Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.5058
Peer-review started: March 30, 2022
First decision: June 10, 2022
Revised: July 27, 2022
Accepted: August 17, 2022
Article in press: August 17, 2022
Published online: September 14, 2022
The efficacy and safety of adalimumab have been demonstrated in pivotal trials, but there remained a need to assess more holistically how the clinical results translate into concrete improvements in key aspects of the daily lives of ulcerative colitis (UC) patients, such as symptoms, health-related quality of life (HRQoL), and disability.
Although some patient-reported outcomes (PROs) from existing studies may have items capturing some of these aspects, limited data was available for adalimumab in UC, specifically on psychological distress/depression, disability, fatigue, and pain or sleep quality in real-life setting.
The overarching goal for the UCanADA study was to assess the real-life effectiveness of adalimumab on PRO measures, while taking the opportunity to use the inflammatory bowel disease disability index to assess the impact of adalimumab on key components of patients’ functioning when affected with moderate-to-severe UC.
UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC. Assessments were performed during patients’ routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.
One hundred patients were included in this final analysis, with 94 (94%) patients included in the efficacy population (identified as the intent-to-treat (ITT) population), 48 (48%) patients included in the completers’ population, and 98 (98%) patients included in the safety population. The primary endpoint–the proportion of patients who achieved a change from baseline, defined as an improvement in total severity score relative to baseline, in the Patient Health Questionnaire–9 items (PHQ-9) measure at week 52–was 61.5% [40/65 patients; 95% confidence interval (CI): 49.7%-73.4%] for the ITT population and 65.9% (29/44 patients; 95%CI: 51.9%-79.9%) for completers. The safety profile was consistent with the known safety profile of adalimumab, and no new signal or unexpected trend was identified for the patient population.
At week 52, adalimumab, used in a real-life study, was effective in reducing depressive symptoms in patients with UC, with more than 60% of the patients achieving an improvement the PHQ-9 with a mean improvement of 2.4 points. Thus, the treatment with adalimumab contributed to reducing the depressive symptoms frequently experienced in patients with UC as well as improving a broad range of PROs such as HRQoL and work productivity, as assessed with PRO instruments. The safety profile was consistent with the known safety profile of adalimumab, and no new signal or unexpected trend was identified for the patient population.
Improvements in PHQ-9 were associated with clinical remission. Beyond the PHQ-9, significant improvements in several PROs were observed suggesting an improvement in HRQoL and work productivity as well. The population in the study, as well as the inclusion and exclusion criteria, was representative of the target population. In addition, coinciding the study visits with the patient’s routine care visit schedule helped increase generalizability of the PRO instruments by decreasing the impact on real life.