Improved functionality, health related quality of life and decreased burden of disease in patients with ADHD treated with OROS® MPH: is treatment response different between children and adolescents?

Abstract

Background: To compare clinical and health-related quality of life (HRQoL) outcomes between children and adolescents with ADHD treated with OROS® MPH, using data from two large similarly-designed multicenter, prospective, open-label, single-arm, non-interventional studies.

Methods: Pooled analysis (42603ATT4037, 42603 - ATT - 4001) including patients (6 to 18 years) with a confirmed diagnosis of ADHD. Patients were treated with OROS® MPH for 12 weeks; ADHD symptoms, functioning, HRQoL, safety and tolerability parameters were assessed.

Results: 822 patients (583 children [6-12 years], 239 adolescents [13-18 years]) were included in the pooled analysis. Mean daily OROS® MPH starting doses in the child and adolescent subgroups were 29.0 ± 11.7 and 37.6 ± 15.6 mg, respectively (p < 0.001). At study end (week 12), the overall mean daily dose was 35.5 ± 14.0 mg, with children and adolescents receiving 32.8 ± 12.7 and 42.0 ± 15.1 mg/day, respectively (p < 0.001). Significant (p < 0.0001: overall population, children, adolescents) symptomatic, functional and HRQoL improvements were observed from baseline to study end using the Conners' Parents Rating Scale (overall: 29.2 ± 10.7 [baseline] to 19.3 ± 11.3 [endpoint]), Children's Global Assessment Scale (overall: 58.5 ± 14.5 [baseline] to 69.6 ± 16.1 [endpoint]), and ILC-LQ0-28. At week 12, between-age group differences were seen in the individual ILC-LQ0-28 parameters: school performance (p = 0.001 [parents' assessment], p = 0.032 [childrens' assessment]), global QoL (p = 0.012 [parents']) and interests and hobbies (p = 0.023 [childrens']). Treating physician's planned continued use of OROS® MPH in 76.9%, 86.0% and 79.3% of children, adolescents and the total population, respectively, at study end (p = 0.029 between-age subgroups). 195 of 822 patients (23.7%) experienced at least one treatment-emergent adverse event; most commonly reported AEs in the total group (≥4%) were insomnia (7.2%), anorexia (4.3%) and involuntary muscle contractions (4.1%). No clinically relevant changes in body weight or vital signs were observed.

Conclusions: Clinically relevant differences between children and adolescents with ADHD are present. Adolescents appeared to have a lower health related quality of life and functioning compared to children at baseline, however, they were able to reach comparable ratings at endpoint for most items. Similarly, burden of disease decreased in patients and their carers. OROS MPH was generally safe and well tolerated.

Figure 1

Mean Conners' Parent Rating Scale (CPRS) scores: overall (n = 822) and age subgroups. Data are presented for the intention-to-treat analysis, last observation carried forward. Lower scores denote improvement. Baseline to week 12 improvements were p < 0.0001 for all groups (Wilcoxon test). Assessments at week 6 are only based on data from 224 patients.

Figure 2

Mean Children's Global Assessment Scale (C-GAS) scores. Data are presented for the overall population (n = 822) and by age subgroups (intention-to-treat, last observation carried forward). Higher scores denote improvement. Baseline to week 12 improvements were p < 0.0001 for all groups (Wilcoxon test). Assessments at week 6 are only based on data from 224 patients.

Figure 3

Mean overall improvements in health-related quality of life (ILC-LQ0-28). Data are presented for the overall population and by age subgroups (intention-to-treat, last observation carried forward). High scores denote high quality of life.

Figure 4

Individual health-related quality of life (ILC) item scores assessed by (a) parents (P), and (b) patients (children/adolescents [C]). Mean scores at baseline and at study end (week 12) [intention-to-treat, last observation carried forward]. Dx = diagnostic procedures. Tx = therapeutic procedures. The right sides of the bars represent mean baseline values, the left sides mean values at week 12, the numbers mean improvements between both time points.

Figure 5

Mean scores for problems concerning social interactions and tasks occurring in late afternoon (4 pm to 8 pm). Data presented for the overall population (n = 224) and children and adolescent subgroups (intention-to treat, last observation carried forward). At week 12, all improvements from baseline were significant (p ≤ 0.0001).