Pregabalin in fibromyalgia - responder analysis from individual patient data

<p>Abstract</p> <p>Background</p> <p>Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.</p> <p>Methods</p> <p>We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.</p> <p>Results</p> <p>Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.</p> <p>Conclusions</p> <p>Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.</p

Sex-related differences of cortical thickness in patients with chronic abdominal pain.

Regional reductions in gray matter (GM) have been reported in several chronic somatic and visceral pain conditions, including irritable bowel syndrome (IBS) and chronic pancreatitis. Reported GM reductions include insular and anterior cingulate cortices, even though subregions are generally not specified. The majority of published studies suffer from limited sample size, heterogeneity of populations, and lack of analyses for sex differences. We aimed to characterize regional changes in cortical thickness (CT) in a large number of well phenotyped IBS patients, taking into account the role of sex related differences.Cortical GM thickness was determined in 266 subjects (90 IBS [70 predominantly premenopausal female] and 176 healthy controls (HC) [155 predominantly premenopausal female]) using the Laboratory of Neuro Imaging (LONI) Pipeline. A combined region of interest (ROI) and whole brain approach was used to detect any sub-regional and vertex-level differences after removing effects of age and total GM volume. Correlation analyses were performed on behavioral data.While IBS as a group did not show significant differences in CT compared to HCs, sex related differences were observed both within the IBS and the HC groups. When female IBS patients were compared to female HCs, whole brain analysis showed significant CT increase in somatosensory and primary motor cortex, as well as CT decrease in bilateral subgenual anterior cingulate cortex (sgACC). The ROI analysis showed significant regional CT decrease in bilateral subregions of insular cortex, while CT decrease in cingulate was limited to left sgACC, accounting for the effect of age and GM volume. Several measures of IBS symptom severity showed significant correlation with CT changes in female IBS patients.Significant, sex related differences in CT are present in both HCs and in IBS patients. The biphasic neuroplastic changes in female IBS patients are related to symptom severity