Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies.

The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35).

Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial.

We report results of a phase 2, randomized, multicenter, open-label, two-arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in sensitized recipients of living-donor kidney transplants requiring pretransplant desensitization (NCT01399593). In total, 102 patients underwent desensitization. Posttransplant, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplant treatment failure rate, a composite of: biopsy-proven acute AMR (Banff 2007 grade II or III; assessed by blinded central pathology); graft loss; death; or loss to follow-up. Eculizumab was well tolerated with no new safety concerns. No significant difference in treatment failure rate was observed between eculizumab (9.8%) and SOC (13.7%; P = .760). To determine whether data assessment assumptions affected study outcome, biopsies were reanalyzed by central pathologists using clinical information. The resulting treatment failure rates were 11.8% and 21.6% for the eculizumab and SOC groups, respectively (nominal P = .288). When reassessment included grade I AMR, the treatment failure rates were 11.8% (eculizumab) and 29.4% (SOC; nominal P = .048). This finding suggests a potential benefit for eculizumab compared with SOC in preventing acute AMR in recipients sensitized to their living-donor kidney transplants (EudraCT 2010-019630-28).

A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

BACKGROUND: Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy. METHODS: Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status. RESULTS: At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes. CONCLUSIONS: Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients.

The impact of buprenorphine transdermal delivery system on activities of daily living among patients with chronic low back pain: an application of the international classification of functioning, disability and health.

OBJECTIVES: The buprenorphine transdermal delivery system (BTDS) is indicated for reduction of pain in moderate to severe chronic low back pain (CLBP), which can affect patients' ability to perform routine activities of daily living (ADLs). This post hoc analysis of clinical trial data examines the impact of BTDS treatment on CLBP patients' ability to perform ADLs that relate to functioning with low back pain. METHODS: Data are drawn from a multicenter, enriched enrollment, randomized, placebo-controlled, double-blind 12-week trial of BTDS for pain control among opioid-naive patients with moderate to severe CLBP. The 23 selected ADLs are those that (1) appear in the Low Back Pain Core Set of the International Classification of Functioning, Disability and Health and (2) link to the content of 3 patient-reported outcome instruments administered during the trial. Logistic regression models estimated the odds ratios (ORs) of BTDS patients' ability to perform each ADL at 12 weeks, controlling for baseline ability, relative to placebo. RESULTS: The ORs for 10 ADLs related to sleeping, lifting, bending, and working reached multiplicity-adjusted statistical significance and indicated a greater ability to perform ADLs among BTDS users than among the placebo group. These 10 ORs ranged from 1.9 (no physical health-related restrictions on the kind of work performed) to 2.4 (being able to sleep undisturbed by pain). DISCUSSION: These results suggest that for patients with moderate to severe CLBP, 12 weeks use of BTDS improves the ability to carry out certain ADLs related to sleeping, lifting, bending, and working.

Buprenorphine transdermal system and quality of life in opioid-experienced patients with chronic low back pain.

OBJECTIVES: To evaluate the impact of 12 weeks of treatment with Butrans® (buprenorphine) transdermal system (BTDS) on the health-related quality of life (HRQoL) for patients with chronic low back pain (CLBP), and the maintenance of effects over 52 weeks. RESEARCH DESIGN AND METHODS: A multicenter, enriched, double-blind (DB), randomized trial comparing BTDS 20 µg/h (BTDS 20) against 5 µg/h (BTDS 5) for treatment of opioid-experienced patients with moderate-to-severe CLBP, including a 52-week open-label (OL) extension phase. MAIN OUTCOME MEASURES: QoL was measured with the SF-36v2 survey before and after an OL run-in period with BTDS 20, three times during the DB phase, and seven times over the extension phase. This post hoc analysis tested for SF-36v2 score differences between treatment groups during the DB phase and maintenance of effects over the extension phase. RESULTS: At 12 weeks, BTDS 20 produced larger improvements than BTDS 5 in role limitations due to physical health, bodily pain and overall physical QoL (p < 0.01). Treatment group differences in overall physical QoL were sustained throughout the DB phase. Quality-of-life improvements associated with BTDS 20 persisted through the extension phase. CONCLUSIONS: These data suggest that opioid-experienced moderate-to-severe CLBP patients receiving BTDS 20 exhibited better QoL than patients receiving BTDS 5.

A randomized, placebo-controlled study of the impact of the 7-day buprenorphine transdermal system on health-related quality of life in opioid-naïve patients with moderate-to-severe chronic low back pain.

UNLABELLED: This study evaluated the impact of treatment with Buprenorphine Transdermal System (BTDS) on the health-related quality of life for patients with moderate-to-severe chronic low back pain (CLBP), and the correspondence between quality of life and pain. A multicenter, enriched, double-blind (DB), placebo-controlled, randomized trial evaluated BTDS 10 and 20 µg/hour for treatment of opioid-naïve patients with moderate-to-severe CLBP. The SF-36v2 survey, which measures 8 domains of quality of life, was administered at screening and following an open-label run-in period with BTDS and at weeks 4, 8, and 12 of the DB phase. Post hoc analyses compared SF-36v2 scores between BTDS and placebo groups during the DB phase. Condition burden was examined through comparisons with a U.S. general population sample. Correlations examined the correspondence between quality of life and pain measures. BTDS produced larger improvements than placebo at 12 weeks in all quality-of-life domains (Ps < .05). Treatment group differences in both physical and mental quality of life emerged by 4 weeks. Patients' pretreatment quality of life was worse than that in the general population (Ps < .05); only BTDS treatment eliminated deficits in pain, social functioning, and role limitations due to emotional health. Improvements in quality of life were moderately associated with pain reduction. These data suggest that moderate-to-severe CLBP patients receiving BTDS exhibited better quality of life than patients receiving placebo. PERSPECTIVE: This post hoc analysis suggests that patients with moderate-to-severe CLBP treated with BTDS exhibit better health-related quality of life than those using placebo within 4 weeks of treatment, and were more likely to exhibit clinically meaningful improvements in quality of life following 12 weeks of treatment.

The economic benefits of supported employment for persons with mental illness.

BACKGROUND: Policies and programs that emphasize employment for persons with mental illness are often promoted with the goals of improving economic self-sufficiency and reducing dependence on public welfare programs. At present, there is little empirical evidence about the actual effect of vocational interventions on economic self-sufficiency or on use of public benefits by persons with mental illness. STUDY AIMS: This study provides a preliminary look at how participating in supported employment, a form of vocational rehabilitation emphasizing ongoing support in competitive jobs, affects the amount that participants earn from work and the total amount of income they receive from all sources. Further, we examine the extent to which receiving public benefits affects the amount earned from private employment, taking into consideration other factors that might be associated with benefit status. METHODS: Data are from a randomized trial of supported employment interventions. This analysis followed 137 of those study participants with severe mental illness for 18 months after they enrolled in either of two supported employment programs. Income from various sources was estimated based on interviews with study participants upon study entry and at six-month intervals thereafter. Changes in income from work, government and other sources were analyzed using paired Wilcoxon matched-pairs signed-ranks tests and t-tests. Using ordinary least-squares regression, we analyzed the effect of benefit status on changes in earnings, taking into account diagnosis, work history, education, program type, site of program, psychiatric symptoms, global functioning and previous earnings. RESULTS: Estimated total income increased by an average of $134 (US) per month after enrolling in supported employment. More than three-quarters of this increase was from government sources, such as Social Security and educational grants. The increase in government income was largely due to participants applying for and getting cash benefits for the first time. Social Security payments for those receiving benefits before enrollment did not change significantly. A small group of persons (n = 22) who did not receive Social Security benefits before or after enrolment earned significantly more from competitive employment after enrolling than did those who received benefits. This finding persisted after taking into acount differences in work history, clinical and functional variables and education. LIMITATIONS: Because of the relatively small sample size and the lack of continuous measures of income these results should be considered preliminary. CONCLUSIONS: Supported employment, one of the more effective forms of vocational rehabilitation for persons with mental illness, did not reduce dependence on government support. Receiving government benefits was associated with lower earnings from work. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: These findings suggest that most persons in treatment for severe mental illness need continued public financial support even after enrolling in vocational rehabilitation programs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Undoubtedly increased labor force participation can benefit persons with mental illness in a number of ways. However, policy makers should be careful about justifying increased access to vocational programs on the basis of reduced spending for income support. Further, targeting such programs only to persons receiving income support may overlook the clients who can benefit most: those who are not currently receiving benefits. IMPLICATIONS FOR FURTHER RESEARCH: Policy makers need a better understanding of how vocational interventions and income support programs affect the income and well-being of persons with mental illness. Studies similar to this one should be repeated with larger, more diverse samples that will allow use of instrumental variables statistical techniques.