial and ethnic minority groups. Medication adherence is lower among these patient populations, and nonadherence is associated with worse health outcomes. We aimed to identify factors that enable adherence to immunosuppressive medications among patients with SLE from racial and ethnic minority groups. METHODS: Using a qualitative descriptive study design, we conducted in-depth interviews with purposefully selected (1) patients with SLE from racial and ethnic minority groups who were taking immunosuppressants and (2) lupus providers and staff. We focused on adherence facilitators, asking patients to describe approaches supporting adherence and for overcoming common adherence challenges and providers and staff to describe actions they can take to foster patient adherence. We used applied thematic analysis and categorized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model. RESULTS: We interviewed 12 patients (4 adherent and 8 nonadherent based on medication possession ratio) and 12 providers and staff. Although each patient described a unique set of facilitators, patients most often described social support, physical well-being, reminders, and ability to acquire medications as facilitators. Providers also commonly mentioned reminders and easy medication access as facilitators as well as patient education/communication and empowerment. CONCLUSION: Using an established behavioral change model, we categorized a breadth of adherence facilitators within each domain of the COM-B model while highlighting patients' individual approaches. Our findings suggest that an optimal adherence intervention may require a multi-modal and individually tailored approach including components from each behavioral domain-ensuring medication access (Capability) and utilizing reminders and social support (Opportunity), while coupled with internal motivation through improved communication and empowerment (Motivation).

The Type 1 & 2 systemic lupus erythematosus model: Perspectives of people living with systemic lupus erythematosus.

OBJECTIVE: In the new Type 1 & 2 model for systemic lupus erythematosus (SLE), Type 1 SLE represents classic inflammatory manifestations, such as arthritis, while Type 2 SLE encompasses symptoms such as pain and fatigue where the relationship to inflammation is less clear. The objective of this study was to interview individuals living with SLE to determine the content and face validity of the Type 1 & 2 SLE model. METHODS: We conducted a qualitative study using semi-structured interviews with a purposeful sample of participants who met classification criteria for SLE. Participants were asked to describe their experiences with Type 1 & 2 SLE symptoms and treatments, and they indicated if and how their personal experiences aligned with the Type 1 & 2 SLE model. All interviews were audio-recorded and transcribed; applied thematic analysis identified the most frequent and salient themes. RESULTS: We interviewed 42 participants with SLE. Type 2 SLE symptoms, such as pain and fatigue, were very common, with almost all participants experiencing some Type 2 symptoms at some point during their disease course. Participants described Type 1 SLE symptoms as being acute flares and life-threatening and Type 2 SLE symptoms as "everyday lupus" that affected their daily lives and were a dominant part of their SLE disease experience. Most participants stated they want their rheumatologists to discuss Type 2 symptoms during clinical appointments in order to address their full symptom experience. CONCLUSION: We demonstrated content and face validity of the Type 1 & 2 SLE model with people living with SLE. Participants in our study largely understood the model and felt it accurately reflected their experience living with SLE. Type 2 SLE symptoms are very common in individuals with SLE and impact patients' quality of life. Using the model to address Type 2 SLE symptoms allows the rheumatologist to incorporate the patient's perspective and provide patient-centered care.

The impact of pregnancy planning and medical readiness on reproductive outcomes in women with systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) who get pregnant while SLE is active or while on teratogens have higher risk of poor pregnancy outcomes. The American College of Rheumatology (ACR) Reproductive Health Guidelines recommend women conceive when SLE is well controlled and treated with pregnancy-compatible medications. The Healthy Outcomes in Pregnancy with SLE Through Education of Providers (HOP-STEP) Intervention was created to ascertain pregnancy interest and contraceptive use followed by a personalized pregnancy prevention and/or planning discussion (https://www.LupusPregnancy.org). All study participants were adult females enrolled in a prospective registry who met ACR or SLICC criteria. Women were defined as "not medically ready for pregnancy" if they were currently prescribed a teratogen, had proteinuria ≥500 mg, or had elevated SLE activity according to the physician's global assessment. Two time periods were assessed: 2/2018-12/2019 and 10/2020-4/2021 to evaluate pre- and post-pandemic periods, with some post-pandemic visits taking place via telehealth. The interest in pregnancy was similar between the first time period (17%) and the second time period, whether in-person (18%) or virtual (18%). Pregnancy interest was assessed significantly more frequently during in-person visits (90%) compared to virtual encounters (67%) (p = .02). Contraceptive use was not significantly different during either time period with use of a teratogen or increased SLE activity. Of the 52 women in both time periods who were not medically ready for pregnancy and were not on effective contraception, three women (5.8%) conceived. None of the women who were using moderate or highly effective contraception became pregnant. Pregnancy outcomes were similar between unintended or high-risk and well-timed pregnancies. The HOP-STEP Intervention effectively identified pregnancy interest, giving rheumatologists the opportunity to address patient reproductive goals, optimize disease activity, and adjust medication regimens prior to conception.

The association of lupus nephritis with adverse pregnancy outcomes among women with lupus in North America.

OBJECTIVES: We evaluated the association of lupus nephritis (LN) and adverse pregnancy outcomes in prospective cohorts of pregnant women with SLE (systemic lupus erythematosus). METHODS: We conducted a patient-level pooled analysis of data from three cohorts of pregnant women with SLE. Pooled logistic regression models were used to evaluate the association of LN and adverse pregnancy outcomes. Odds ratios and 95% confidence intervals were calculated using a fixed effect model by enrolling cohort. RESULTS: The pooled cohort included 393 women who received care at clinics in the United States and Canada from 1995 to 2015. There were 144 (37%) women with a history of LN. Compared to women without LN, those with LN had higher odds of fetal loss (OR: 1.90; 95% CI: 1.01, 3.56) and preeclampsia (OR: 2.04; 95% CI: 1.01, 4.13). Among the 31 women with active nephritis (defined as urine protein ≥ 0.5 g/24 h) there was a higher odds of poor pregnancy outcome (OR: 3.08; 95% CI: 1.31, 7.23) and fetal loss (OR: 6.29; 95% CI: 2.52, 15.70) compared to women without LN. CONCLUSIONS: In this pooled cohort of women with SLE, a history of LN was associated with fetal loss and preeclampsia. Active nephritis was associated with poor pregnancy outcome and fetal loss.

The use of patient-reported outcome measures to classify type 1 and 2 systemic lupus erythematosus activity.

OBJECTIVE: We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity. METHODS: Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0-3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification. RESULTS: The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group. CONCLUSIONS: Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.

Low health numeracy is associated with higher disease activity in systemic lupus erythematosus.

OBJECTIVE: Evidence suggests low health literacy is prevalent in the United States and associated with worse clinical outcomes, yet few studies have investigated health literacy in systemic lupus erythematosus (SLE). The objective of this study was to determine the prevalence of low health literacy and numeracy in lupus patients and to examine its association with disease characteristics. METHODS: Patients with SLE were recruited from an academic center clinic. Participants completed in-person assessments of health literacy (Rapid Estimate of Adult Literacy in Medicine, REALM) and numeracy (Numeracy Understanding in Medicine Instrument Shortened Version, S-NUMi). Clinical disease activity measures were obtained, including urine protein to creatinine ratio (UPC), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment (PhGA) scores. RESULTS: Ninety-five SLE patients participated in the study; 13% had low health literacy and 73% had limited health numeracy. Patients with lower health literacy and numeracy were more likely to be Black, have Medicaid insurance, and earn income <$50 K annually. In linear regression models, patients with limited health numeracy had, on average, PhGA scores 0.31 points higher (95% CI: 0.02, 0.60) than patients with adequate numeracy, after adjusting for race and age. No clinical outcomes were associated with health literacy. CONCLUSION: In this exploratory study, we found SLE patients with low numeracy had higher disease activity. Our findings indicate that lower health literacy and numeracy are more common among Black and socioeconomically disadvantaged patients. Additional research will be needed to investigate the impact of health literacy on other outcomes and racial disparities in SLE.

Pregnancy outcomes, fertility, and family planning in women with psoriatic arthritis.

OBJECTIVE: To quantify pregnancy outcomes and the frequency and cause of infertility among women with psoriatic arthritis. METHODS: Women with psoriatic arthritis aged 20-50 years completed a questionnaire about prior pregnancies, infertility, and family planning. Patient-reported pregnancy outcomes were validated by chart review. RESULTS: In 40 women with psoriatic arthritis, 67% of 70 pregnancies were live births. Patient-reported preterm birth and preeclampsia were more common after psoriatic arthritis diagnosis but were significantly over-reported. Most women reported no or mild joint pain during pregnancy and few took medications for psoriatic arthritis. Infertility was reported by 36% of women who were ever pregnant or ever tried to become pregnant, primarily due to polycystic ovary syndrome. CONCLUSION: The patient-reported pregnancy outcomes in this retrospective survey were not supported by chart review, making prospective studies essential to understand the interaction of psoriatic arthritis and pregnancy. Infertility, particularly due to polycystic ovary syndrome, appears to be an important issue in this population.

Rheumatologists' knowledge of contraception, teratogens, and pregnancy risks.

INTRODUCTION: Rheumatologists are essential partners in planning and managing pregnancies in women with lupus. Whether they know the essentials of contraceptive and medical treatment in pregnancy, however, is unknown. METHOD: Anonymous in-lecture surveys were completed by 270 rheumatologists to assess knowledge of contraceptive effectiveness, emergency contraception, medication teratogenicity, and lupus pregnancy risk assessment. RESULTS: Rheumatologists knew the high effectiveness of the intrauterine device, but over-estimated the effectiveness of injectable medroxyprogesterone and condoms. Almost all identified methotrexate as a teratogen, but only 69% identified cyclophosphamide and 37% mycophenolate. Most rheumatologists knew that lupus activity in pregnancy is the main predictor of pregnancy outcomes, but underestimated the risks of hypertension and race. CONCLUSION: To improve lupus pregnancy planning and management, rheumatologists would benefit from improved knowledge about contraceptive effectiveness, teratogens, and the risks from non-lupus factors for pregnancy complications.

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study.

BACKGROUND: Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. METHODS: CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. RESULTS: 19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. CONCLUSION: When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc--free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. TRIAL REGISTRATION NUMBER: NCT02154425; Results.

The use of anti-TNFα medications for rheumatologic disease in pregnancy.

Anti-TNFα medications have led to vast improvements in the treatment of inflammatory conditions, including rheumatoid arthritis and Crohn's disease. As these diseases often afflict women in their reproductive years, the safety of these drugs during pregnancy is an important issue. Prospectively collected data thus far appear to be reassuring; however an analysis of the FDA-reported anomalies has raised some questions. It appears that significant levels of these drugs cross the placenta as the pregnancy nears term, but little is passed through breast milk. Prior to using these medications during pregnancy, the risks and benefits of these drugs, other treatment options, and the ongoing inflammatory condition all must be carefully weighed by both doctor and patient.