Pharmaco-epidemiological assessment of the clinical use of biologic therapies in the management of rheumatoid arthritis

UoM administered thesis: Phd

  • Authors:
  • Moetaza Soliman


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.


Original languageEnglish
Awarding Institution
Award date1 Aug 2012