Objective: This study prospectively investigated disease activity, functional disability and health-related quality of life (HRQoL ) in South Africans with early RA, and sought predictors of clinical response at 12 months to traditional disease modifying anti-rheumatic drugs (DMARD) treatment. In addition, the relationships between disease activity, circulating cytokines, the presence of auto-antibodies, the shared epitope (SE), and rheumatoid nodules (RN) were explored. Methods: A cohort of 171 patients with early (≤ 2 years) RA who were DMARD-naïve at inception were prospectively assessed for response to DMARDs over a 12-month period using the simplified disease activity index (SDAI), the Health Assessment Questionnaire-disability index (HAQ-DI) and the Short Form-36 (SF-36). At inception, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (aCCP) were measured and genomic DNA was analysed using high-resolution PCR typing of the HLA-DR1 allele. Circulating cytokines and growth factors were measured using the Bio-Plex® suspension array system. Results: The 171 patients (140 females) at baseline had a mean age of 47 years, mean symptom duration of 12 months and had severe disease with a mean SDAI of 39, HAQ of 1.7, and globally low SF-36 scores. In the 134 patients seen at 12 months, despite significant improvements, only 28% achieved low disease activity, and 69% still had substantial functional disability (HAQ-DI >0.5), and 66% had suboptimal mental health (SF-36 mental composite score <66.6). Baseline predictors of poor outcomes included unemployment, low level of schooling, female sex, high HAQ-DI and pain scores, and a low haemoglobin level. The 6-months SDAI was better than the baseline SDAI in predicting the 12-month SDAI. The sensitivity and specificity of the aCCP test was 83%, and 85%, and the best specificity seen when both RF and aCCP were positive (95%). SE alleles were found in 92% of patients, and were strongly associated with aCCP, with disease activity and with proinflammatory cytokines. Circulating cytokines in RA reflect a multifaceted increase in immune reactivity with strong correlations between these cytokines, and auto-antibodies, in particular in the subgroup of patients with high disease activity. Subcutaneous RN were seen in 23% of patients, and were associated with more severe joint disease, and significantly higher levels of Th1 and macrophage derived cytokines, with significantly higher vascular endothelial growth factor levels. Conclusions: In this, the first prospective study of RA in sub-Saharan Africa, patients had severe RA, with a high disease burden at baseline and a high proportion carrying the SE allele, aCCP and rheumatoid nodules, with a multifaceted increase in circulating pro-inflammatory cytokines and growth factors. A large proportion of early RA patients have ongoing disease activity, substantial functional disability and suboptimal mental health despite 12 months of DMARD therapy. These findings, together with the high number of patients lost to follow-up, underscore the need for better disease control including an aggressive tight control strategy, and biologic therapy, and for patient- centred rehabilitation programmes with close links to psycho-social services.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Supervisor: David L. Kahn. Vita. Includes bibliographical references. Also available from UMI.

Diss. (sammanfattning) Umeå : Univ., 2006. / Härtill 4 uppsatser.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis--Åbo Akademi.

Inaug.-Diss.--Basel. / At head of title: Aus der Medizinischen Universitäts-Poliklinik Basel. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Inaug.-Diss.--Basel. / At head of title: Aus der Medizinischen Universitäts-Poliklinik Basel. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1942. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 74).

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