Thesis (M.P.H.)--University of Hong Kong, 2006.

Thesis (M. P. H.)--University of Hong Kong, 2006. / Also available in print.

Thesis (Ph. D.)--University of Minnesota, 1999. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 80-96).

Thesis (Ph. D.)--University of Minnesota, 1999. / Includes bibliographical references.

Biological disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of Rheumatoid Arthritis, particularly TNF-α inhibitors, have been shown to improve patient outcome by slowing or halting radiographic damage. However, similar to most immunemodulators, there is an increased risk of infections co-incident with Tumour necrosis factor (TNF)-α inhibitor use, particularly the risk of activated latent tuberculosis infection (LTBI). Therefore, local and international guidelines recommend pre-screening for tuberculosis (TB) prior to the initiation of TNF-α therapy in rheumatoid arthritis (RA) patients. Also of critical importance in South Africa is the need for clinicians to be aware of environmental risk factors such as TB being highly endemic. Thus, a qualitative analysis was performed to investigate rheumatologists’ perceptions of TB co-incident with TNF-α inhibitors. Method: Physicians (n=18) practising rheumatology in the private and public healthcare sectors in Gauteng were interviewed to obtain their perceptions and attitudes related to TB co-incident with TNF-α inhibitor use. Interviews were audio-recorded and the transcripts analysed using thematic content analysis. Results: The determinants of health equity: Affordability, accessibility and availability of medicines (specifically TNF-α inhibitors) was reported to be different for the public care versus the private care patient. The high cost of TNF-α inhibitors warranted funding predominantly by the private medical schemes. A higher occurrence of latent TB infection was reported by physicians practising in the public or combined practice compared to the occurrence of LTBI in the private sector (21.4%versus 1.5%). The majority of study participants advocated pre-screening of TB, prior to the initiation of TNF-α inhibitors, in RA. However, it was suggested that because of the high occurrence of LTBI in the public sector, Isoniazid preventative therapy (IPT) should be compulsory, irrespective of the patient’s TB status, for the duration of TNF-α therapy. Most study participants supported local South African Rheumatism and Arthritis Association (SARAA) guideline recommendation to re-screen for TB by chest x-ray (CXR), every 6 months. However, the value of re-screening using diagnostic tools, purified protein derivative (PPD) skin test or interferon-gamma release assays (IGRAs) was queried due to the possibility of false readings. The occurrence of associated active TB in RA patients on TNF-α inhibitors was reported to be 0.07% in the private or combined practice versus 3.00% in the public sector. Forty percent of TB cases were reported to be extra-pulmonary. Despite active vigilance, some physicians reported that active TB month occurred months after the cessation of TNF-α inhibitor therapy. [Similar findings were observed from the British Society for Rheumatology Biologics Register (BSRBR)]. The majority of patients that developed TB co-incident with TNF-α inhibitors were treated successfully with TB chemotherapy. Only 1 of 12 patients died of extra-pulmonary TB, following compassionate use of infliximab in public care. Conclusion: Physicians practising rheumatology in Gauteng were of the opinion that there is a TB risk associated with the use of TNF-α inhibitors for the management of rheumatoid arthritis, as South Africa is a TB endemic country. Most acknowledged that these biological DMARDs were efficacious in slowing or halting radiographic progression in rheumatoid arthritis, but emphasised the need to take steps to prevent TB reactivation in the immuno - compromised RA patients and to remain overtly vigilant for active TB. In clinical practice, physicians mentioned that the monitoring and management of TB associated with TNF-α inhibitors appears to follow the socio-economic status of the RA patient and that distinct recommendations should be made for the public healthcare as well as the private healthcare sectors. Different opinions emanated from different physicians relating to the adequacy of local SARAA guidelines for the prevention of TB associated with TNF-α inhibitors. Some physicians mentioned that local guidelines were sufficient, whilst other physicians mentioned that the diagnostic tools were inadequate in the South African setting and that additional precautions should be taken in the form of IPT for the full duration of TNF-α therapy for all candidates, irrespective of TB status determined during pre-screening. As the science of biological DMARDs evolves with the rapid development of new medicinal therapies, physicians showed a preference to consider alternative non TNF-α biological DMARDs that had a lower risk of associated TB, specifically in high-risk RA patients. Physicians’ overall perception of the management of RA with TNF-α inhibitor therapy was that the risk-benefit assessment of these interventions, as well as patient preference and economic considerations should be taken into account.

Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.

published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

Objectives: To identify the predictors of switching from the first biologic to a second biologic in rheumatoid arthritis (RA) patients newly initiated on biologic treatments. Methods: Adult RA patients (18-64 years old) initiated on adalimumab, etanercept, infliximab, certolizumab, golimumab, abatacept, rituximab, tocilizumab, or anakinra between 2009 and 2011 were identified using a commercial claims database. Switching patterns were examined within one year after biologic initiation using descriptive statistics. Health care resource utilization (HCRU) variables (the number of 30-day supplies for steroid and DMARDs, and the claim counts for RA-related outpatient visits, radiographic, laboratory, intra-articular injections, rehabilitation, and surgical procedures) were assessed within one year prior to the switch date for switchers or the end of the study period for non-switchers. Pairwise comparisons of patient characteristics and HCRU variables were conducted using t-tests, Mann-Whitney U tests, and Chi-squared tests. Multiple logistic regressions were used to identify HCRU predictors of switching. Results: A total of 12,370 patients were included in the analysis. The switch rate within one year after biologic initiation was 18.4%, and the median time to switch was 181 days. More females switched compared to males (19.2% vs. 15.9%, p<.001). Switch rates were also higher in patients started on anti-TNFs compared to non-anti-TNFs (19.2% vs. 12.0%, p<.001). Furthermore, switch rates were highest in patients started on golimumab (21.0%) and were lowest in patients started on rituximab (4.8%). Overall, switchers had significantly higher rates and quantities of RA-related HCRU than non-switchers, except in the use of surgical procedures. Logistic regression models revealed that all the HCRU variables were significant predictors of switching, and patients on infliximab, abatacept, tocilizumab, and rituximab had significantly lower odds of switching than patients on etanercept. Combination therapy with DMARDs was also significantly associated with lower odds of switching. Conclusion: Switching of biologics is common in RA patients initiated on biologic therapy. There are marked differences in demographic characteristics and HCRU patterns between switchers and non-switchers. This study demonstrates that patterns of RA-related HCRU can be used to predict switching and thus can potentially serve as useful measures of treatment ineffectiveness. / text