Longitudinal non-adherence predicts treatment escalation in paediatric ulcerative colitis

Abstract

Background: Medication non-adherence in paediatric ulcerative colitis (UC) has been associated with negative health outcomes including flares in disease activity. However, no studies to date have examined longitudinal adherence to maintenance medication in a prospective controlled trial.

Aims: To determine whether objectively measured adherence to standardised mesalazine (mesalamine) therapy over time was related to remission at 52 weeks and the need for treatment escalation in newly diagnosed paediatric patients with UC METHODS: PROTECT (NCT01536535) was a prospective, inception cohort, multi-site study of paediatric patients aged 4-17 years with newly diagnosed UC followed for 52 weeks. Patients received standardised mesalazine, with pre-established criteria for escalation to thiopurines or anti-TNFα inhibitors. Patients used pill bottles with electronic caps to monitor mesalazine adherence. We tested whether longitudinal adherence to mesalazine predicted steroid-free remission at week 52 (i.e. quiescent disease on mesalazine alone with no corticosteroids ≥4 weeks prior) and need for treatment escalation (i.e. introduction of immunomodulators, calcineurin-inhibitors or anti-TNFα inhibitors).

Results: Among 268 patients, average mesalazine adherence trajectories did not predict week 52 steroid-free remission. Declining adherence over time strongly predicted treatment escalation (β = -.037, P = .001). By month 6, adherence rate ≤85.7% was associated with treatment escalation.

Conclusions: Non-adherence may have affected therapeutic efficacy of standardised mesalazine, thereby contributing to need for treatment escalation. Routine adherence monitoring for at least 6 months following treatment initiation and addressing adherence difficulties early in the disease course are recommended.

Keywords: adherence trajectories; children; clinical remission; paediatric; treatment escalation; ulcerative colitis.

FIGURE 1

Observed monthly average mesalazine adherence rates with 95% confidence intervals for Week 52 ‘Steroid-Free Remission’ (n = 122) and ‘No Steroid-Free Remission’ (n = 146) groups

FIGURE 2

Observed monthly average mesalazine adherence rates with 95% confidence intervals for ‘No Treatment Escalation’ (n = 164) and ‘Treatment Escalation’ (n = 104) groups

FIGURE 3

Model-based mesalazine adherence trajectories with 95% confidence intervals for ‘No Treatment Escalation’ and ‘Treatment Escalation’ groups. Trajectories were calculated for each group using trajectory standard error and slope data from model of treatment escalation predicting adherence. By month 6, the 95% CIs for the two groups no longer overlapped, indicating that an adherence percentage at or below 85.7% (upper bound 95% CI for ‘Treatment Escalation’ group) was indicative of need for treatment escalation

FIGURE 4

Model-based adherence to mesalazine trajectories with 95% confidence intervals for participants with treatment escalation (n = 103). Trajectories were calculated for each group using trajectory standard error and slope data from model of rescue intervention type predicting adherence. The green line represents patients who were prescribed Anti-TNF as first rescue medication (n = 31) and the blue line shows patients who were prescribed an immunomodulator as first rescue medication (n = 72). Only one patient was prescribed a calcineurin inhibitor for first rescue medication, and no patients received colectomy as first rescue intervention, therefore these groups were not modelled