Optimizing Selection of Biologics in Inflammatory Bowel Disease: Development of an Online Patient Decision Aid Using Conjoint Analysis.

OBJECTIVES: Recent drug approvals have increased the availability of biologic therapies for inflammatory bowel disease (IBD), making it difficult for patients with ulcerative colitis (UC) and Crohn's disease (CD) to navigate treatment options. Here we developed a conjoint analysis to examine patient decision-making surrounding biologic medicines for IBD. We used the results to create an online patient decision aid that generates a unique "preferences report" for each patient to assist with shared decision-making with their provider. METHODS: We administered an adaptive choice-based conjoint survey to IBD patients that quantifies the relative importance of biologic attributes (e.g., efficacy, side effect profile, mode of administration, and mechanism of action) in decision making. The conjoint software determined individual patient preferences by calculating part-worth utilities for each attribute. We conducted regression analyses to determine if demographic and disease characteristics (e.g., type of IBD and severity) predicted how patients made decisions. RESULTS: 640 patients completed the survey (UC=304; CD=336). In regression analyses, demographics and IBD characteristics did not predict individual patient preferences; the main exception was IBD type. When compared to UC, CD patients were more likely to report side effect profile as most important (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.16-2.30). Conversely, those with UC were more likely to value therapeutic efficacy (OR 1.41, 95% CI 1.01-2.00). CONCLUSIONS: Biologic decision-making is highly personalized; demographic and disease characteristics poorly predict individual preferences, indicating that IBD patients are unique and difficult to statistically categorize. The online decision tool resulting from this study (www.ibdandme.org) may be used by patients to support shared decision-making and optimize personalized biologic selection with their provider.

A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast.

PURPOSE: Local transdermal therapy to the breast may achieve effective target-organ drug delivery, while diminishing systemic effects. We conducted a randomized, double-blind, placebo-controlled phase II trial comparing transdermal 4-hydroxytamoxifen gel (4-OHT) to oral tamoxifen (oral-T) in women with ductal carcinoma in situ (DCIS). METHODS: Twenty-seven pre- and postmenopausal women were randomized to 4-OHT (4 mg/day) or oral-T (20 mg/day) for 6 to 10 weeks before surgery. Plasma, nipple aspirate fluid, and breast adipose tissue concentrations of tamoxifen and its major metabolites were determined by liquid chromatography/tandem mass spectrometry. The primary endpoint was Ki67 labeling in DCIS lesions, measured by immunohistochemistry. In plasma, insulin-like growth factor-1 (IGFI), sex hormone-binding globulin (SHBG), and coagulation protein concentrations were determined. RESULTS: Posttherapy Ki67 decreased by 3.4% in the 4-OHT and 5.1% in the oral-T group (P ≤ 0.03 in both, between-group P = 0. 99). Mean plasma 4-OHT was 0.2 and 1.1 ng/mL in 4-OHT and oral groups, respectively (P = 0.0003), whereas mean breast adipose tissue concentrations of 4-OHT were 5.8 ng/g in the 4-OHT group and 5.4 ng/g in the oral group (P = 0.88). There were significant increases in plasma SHBG, factor VIII, and von Willebrand factor and a significant decrease in plasma IGFI with oral-T, but not with 4-OHT. The incidence of hot flashes was similar in both groups. CONCLUSIONS: The antiproliferative effect of 4-OHT gel applied to breast skin was similar to that of oral-T, but effects on endocrine and coagulation parameters were reduced. These findings support the further evaluation of local transdermal therapy for DCIS and breast cancer prevention.

A phase I trial of aminolevulinic acid-photodynamic therapy for treatment of oral leukoplakia.

BACKGROUND: Photodynamic therapy with aminolevulinic acid (ALA PDT) for oral leukoplakia has shown promising effects in regression of oral leukoplakia. Although ALA has been extensively studied and is an ideal photosensitizer, the optimal light dose for treatment of oral leukoplakia has not been determined. We conducted a phase I study to determine MTD and DLT of PDT in patients treated with ALA for leukoplakia. METHODS: Patients with histologically confirmed oral leukoplakia received a single treatment of ALA PDT in cohorts with escalating doses of light (585nm). Clinical, histologic, and biologic markers were assessed. RESULTS: Analysis of 11 participants is reported. No significant toxicity from ALA PDT was observed in patients who received ALA with a light dose of up to 4J/cm(2). One participant experienced transient grade 3 transaminase elevation due to ALA. One participant had a partial clinical response 3months after treatment. Biologic mucosal risk markers showed no significant associations. Determination of MTD could not be accomplished within a feasible timeframe for completion of the study. CONCLUSIONS: ALA PDT could be safely administered with a light dose up to 4J/cm(2) and demonstrated activity. Larger studies are needed to fully elucidate the MTD and efficacy of ALA-PDT.