Purpose: To describe the experience of managing relapsing-remitting multiple sclerosis among adult women users of injectable disease modifying drugs, including day-to-day management, medication beliefs, and health care provider influence. Rationale/Significance of the study:Approximately 85% of the 400,000 Americans with multiple sclerosis have relapsing-remitting multiple sclerosis (RRMS), characterized by unpredictable relapses and partial or full remissions of neurological symptoms. Untreated, RRMS may progress to permanent, irreversible disability and decreased quality of life. Current guidelines recommend immediate and sustained treatment with injectable disease modifying drugs (DMDs). However, despite pronounced modest benefits, approximately 30%-62% of patients are not undergoing DMD therapy. A small number of quantitative studies have identified factors that predict adherence to injectable DMDs. However, little is known about injectable DMDs from patients’ perspectives. It is important to develop an understanding of the experience of managing RRMS among adult users of injectable DMDs in order for health care providers to provide ongoing education, counseling, and support. Organizing Framework:The framework, Beliefs About Medicines, was used to guide the study. Design: Qualitative descriptive design. Setting: Data were collected from adult women with RRMS who received care from an MS clinic, a neurology practice, and through snowball sampling. Sample: Purposive and theoretical sampling was used to recruit 32 women with RRMS. Maximum variation sampling ensured the appropriate breadth and depth of experiences. Women currently undergoing injectable DMD therapy (n = 25), as well as women who either discontinued (n = 6), or never used (n = 1) injectable DMDs were interviewed. Methods: A qualitative descriptive design was utilized. Verification occurred through trustworthiness of data, including rich, thick description from qualitative interviews; field notes and memoing; and member checks. Simultaneous data collection, analysis, and interpretation facilitated interview revision in order to elicit or expand emerging themes. Content analysis inductively derived themes and patterns within and across categories. Participant quotes substantiated particular themes. Confirmability of the data analysis process was undertaken in consultation with the research advisor. Implications: Findings elucidated adult women’s subjective experiences concerning management of RRMS among users of DMDs, including day-to-day management, medication beliefs, and health care provider influence. Results from this study can be used to educate, counsel, and support women in the management of RRMS.

Remarkable progress has been made in the development of effective treatments for patients with rheumatoid arthritis (RA). To ensure that a patient is optimally responding to treatment, consistent monitoring of disease activity is recommended. Established composite and individual disease activity measures often cannot be computed due to missing laboratory values. Simplified measures that can be calculated without a lab value have been developed and previous studies have validated these new measures, yet differences in their performance compared with established measures remain. Therefore, the goal of my doctoral research was to examine and evaluate disease activity and composite measures to facilitate monitoring of response in clinical care settings and inclusion of patients with missing laboratory values in epidemiological research. In the first study, the validity of two composite measures, the Clinical Disease Activity Index (CDAI) and the Disease Activity Score with 28 joint count (DAS28) was examined and both were significantly associated with a rheumatologist’s decision to change therapy (CDAI OR=1.58; 95% CI: 1.42, 1.76) (DAS28 OR=1.34; 95% CI 1.27,1.56). However, further evaluation using receiver operating characteristic (ROC) analysis found that they were not strong predictors of physician decisions to change therapy (AUC=0.75, 0.76, respectively). Thus, they should not be used to guide treatment decisions in the clinic. Two measures of disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often not measured and impede the computation of composite measures of disease activity. In the second study, significant factors which may predict the measurement of the ESR and CRP were identified and included physician and clinical variables but no quantitative disease activity measures. Thus the suitability of the ESR and CRP as measures of disease activity is suspect. In the final study, I created a new composite measure, the modified disease activity score with 28 joint count (mDAS28), by replacing the laboratory value in the DAS28. The mDAS28 was then validated by comparing its performance with the DAS28. The measures were strongly correlated (r=0.87), and strong agreement was found between the two measures when categorizing patients to levels of disease activity (ĸ=0.77) and treatment response (ĸ=0.73). Therefore, the mDAS28 could be used in place of the DAS28 when laboratory values needed to compute the DAS28 are missing. In summary, I found that the CDAI and DAS28 were not strong predictors of the rheumatologist’s decision to change therapy. I also found that the variability in the measurement of ESR and CRP was not associated with disease activity. I was able to modify the DAS28 by replacing the laboratory measure and create a new simplified measure, the mDAS28. I also validated the mDAS28 for use in the clinic and in epidemiological research when the DAS28 is unavailable.

Depression is a common comorbidity in rheumatoid arthritis (RA), yet it may not be adequately recognized during routine clinical care. RA symptoms may confer a risk for depression, and vice versa; depression may affect RA disease activity and response to treatment. The study aims were to compare patient- and physician-reported depression measures, evaluate the temporal bi-directional association between RA disease activity and depressive symptomology, and assess depression as a moderator of RA treatment. Patients were identified using a national RA registry sample (Consortium of Rheumatology Researchers of North America; CORRONA). Depression prevalence and incidence rates were estimated, and concordance and disagreement using measures reported separately by patients and physicians, as well as baseline cross-sectional associations between RA disease and a history of depression. A survival analysis was conducted to temporally predict the incident onset of self-reported depressive symptoms using the different metrics of RA disease activity. Also, mixed effects models were used to assess prospective changes in RA disease activity by prevalent and incident depressive symptom status. Lastly, logistic regression models compared the likelihood of clinical response to RA treatment during follow-up in those with and without depression when starting biologic disease modifying anti-rheumatic drug (DMARD) therapy. Patient-reported depression rates were much higher and significantly different from physician based comorbidity estimates. Patient and physician RA disease activity measures were associated with an increased risk for depression onset, but not laboratory-reported serum biomarkers. Similarly, depression was temporally associated with significantly slower rates of decline regarding every patient-reported disease activity measure, some physician-reported metrics, but not acute phase reactants. Moreover, there was a significantly lower probability of achieving clinical remission among those with depression on a biologic DMARD after 6 months and an analogous effect at 12-months that was slightly lower in magnitude, which did not reach statistical significance. Rheumatologists under-reported the occurrence of prevalent and incident depressive symptoms, and thus are likely unaware of its presence in their RA patients. Further, the results suggest the bi-directional effects between these conditions are related to the cognitive and behavioral aspects of depression and their interactions with disease activity, rather than shared immunological mechanisms in the context of cell-mediated immunity. When also considering the impact on clinical response to biologic DMARDS, the findings collectively imply that rheumatologists must address any challenges due to depression to provide the best care to their patients.