Real-World, Non-Interventional, Observational Study of Hydroxyzine Hydrochloride in Chronic Pruritus: a Prospective, Non-Comparative Study

Adult patients of either sex, ≥ 18 years of age, suffering from chronic pruritus due to dermatological conditions and for whom the physician had taken a decision to prescribe hydroxyzine hydrochloride were included in study. Those with pruritus due to systemic causes, known hypersensitivity to the study drug, pregnant or lactating women, those receiving any centrally acting medications or those with known neurological conditions were excluded from the study.

The study documents were reviewed and approved by the respective Institutional/Independent Ethics Committees (please see supplementary material for list of Ethics Committees), and the study was conducted in accordance with the principles of the Declaration of Helsinki (World Medical Association) and Good Clinical Practice guidelines issued by the ICMR & DCGI, Government of India. All the patients received explanations about the study details and were provided the opportunity to raise any queries/doubts about the study. Written informed consent was obtained from all patients before enrolment. The study was registered in the clinical trials registry of India (CTRI/2017/06/008847; registered on: 15/06/2017).

Because of the observational nature of this study, patients who were prescribed oral hydroxyzine hydrochloride (Atarax^® 10/25 mg tablets, Dr. Reddy’s Laboratories Ltd., India) for a 12-week period at the discretion of the clinician were enrolled. The dosing allowed followed the prescribing information, i.e. up to 25 mg four times daily. Patients were allowed to continue other concomitant medications.

Detailed medical history was taken and clinical examination was performed at baseline. The patients were followed up as per routine clinical practice. However, clinical assessments were recorded at baseline and after 2, 4, 8 and 12 weeks of starting hydroxyzine hydrochloride treatment. The effect of pruritus on the quality of life was assessed using the Dermatology Life Quality Index (DLQI) questionnaire, which is a ten-item validated questionnaire for assessment of quality of life (QOL) in patients with dermatological disorders [13‐15]. The effect of pruritus on the patient’s life was interpreted based on the total DLQI scores of ten items: no effect at all on the patient’s life (score 0–1), a small effect on the patient’s life (scores 2–5), a moderate effect on the patient’s life (scores 6–10) and a very large effect on the patient’s life (scores 11–20). Pruritus severity was assessed using the 5-D itch scale, which measures pruritus according to five dimensions, i.e. degree, duration, direction, disability and distribution [16, 17]. Single-item domain scores (duration, degree and direction) were marked on a range of 1–5, whereas the disability domain had four items that assess the impact of itching on daily activities: sleep, leisure/social activities, housework/errands and work/school, and for the distribution domain, the number of affected body parts was tallied (potential sum 0–16). The sum for the distribution domain was sorted into five scoring bins: sum of 0–2 = score 1, sum of 3–5 = score 2, sum of 6–10 = score 3, sum of 11–13 = score 4 and sum of 14–16 = score 5. The score for the disability domain was achieved by taking the highest score on any of the four items. The scores of each of the five domains were arrived at separately and then summed together to obtain a total 5-D itch score, and the total score ranged from 5 (no pruritus) to 25 (most severe pruritus).

The primary study outcome was improvement in DLQI scores from baseline at the end of the 12-week study period. Secondary outcomes were improvement in 5-D itch score at the end of 12 weeks and safety. Safety was assessed based on spontaneous reports generated by the clinician.

The estimated sample size for 80% power for this observational study was 400 based on the assumption of 5% error and expecting a response rate of 50% for improvement in the DLQI score. The efficacy analysis was done on the full analysis set (FAS), i.e. those patients who completed the 12-week study period as well as those who left the study early because of being either cured (treatment discontinuation) or lost to follow-up and had at least one follow-up visit completed. Data from all patients enrolled in the study was included for safety analysis, i.e. the intent-to-treat set (ITTS), which included all 400 patients enrolled in the study. Continuous data are summarized as means, standard deviation (SD), median and range. The baseline scores were compared with scores at follow-up visits (pairwise) using the Wilcoxon test, and scores at all visits were analysed using the Friedman test (non-parametric repeat measures ANOVA). The changes from baseline [mean, SD, 95% confidence interval (CI) and percentage change] in the DLQI scores and 5-D itch scores were computed for each follow-up visit (2, 4, 8 and 12 weeks) and were presented as numbers and percentages for the FAS. Since many patients were terminated early at investigator’s discretion because they had complete symptomatic relief and there was no further need for antihistamine therapy, cure rates for symptoms were computed at each follow-up visit and are presented as numbers with percentages.

Four hundred patients with chronic pruritus due to dermatological causes were enrolled from seven study sites; of these, nine patients did not have a single follow-up visit and were excluded from the full analysis set (FAS, n = 391). Amongst the 391 patients completing at least 1 follow-up visit, 25 patients completed 2 weeks, 176 completed 4 weeks, 14 completed 8 weeks and 176 completed 12 weeks of the study period. The demographic profile and vital parameters at baseline for all patients (ITTS) and those in the FAS are presented in Table 2. The primary diagnosis of chronic pruritus recorded included conditions such as allergy, psoriasis, dermatophytosis, acne, urticaria, xerosis and other dermatological conditions. Being an observational study, the dose and dosing schedule were decided by the treating physician based on patient characteristics. The dosing allowed was as per the prescribing information, i.e. up to 25 mg four times daily. While 272 patients received 10 mg, 122 patients received 25 mg. The majority (n = 313) of the patients were administered the drug once daily, while others received it up to four times daily (Table 3). Two hundred fourteen patients were on hydroxyzine therapy alone without any concomitant medications (54.31%).

Tables 4 and 5 show the descriptive data for DLQI and 5-D itch scores at all visits, respectively. The post-treatment scores for the DLQI and 5-D itch scale were significantly lower than the baseline scores, and there was a significant reduction in the scores at all follow-up visits (p < 0.0001). The percentage reductions from baseline in DLQI scores and 5-D itch scores are presented in Figs. 1 and 2, respectively.

Of 400 patients, only 11 (2.8%) patients reported adverse events. Dizziness was the most common adverse event reported by four patients (1.0%), while constipation was reported by two patients (0.5%), drowsiness by two patients (0.5%), dry mouth by two patients (0.5%) and sedation by one patient (0.3%). All events were of mild-to-moderate severity not requiring any interventions and resolved without sequelae. There was no predilection for any adverse event for any particular age group or sex of the patients. No serious adverse events were reported in this study.