Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis.

BACKGROUND & AIMS: New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. METHODS: We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. RESULTS: Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. CONCLUSIONS: Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417.

Audio-recorded guided imagery treatment reduces functional abdominal pain in children: a pilot study.

OBJECTIVE: This study was designed to develop and to test a home-based, guided imagery treatment protocol, using audio and video recordings, that is easy for health care professionals and patients to use, is inexpensive, and is applicable to a wide range of health care settings. METHODS: Thirty-four children, 6 to 15 years of age, with a physician diagnosis of functional abdominal pain were assigned randomly to receive 2 months of standard medical care with or without home-based, guided imagery treatment. Children who received only standard medical care initially received guided imagery treatment after 2 months. Children were monitored for 6 months after completion of guided imagery treatment. RESULTS: All treatment materials were reported to be self-explanatory, enjoyable, and easy to understand and to use. The compliance rate was 98.5%. In an intention-to-treat analysis, 63.1% of children in the guided imagery treatment group were treatment responders, compared with 26.7% in the standard medical care-only group (P = .03; number needed to treat: 3). Per-protocol analysis showed similar results (73.3% vs 28.6% responders). When the children in the standard medical care group also received guided imagery treatment, 61.5% became treatment responders. Treatment effects were maintained for 6 months (62.5% responders). CONCLUSION: Guided imagery treatment plus medical care was superior to standard medical care only for the treatment of abdominal pain, and treatment effects were sustained over a long period.