Objectives: The aim of this thesis was to evaluate the clinical use of rituximab (RTX) in rheumatoid arthritis (RA) patients treated in routine clinical practice in the UK, taking account of the previous therapies (anti-tumour necrosis factor (anti-TNF) therapies).Methods: The analysis involved RA patients registered with the British Society for Rheumatology Biologics Register. Kaplan-Meier survival analysis was used to study the persistence with anti-TNF therapies. Drug persistence was compared across the anti-TNF therapies and according to the most common concomitant non-biological disease modifying anti-rheumatic drugs (nbDMARDs) for up to five years. Adjusted multivariate Cox proportional hazard models were used to compare drug persistence across the subgroups. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical effectiveness of RTX while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients six months after starting RTX. Logistic regression was used to compare EULAR response and achieving a minimal clinically important difference (MCID) in HAQ (at least 0.22) between patients who started RTX and those who switched to a second alternative anti-TNF after failing a first anti-TNF therapy. Multivariate regression analyses were used to identify factors associated with the clinical effectiveness and the improvements in physical function six months after starting RTX. The models included baseline demographics, disease characteristics, baseline quality of life and previous drug history. Results: Among 10,396 RA patients receiving their first anti-TNF therapy, five-year drug persistence (95% CI) was 42% (41%: 43%). Infliximab was the most likely discontinued anti-TNF therapy. Compared to methotrexate (MTX), patients receiving no nbDMARD, leflunomide or sulfasalazine were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other nbDMARDs showed superior persistence with their anti-TNF therapy. After failing the first anti-TNF therapy, patients who switched to RTX were significantly more likely to achieve EULAR response and MCID in HAQ; odds ratio (95% CI) 1.31 (1.02: 1.69) and 1.49 (1.07: 2.08) respectively compared to those who switched to an alternative anti-TNF therapy. In a cohort of 646 RA patients who started RTX, the mean DAS28 scores significantly improved six months after starting RTX with mean (95% CI) change of -1.42 (-1.53: -1.30). 17% of the patients achieved a good EULAR response and 43% achieved a moderate response. Higher baseline DAS28 score and positive rheumatoid factor (RF) status were significantly associated with a decrease in disease activity, while females and patients with higher baseline HAQ score were less likely to respond to RTX. In a cohort of 484 patients receiving RTX, the mean HAQ scores significantly improved by -0.12 (-0.16: -0.09) units. High baseline HAQ score was significantly associated with six months improvement in HAQ. Older patients, females, current smokers and patients receiving concurrent steroids were less likely to show an improvement in their HAQ scores. Conclusions: Compared to MTX, concomitant use of two or three nbDMARDs combinations including MTX with anti-TNF therapies resulted in better persistence with the anti-TNF therapies. After failing the first anti-TNF therapy, starting RTX may be of more benefit than switching to an alternative anti-TNF therapy. RTX has proven to be effective in improving both the clinical and patients' reported outcomes in routine clinical practice in the UK. Response to RTX was influenced by baseline DAS28, RF status, baseline HAQ, age, gender, smoking, and concurrent use of steroids.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22644号 / 医博第4627号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 秀一, 教授 古川 壽亮, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

We have developed a solid-phase radioimmunoassay capable of detecting nanogram quantities of human IgA rheumatoid factor (RF) in biological fluids. Human IgM RF, IgG RF, IgG, IgA, IgM and whole serum did not significantly interfere with the IgA RF assay. Patients with sero-positive rheumatoid arthritis (RA) had significantly higher concentrations of IgA RF than sero-negative RA patients or healthy adult controls. Concentrations of IgA RF in paired sera and synovial fluids from sero-positive RA patients were comparable. Levels of IgA RF demonstrated a moderately good correlation with levels of IgM RF in sero-positive RA sera (r = 0.673). However, the ratio of IgA RF concentration to IgM RF concentration in sero-positive RA sera varied widely.

Thesis (M.S.)--Boston University

published_or_final_version / Community Medicine / Master / Master of Public Health

Thesis--University of Michigan. / Microfilm copy of typewritten ms. Positive. Collation of the original: vi, 168 l. mounted illus. (part col.) tables. Bibliography: leaves 160-168.

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

This study investigates the psychosocial aspects of rheumatoid arthritis (RA),a chronic debilitating disease. It explores the quality of life in a low socio-economic group of clinic-based adult RA patients. The aims of the study were as follows: (1) to assess the impact of both socio-demographic and psychosocial factors on RA health outcome, (2) to develop a multivariate, predictive model for RA, and (3) to assess the moderating role (or stress-reducing function) of psychosocial factors between the objective experience of RA and the subjective experience of RA. A sample of 186 RA patients with a mean age of 49.51 years and a mean duration of RA of 10.80 years were subjected to a series of selfadministering questionnaires to assess their subjective experience of the disease. Coping, social support, causal attribution, cognitive illness representation, pain and functional status were assessed. The objective experience of RA was based on those health status measures that included the following: firstly, ESR levels (a laboratory measure), and secondly, class (classified level of disability) and joint status (severity of joint inflammation) which were assessed and recorded by the rheumatologist. The data obtained were subjected to a systematic statistical analysis to assess the following: (1) the relationships between the socio-demographic factors, psychosocial factors and factors representing RA health outcome using correlational analysis (Pearson r), (2) the value of socio-demograhic and psychosocial factors in predicting subjective and objective RA health outcomes using step-wise hierarchical multivariate regression analysis, and (3) the moderating or stress-reducing effect of psychosocial factors between the objective and subjective health status measures using moderated regression analysis. Findings revealed that psychological factors, especially coping, were more significant predictors than socio demographic factors of RA health outcome (quality of life of RA individuals). Furthermore, the psychosocial factors coping, network social support, helplessness and causal attribution were found to play a moderating role in RA health outcome. The results of the study confirm both the health-sustaining and the stress-reducing function of psychological factors. Theoretically this study is located within the stress and coping paradigm of Lazarus and Folkman (1984). / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 2002.

Thesis (Ph. D.)--Indiana University, 2006. / Includes bibliographical references (leaves 116-132).

Thesis (Ph. D.)--Indiana University, 2006. / Includes bibliographical references (leaves 116-132). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.