|Year : 2022 | Volume
| Issue : 2 | Page : 59-65
Bilastine in pruritus associated with dermatological conditions
Abhay Talathi1, Prajakta Talathi1, Jalpa Kapadia Rachh2, Kaleem Khan3, Dhiraj Dhoot4, Gaurav Anil Deshmukh4
1 Consultant Dermatologist, Skinspace Clinic, Mumbai, Maharashtra, India
2 Consultant Dermatologist, Devasya Skin Care Clinic, Mumbai, Maharashtra, India
3 Consultant Dermatologist, Skin indulgence Clinic, Mumbai, Maharashtra, India
4 Global Medical Affairs, Glenmark Pharmaceuticals Ltd, Mumbai, Maharashtra, India
|Date of Submission||26-Apr-2021|
|Date of Acceptance||22-Dec-2022|
|Date of Web Publication||5-Jan-2023|
Consultant Dermatologist, Skinspace Clinic, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Pruritus is a common and unpleasant symptom associated with multiple skin diseases. As histamine plays a central role in pruritus pathology, H1 antihistamines are frequently used in its management. Bilastine is a potent second-generation antihistamine approved for the management of urticaria. However, there are few studies showing its effectiveness and safety in pruritus associated with skin diseases. Materials and Methods: In this multicenter, open-label study, patients with pruritus associated with various skin diseases received bilastine 20 mg once daily for 4 weeks. Patients were evaluated for improvement in their pruritus based on the 5D itch score and Dermatology Life Quality Index (DLQI). Safety of bilastine was assessed by monitoring the incidence of adverse events during the study period. Results: A total of 116 patients with urticaria (n = 22), eczema/dermatitis (n = 27), lichen planus (n = 9), pPsoriasis (n = 11), dermatophytosis (n = 42), and others (n = 5) were included in the study. There was a significant improvement in the 5D itch score at the end of therapy (16.18 ± 2.81 vs. 6.20 ± 1.38 P < 0.0001) in all patients. Bilastine improved the DLQI at week 4 in all disease groups (11.83 ± 4.97 vs. 2.15 ± 2.68; P < 0.0001). The treatment was well tolerated. Conclusion: Bilastine is associated with significant improvement in pruritus associated with multiple dermatological disorders with a very good safety profile.
Keywords: 5D itch score, bilastine, DLQI, pruritus
|How to cite this article:|
Talathi A, Talathi P, Kapadia Rachh J, Khan K, Dhoot D, Deshmukh GA. Bilastine in pruritus associated with dermatological conditions. Indian J Drugs Dermatol 2022;8:59-65
|How to cite this URL:|
Talathi A, Talathi P, Kapadia Rachh J, Khan K, Dhoot D, Deshmukh GA. Bilastine in pruritus associated with dermatological conditions. Indian J Drugs Dermatol [serial online] 2022 [cited 2023 Mar 24];8:59-65. Available from: https://www.ijdd.in/text.asp?2022/8/2/59/367117
| Introduction|| |
Pruritus is a common and unpleasant sensation in the skin causing an intense desire to scratch and thus negatively affects the psychological and physical aspects of life., It is a common symptom associated with skin diseases like contact dermatitis, urticaria, prurigo, eczema, and can also emerge from systemic diseases like metabolic disorders, psychiatric disorders, endocrine disorders, and cancer. It is also one of the most common symptoms to visit a dermatologist.
Although multiple mediators are involved in pruritus, histamine is considered to have a predominant role in pruritus. Histamine via histamine 1 receptor (H1R) activates phospholipase C and phospholipase A, which in turn stimulates transient receptor potential cation channel on mechanically insensitive C-type fibers producing itch sensation. Hence, H1 antihistamines are most commonly prescribed in the management of pruritus.
Bilastine is a potent, non-sedating second-generation H1-antihistamine with demonstrable efficacy for the symptomatic treatment of chronic spontaneous urticaria (CSU). It is effective in reducing symptoms of pruritus and wheals at a dose of 20 mg once a day for 28 days, thus improving quality of life (QoL). It also significantly reduces histamine-induced wheal and flare responses in healthy volunteers,,, with a more rapid onset of action than cetirizine 10 mg, desloratadine 5 mg and rupatadine 10 mg, and superiority over these drugs for inhibiting itching sensation.
Although bilastine has been approved for the treatment of urticaria, there are studies that have shown the use of bilastine in the treatment of pruritus. As per a study by Serra et al. conducted in patients with CSU and other skin diseases, improvement was seen with bilastine in pruritus severity score and Dermatology Life Quality Index (DLQI) at week 8 as compared to baseline. A phase III study by Yagami et al. also showed the long-term efficacy and safety of bilastine 20 mg in Japanese patients with CSU or pruritus associated with skin diseases. However, there are no studies of bilastine in the management of pruritus associated with skin diseases in India. Thus, we planned to conduct this study to evaluate the effectiveness and safety of bilastine in the management of pruritus associated with skin disorders.
| Materials and Methods|| |
This study was designed as a 4-week, interventional, multicenter study to evaluate the effectiveness and safety of bilastine in the management of patients with pruritus associated with skin disorders. Patients of either gender between the age group of 18 and 60 years and with a history of pruritus associated with skin disorders were included in the study. Patients with physical urticaria, pruritus due to metabolic diseases, neurologic disorders, endocrine diseases, psychiatric disorders, and cancer and patients with a known history of clinically significant disease, for example, cardiac, respiratory, gastrointestinal, and renal disease were excluded from the study.
At the screening visit, patients were assessed for the inclusion and exclusion criteria and underwent for detail medical history and clinical examination. All the eligible patients were put on washout period of 1 week in which they were not allowed to use any medication related to pruritus; however, corticosteroid (30 mg prednisone) was allowed to use as a rescue medication for intolerant pruritus.
At Visit 2 (Day 1), patients were assessed for pruritus by the responsible physician using a multidimensional 5D itch scale which has a questionnaire on duration, degree, direction, disability, and distribution of pruritus. The effect of pruritus on QoL was also assessed by DLQI questionnaire. The same procedure was repeated in weeks 2 and 4. All enrolled patients were assessed for safety also.
All the patients were treated with oral bilastine 20 mg once daily for 4 weeks for pruritus in addition to their primary treatment.
Effectiveness assessments were done by evaluating the pruritus of the patients using a 5D itch scale and QoL assessment was done using DLQI. Safety was assessed by monitoring the incidences of treatment-emergent adverse events (TEAEs), treatment-related AEs, and AEs/SAEs leading to study withdrawal.
Efficacy endpoints: Primary efficacy endpoint was the percentage of patients showing complete improvement in pruritus on the 5D itch scale at the end of the therapy (5D itch score of 5). The secondary endpoints were the proportion of patients showing near-complete improvement in pruritus on 5D itch scale at the end of therapy (5D itch score of 6–8), change in total 5D itch score at the end of therapy, change in total 5D itch score in individual disease change in each domain of 5D itch score at the end of therapy and improvement in QoL of patient based on DLQI from baseline.
Safety endpoint: Safety of treatment was assessed by analyzing the percentage of patients showing adverse events to bilastine during the study period.
Results were presented as mean scores, and groups are compared using one-way ANOVA with the Tukey HSD test. Correlations were calculated using the Pearson correlation test. Data were analyzed using the SPSS software program, version 2.0.
This study was approved by the ethics committee (Suraksha Ethics committee; Reg. no. ECR/644/Inst/MH/2014/RR-17) and was registered with clinical trials (CTRI/2020/06/025826).
| Results|| |
A total of 119 patients were enrolled in the study; three patients were lost to follow-up and 116 patients were included in the final study analysis. The baseline demographic details of the patients are shown in [Table 1].
Primary Efficacy End Point
The 5D itch scale was able to detect significant changes in pruritus over the follow-up period. Of the 116 patients assessed at baseline and week 4, 55 patients (47.41%) showed complete improvement in their pruritus (5D itch score = 5). [Figure 1]
|Figure 1: Proportion of patients showing improvement in their pruritus based on 5D itch scale at the end of treatment period|
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Secondary Efficacy End Points
Improvement in pruritus
A total of 57 patients (49.14%) showed almost complete improvement (5D itch score 6–8) in their pruritus at the end of therapy. Four patients (3.45%) failed to show any improvement in their pruritus at the end of the bilastine 20 mg treatment [Figure 1].
Total 5D itch score
There was a significant reduction in total 5D itch score over the treatment period (16.18 ± 2.81 vs. 6.20 ± 1.38; P < 0.0001) [Table 2]. There was a statistical improvement in each domain of the mean 5D itch score [Figure 2] and [Table 2]. On subclassification of pruritus etiology groups, eczema group had the highest percentage of patients (59.26%, n = 16/27) with complete control of pruritus (5D Itch score = 5) followed by dermatophytosis (47.6%, n = 20/42), psoriasis (45.5%, n = 5/11), CSU (34.8%, n = 8/22), and lichen planus (33.33%, n = 3/9) [Figure 3].
|Figure 2: Improvement in Pruritus based on 5D itch score in individual disease|
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|Figure 3: Number of patients in etiology group achieving complete control of pruritus|
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Individual domain of 5D itch scale
Similarly significant improvement in each of the five individual domains of 5D itch scale was observed during the study duration. [Table 2], [Figure 4].
|Figure 4: Improvement in individual domain of 5D itch score during study period|
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At baseline, the duration of patient’s pruritus was approximately 12–18 h/day, which was significantly reduced with an average pruritus duration less than 6 h/day at the end of the therapy.
At baseline, the degree of pruritus patients pruritus was moderate to severe (3.65 ± 0.62), which was significantly decreased at the end of therapy (1.45 ± 0.51; P < 0.0001).
At baseline, patients complained regarding worsening of their pruritus (4.44 ± 0.52), which was significantly improved at the end of the treatment period (1.43 ± 0.49; P < 0.0001).
Patients’ QoL was significantly disturbed at baseline with respect to daily activities like sleep, leisure, office work or school work (3.13 ± 1.08). Bilastine 20mg treatment was associated with significant improvement in patients’ daily activities thus improving the patients’ QoL (1.22 ± 0.49; P < 0.0001)
The mean distribution of pruritus at baseline was 2.10 ± 0.78 suggesting involvement of 3–5 areas of body. After 4 weeks of treatment, there was a significant reduction in distribution of pruritus (1.04 ± 0.20; P < 0.0001).
Dermatology Life Quality Index
There was a significant improvement in DLQI during the study period. At baseline mean DLQI of the patients was 11.83 ± 4.97. After 4 weeks of treatment with bilastine 20 mg, there was a significant reduction in mean DLQI score (2.15 ± 2.68; P < 0.0001). All the patients showed a general decrease in the DLQI score, with statistically significant reductions in the overall score for both; week 2 (percentage reduction 50.2%, absolute mean reduction 5.94 points) and week 4 (81.82%, 9.68 points) with respect to the baseline assessment [Figure 5]. By disease groups, these differences were also statistically significant (P < 0.001 for each group at weeks 2 and 4), with reductions in DLQI as shown in [Table 3] and [Figure 6].
|Table 3: DLQI: absolute mean reduction in points and percentage reduction in different disorders at week 2 and 4|
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The change in 5D itch score correlated strongly with the change in DLQI in all subjects (r = 0.6, P < 0.0001) at the end of therapy. Moreover, it was found that bilastine was statistically significant in reducing pruritus associated with dermatophytosis eczema and psoriasis as compared to CSU and lichen planus as shown in [Table 4].
Overall bilastine was well tolerated. Only five (4.31%) patients complained of adverse events; sedation being the commonest (n = 2) followed by Fatigue (n = 1), dizziness (n = 1), and headache (n = 1) as shown in [Figure 7]. All the adverse events were mild in nature and none of the patients discontinued the treatment.
| Discussion|| |
We conducted this prospective, interventional, open-label, multicenter study to evaluate the effectiveness and safety of once-daily administration of bilastine 20 mg for 4 weeks in patients with pruritus associated with skin diseases. To the best of our knowledge, this is the first kind of study to evaluate the effectiveness and safety of bilastine in Indian patients in pruritus associated with skin diseases with 5D itch scale in India.
There are many scores like 5D itch scale, 4-item questionnaire, itch severity scale, pruritus grading system which calculate intensity of itch but we selected 5D itch scale. The 5D is a new tool and has demonstrated ease of use, content validity, test-retest reliability, internal consistency and ability to detect change in itch over time in patients with skin disease and systemic diseases.
In our study, treatment with bilastine for 4 weeks produced a statistically significant improvement in the effectiveness endpoint, that is, percentage of patients showing improvement and change in the weekly pruritus severity score from baseline in all patients and in each disease group. This improvement was supported by results at week 2, which also showed highly significant reductions from baseline. Furthermore, highest rates of improvement were found in the eczema group followed by the dermatophytosis group. Additionally, DLQI for pruritus also showed the same reduction profile and a statistically significant improvement over 4 weeks.
Bilastine is approved for CSU and allergic rhinitis.. But being anti-histamine, it is quite commonly used in pruritus associated with systemic and skin disorders. In our study, we considered many skin disorders which were associated with pruritus. There are some studies that were done on eczema and prurigo but for other disorders like dermatophytosis, psoriasis, and lichen planus; there was a scarcity of the reports
In our study, we found that about 35% of the patients achieved improvement in CSU group. These results were in contradiction with results of some other real-world studies where almost 73% - 83% of patients showed improvement.,. The result for eczema was similar to those found in a recent study conducted in Japanese patients with the same disease groups, which reported significant improvement with bilastine 20 mg for 52 weeks. Additionally, a significant reduced itch score was demonstrated as early as 2 weeks and efficacy was maintained throughout the study period. Similarly, another recently published study on bilastine in pruritus associated with skin disorders also reported a significant improvement in eczema group in 8 weeks. In our study, bilastine was found to be effective for pruritus related to skin diseases such as dermatophytosis and other chronic dermatoses and thus might be an effective adjunct to the treatment, in addition to primary medications
All disease groups treated with bilastine showed significant improvement in QoL at weeks 2 and 4. The mean reduction in DLQI score at week 4 for all patients was 9.68. It is in line with recently published study by Serra et al. which demonstrated similar results. Moreover, these results were clinically relevant as recommendations by Shikiar et al., who concluded that minimal important difference (MID) for the DLQI in the range of 2.24 to 3.10 was recommended in interpreting results for patients with chronic idiopathic urticaria. In common with these results, two recent studies of bilastine also demonstrated that bilastine produced significant improvements in QoL assessed by DLQI.,
The safety profile of bilastine was good with a low rate of AEs (4.31% of patients). The most frequent AEs reported during the study was sedation (1.72%) followed by headache, dizziness, and fatigue in one patient each (0.86%). All AE were mild in intensity and did not require any modification. These results were in line with recently published Japanese study.
In conclusion, bilastine has demonstrated efficacy for the relief of pruritus associated with disorders, with a very good safety profile. Additionally, we used 5D itch scale which was found to be reliable and with multidimensional measure. Amongst all diseases, bilastine was found to be more efficacious in dermatophytosis and eczema group than other groups suggesting its efficacy in these diseases. These exploratory findings flag the way for future studies with bilastine in these diseases, independent of baseline condition.
Financial support and sponsorship
This clinical study was carried out with unrestricted grant from Glenmark Pharmaceuticals Limited.
Conflicts of interest
Dr. Dhiraj Dhoot and Dr. Gaurav Deshmukh are employees of Glenmark Pharmaceuticals Ltd. Rest of authors do not have any conflict of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]