Dose flexibility Clause Samples

Dose flexibility. The original dosing schedule for golimumab was restrictive and included no protocolised or licensed escalation. However, in some published series, dose escalation has been described and there are data that it can recapture response. Taxonera et al. (2017) reported 28 patients who were dose escalated either by increasing the dose from 50 to 100 mg 4-weekly (90.3%), from 100 to 200 mg 4-weekly (3.2%) or to 100 mg every 2 weeks (6.4%). A significant number (71%) of patients were able to recapture response with this strategy (Taxonera et al., 2017). In Ireland presently, the randomised multi-centred GOAL-ARC study is progressively dose-escalating patients (up to 200 mg 4-weekly) based on FC and drug levels (Sheridan et al., 2018). The results of this study should offer evidence regarding how best to modify maintenance dosing to optimise outcomes. On the basis of emerging evidence, there has recently been a change in the golimumab induction dosing approved by the EMA. This allows patients with body weight <80 kg who have an inadequate response to induction dosing at weeks 0 and 2, to continue with 100 mg at week 6 and every 4 weeks thereafter, instead of 50mg. The change took into account the type of data generated by ▇▇▇▇▇▇ et al. (2019) in their post-hoc analysis of data from PURSUIT-M. They found that early use of the 100 mg maintenance dose led to achievement of clinical response at week 14 in 28% of patients who had failed to respond to golimumab at week 6. Early non-responders <80 kg who received the 100 mg maintenance dose were also found to have achieved adequate golimumab concentrations (▇▇▇▇▇▇ et al., 2019). The overall aim of this thesis is to provide new insights into the potential role of TDM in maximising the benefit that golimumab can provide for patients with UC. The first steps in this process are to consider the range of available techniques used to measure golimumab and anti-golimumab antibody concentrations, and to evaluate the operating characteristics of a commercially available assay through an assay validation/verification program. The following chapter will address the real-world effectiveness of golimumab through a retrospective, observational study and will provide information regarding optimisation strategies such as empirical dose escalation. Finally, by designing and performing a prospective, phase IV clinical trial we aim to gain deeper insights into important pharmacokinetic aspects of golimumabs use, including therapeutic thresh...