4. Discussion
filgotinib, UC
DISEASE, REMISSION, DISEASE COURSE
This study assessed the effects of treatment with filgotinib on generic and disease-specific HRQoL, and work productivity in patients with UC in the SELECTION trial. Moreover, to examine the effect of filgotinib at the patient level, we developed and evaluated a four-component composite endpoint, CDC. Treatment with filgotinib 200 mg resulted in improvements in generic and disease-specific HRQoL in the short term [10 weeks] among both biologic-naïve and biologic-experienced patients, with improvements maintained during long-term treatment [58 weeks]. In addition, filgotinib 200 mg treatment was effective in restoring patients’ HRQoL as measured by SF-36 scores to that of the general population after 10 weeks of treatment.Patients consider the ability to improve HRQoL to be among the most important attributes of a UC treatment.Restoration of HRQoL is now among the long-term treatment targets recommended for UC.Treatment differences in HRQoL improvements at week 10 were numerically larger in biologic-experienced than biologic-naïve patients, despite the former group having a lower response rate [53.1% and 66.5% of biologic-experienced and biologic-naïve filgotinib 200 mg-treated patients achieved an MCS response at week 10, respectivelyTo assess the benefits of filgotinib 200 mg at the patient level, we combined endpoints that are treatment targets specified by the STRIDE-II guidelines,Limitations of these analyses include that HRQoL measures were assessed at only two time points. Future studies could assess individual patient trajectories using multiple endpoint data at various time points [from the beginning of treatment through to CDC], in order to evaluate disease burden and fluctuations over time, and to determine early indicators of a positive/negative disease course. A further limitation was that only responders entered the Maintenance Study, owing to the re-randomization trial design. This introduces bias due to the exclusion of non-responders. Nevertheless, this was not considered a major issue, as the purpose of the maintenance phase was to evaluate the perpetuation of previously identified therapeutic benefit arising from the induction phase. It is also worth noting that for the group who received induction filgotinib and maintenance placebo, as noted above, it cannot be ruled out that priming with filgotinib impacted the disease trajectory during maintenance when filgotinib treatment ceased. However, if anything this is likely to favour an underestimation of the benefits of filgotinib. In addition, this is a study design that is frequently employed in UC trials as it allows for evaluation of different treatment durations whilst minimizing the time that any individual patients spend on the placebo. This is important as withholding of favourable care would present ethical issues.Analyses evaluating the composite endpoint were exploratory and require formal external validation, for example reliability testing. This is particularly true considering the response to filgotinib of inflammatory biomarkers. These are well-established indicators of active disease, as well as being the least invasive of all the objective endpoints, and the lack of concordance of their profiles with other disease markers warrants further investigation. Alternatively, our data could suggest the threshold for inflammatory biomarker remission could be made less stringent, given that clinically significant improvements to HRQoL and endoscopic improvement were achieved in this study without the criterion for inflammatory biomarker remission being met. Nevertheless, it could be speculated that assessment of multiple established UC outcomes within a composite endpoint may be valuable for clinicians managing patients with UC, as treatment shifts towards a more personalized and patient-centred approach.