Interpreting hydroxychloroquine blood levels for medication non-adherence: a pharmacokinetic study.

OBJECTIVE: Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients. METHODS: We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses. RESULTS: For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2-4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements. CONCLUSIONS: We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy.

Development and psychometric evaluation of a physician global assessment for type 2 systemic lupus erythematosus symptoms.

OBJECTIVE: Manifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment ('Type 2 PGA'). METHODS AND ANALYSIS: The Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry. RESULTS: There was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSION: The Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider's attention to certain symptoms not well represented in conventional measures of disease activity.

Association of Health Literacy and Numeracy With Lupus Knowledge and the Creation of the Lupus Knowledge Assessment Test.

OBJECTIVE: Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with SLE knowledge. METHODS: Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign [NVS]; n = 96) and numeracy (Numeracy Understanding in Medicine Instrument, Short Version [S-NUMI]; n = 85). They also completed the Lupus Knowledge Assessment Test (LKAT), which consists of 4 questions assessing SLE knowledge that were determined through consensus expert opinion for their wide applicability and importance related to self-management of the disease. Descriptive statistics and multivariable logistic regression modeling were used to analyze the results. RESULTS: In our SLE cohort (n = 125), 33% (32/96) had limited health literacy and 76% (65/85) had limited numeracy. The majority correctly identified that hydroxychloroquine prevented SLE flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was > 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education. CONCLUSION: Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve patients' understanding of proteinuria and investigate whether literacy-sensitive education can improve care.