Validation of a questionnaire to assess niacin-induced cutaneous flushing

Background: Niacin is currently the most effective approved agent for raising high-density lipoprotein cholesterol. However, niacin-induced cutaneous flushing (redness, warmth, tingling and/or itching) significantly limits patient acceptance. To further characterize flushing, a patient-reported Flushing Symptom Questionnaire* (FSQ) was developed and validated. Methods: The FSQ was validated in an 8-week, randomized, double-blind, placebo-controlled trial of extended-release (ER) niacin and placebo. The primary flushing endpoint of the study was based on the single Global Flushing Severity Score (GFSS), an item within the FSQ, which assesses overall flushing severity on a 0-10 discretized analog scale. Results: A total of 175 patients were randomized to one of four treatment groups (sequences of placebo and ER niacin [given as niacin (NIASPAN) 1 g (N1) and 2g (N2)]. Test-retest reliability and reproducibility coefficients for the single-item GFSS were all above 0.75. Construct validity was supported by moderate to strong correlations (r> 0.5) with other FSQ items. All FSQ item scores and specifically the GFSS discriminated between treatment groups and demonstrated expected relationships with predefined known groups. The GFSS demonstrated high responsiveness in patients who switched from ER niacin to placebo. The ability of the GFSS and GFBS to discriminate changes in flushing symptoms in patients who increased drug dose was less than expected possibly due to accommodation to the flushing effects of niacin over time; differential drop-out due to flushing; and/or FSQ items not being sensitive enough to detect a change that was present. Conclusions: The FSQ items and specifically the Global Flushing Severity Score (GFSS), are reliable and valid measures to assess niacin-induced flushing.