Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease.

BACKGROUND: Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis. METHODS: We retrospectively assessed real-world outcomes of RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM, available via Hospital Exemption in Germany. MSC-FFM is provided as frozen cell dispersion for administration as i.v. infusion immediately after thawing, at a recommended dose of 1-2 million MSCs/kg body weight in 4 once-weekly doses. 156 patients, 33 thereof children, received MSC-FFM; 5% had Grade II, 40% had Grade III, and 54% had Grade IV aGvHD. Median (range) number of prior therapies was 4 (1-10) in adults and 7 (2-11) in children. RESULTS: The safety profile of MSC-FFM was consistent with previous reports for MSC therapies in general and MSC-FFM specifically. The overall response rate at Day 28 was 46% (95% confidence interval [CI] 36-55%) in adults and 64% (45-80%) in children; most responses were durable. Probability of overall survival at 6, 12 and 24 months was 47% (38-56%), 35% (27-44%) and 30% (22-39%) for adults, and 59% (40-74%), 42% (24-58%) and 35% (19-53%) for children, respectively (whole cohort: median OS 5.8 months). CONCLUSION: A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD.

Efficacy and tolerability of subcutaneously administered methotrexate including dose escalation in long-term treatment of rheumatoid arthritis in a Japanese population.

OBJECTIVES: The aim of this article is to evaluate the efficacy and safety of subcutaneously administered methotrexate (MTX) for Japanese patients with active rheumatoid arthritis. METHODS: MTX-naïve patients were randomized in a 1:1 ratio to receive a 12-week administration of either 7.5 mg MTX subcutaneously (MJK101, a prefilled syringe for subcutaneous injection) or 8 mg MTX orally in Part 1 of the trial. The primary end point was a 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 12. In the second part, all enrolled patients received MJK101 weekly for 52 weeks with doses starting from 7.5 to 15 mg with 2.5 mg increments with the option of self-administration of MJK101. RESULTS: The efficacy of MJK101 was comparable to oral MTX following 12 weeks of treatment at the starting doses. A numerically higher ACR20 response rate and fewer adverse events in particular gastrointestinal adverse events were observed. During long-term subcutaneous treatment, MJK101 was well tolerated across all tested doses. Patients clinically improved upon dose escalation. CONCLUSIONS: Subcutaneously applied MTX (MJK101) was efficient and well tolerated over a long-term treatment period in the Japanese population with doses up to 15 mg/week. Subcutaneous administration of MTX is a beneficial option for Japanese patients with rheumatoid arthritis.

Sensitivity to change of composite and frequency scores of the neuropsychiatric inventory in mild cognitive impairment.

BACKGROUND: The most appropriate means of capturing data from the Neuropsychiatric Inventory (NPI) must be understood to optimize use of this instrument in clinical trials. The utility of the composite score (frequency times severity) was recently demonstrated in mild and moderate dementia. Determination of frequency compared to composite scores in mild cognitive impairment (MCI) warrants investigation. METHODS: We used the NPI data from a randomized, placebo-controlled, multi-center, 24-week, clinical trial involving 160 patients who were diagnosed with amnestic MCI and had clinically significant neuropsychiatric symptoms (NPS). We calculated standardized changes for both frequency and composite scores. RESULTS: There were improvements in NPI composite scores in both active drug- and placebo-treated patients, with significant superiority of active drug. Standardized changes in severity and composite scores tended to be larger than those in the frequency scores, whereas discrimination between treatment groups was similar for all three scores. CONCLUSIONS: Our findings support the hypothesis that in MCI, as in dementia, the NPI frequency score is not more sensitive to treatment-related change than the composite score. As the severity score adds information, the use of the composite score has better performance characteristics.

Sensitivity to change of composite and frequency scores of the Neuropsychiatric Inventory in mild to moderate dementia.

BACKGROUND: The Neuropsychiatric Inventory (NPI) is widely used to assess psychopathology in dementia. The scoring involves ratings of frequency and severity, as well as the calculation of a composite score. It was suggested recently that, due to lower variance, the frequency score might be more sensitive to detect treatment-related change and to discriminate active treatment from placebo than the composite score, particularly in milder forms of the disease. METHODS: Based on data from three randomized controlled trials in patients with mild to moderate dementia, standardized changes were calculated for both frequency and composite scores for two strata of disease severity. The two strata were formed by dichotomizing the sample along the median score of the short cognitive performance test (SKT) battery. RESULTS: Across all studies and for both severity strata, standardized changes in frequency scores were not consistently larger than those in composite scores and both scores discriminated active treatment from placebo at similar probabilities for type-1 error. CONCLUSION: Our findings do not support the notion that there is a difference between frequency score and composite score with respect to their sensitivity to treatment-related change.

Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial.

OBJECTIVE: To test the efficacy and safety of a once-daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features. METHODS: Multi-centre trial of 410 outpatients with mild to moderate dementia (Alzheimer's disease, vascular dementia or mixed form) scoring between 9 and 23 on the SKT cognitive test battery, at least five on the Neuropsychiatric Inventory (NPI) and three or higher in at least one item of the NPI. Patients were randomly allocated to double-blind treatment with 240 mg of EGb 761 or placebo once daily for 24 weeks. Primary outcomes were the changes from baseline in the SKT total score and the NPI total score. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC), Activities of Daily Living International Scale (ADL-IS), NPI distress score, DEMQOL-Proxy quality-of-life scale and Verbal Fluency Test were secondary outcomes. RESULTS: At endpoint, patients treated with EGb 761 (n = 202) improved by -1.4 (95% confidence interval -1.8; -1.0) points on the SKT and by -3.2 (-4.0; -2.3) on the NPI total score, whereas those receiving placebo (n = 202) deteriorated by +0.3 (-0.1; 0.7) on the SKT and did not change on the NPI total score (-0.9; 0.9). Both drug-placebo comparisons were significant at p < 0.001. EGb 761 was significantly superior to placebo with respect to all secondary outcome measures. Adverse event rates were similar for both treatment groups. CONCLUSIONS: EGb 761, 240 mg once-daily, was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms.

Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.

BACKGROUND: Preventing and managing exacerbations is one major component in COPD treatment. We investigated whether EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides, could prolong time to acute exacerbation in patients with COPD stage II/III. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, patients were randomly allocated to oral 24-week add-on therapy with 3 × 30 drops/day EPs 7630 (n = 99) or placebo (n = 101) to a standardised baseline-treatment. Primary endpoint was time to first exacerbation of COPD. Secondary endpoints were number of exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and tolerability. RESULTS: Median time to exacerbation was significantly prolonged with EPs 7630 compared to placebo (57 versus 43 days, Kaplan-Maier-estimate; p = 0.005, one-sided centre-stratified log-rank test). The superiority of EPs 7630 was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group. CONCLUSIONS: The results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use. Trial Registration No.: ISRCTN01681733.