Clinical effect of mirikizumab treatment on bowel urgency in patients with moderately to severely active ulcerative colitis and the clinical relevance of bowel urgency improvement for disease remission

Background: Bowel urgency reduces ulcerative colitis patients' quality of life. Mirikizumab, a p19-directed anti-IL-23 antibody, demonstrates ulcerative colitis efficacy. Mirikizumab efficacy to reduce bowel urgency and bowel urgency association with other endpoints were analyzed in 2 Phase 3 trials. Methods: LUCENT-1 (Induction): 1162 patients randomized 3:1 to intravenous 300 mg mirikizumab or placebo every 4 weeks for 12 weeks. LUCENT-2 (Maintenance): 544 mirikizumab responders during induction were re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks (52 weeks of continuous treatment). Bowel urgency was measured using the Urgency Numeric Rating Scale (0–10); for patients with LUCENT-1 baseline score ≥3, bowel urgency clinically meaningful improvement (≥3-point decrease) and remission (score ≤1) rates in mirikizumab versus placebo groups were compared at Weeks 12 and 52. Associations between bowel urgency and other efficacy endpoints were assessed at Weeks 12 and 52. Results: A significantly higher proportion of mirikizumab patients versus placebo achieved clinically meaningful improvement in bowel urgency and remission at Weeks 12 and 52. Significantly higher percentages of patients achieving bowel urgency clinically meaningful improvement or remission, compared with those who did not, also achieved endpoints for clinical, corticosteroid-free, endoscopic, and symptomatic remission; clinical response; normalized fecal calprotectin and C-reactive protein; and improved quality of life. Conclusions: In patients with ulcerative colitis, bowel urgency improvement was associated with better clinical outcomes than in patients without improvement during induction and maintenance. A greater proportion of mirikizumab patients achieved sustainable bowel urgency improvement and remission compared to placebo patients

Motor imagery and action observation: cognitive tools for rehabilitation

Rehabilitation, for a large part may be seen as a learning process where old skills have to be re-acquired and new ones have to be learned on the basis of practice. Active exercising creates a flow of sensory (afferent) information. It is known that motor recovery and motor learning have many aspects in common. Both are largely based on response-produced sensory information. In the present article it is asked whether active physical exercise is always necessary for creating this sensory flow. Numerous studies have indicated that motor imagery may result in the same plastic changes in the motor system as actual physical practice. Motor imagery is the mental execution of a movement without any overt movement or without any peripheral (muscle) activation. It has been shown that motor imagery leads to the activation of the same brain areas as actual movement. The present article discusses the role that motor imagery may play in neurological rehabilitation. Furthermore, it will be discussed to what extent the observation of a movement performed by another subject may play a similar role in learning. It is concluded that, although the clinical evidence is still meager, the use of motor imagery in neurological rehabilitation may be defended on theoretical grounds and on the basis of the results of experimental studies with healthy subjects