Clinical Use of Super-Bioavailable Itraconazole for the Management of Dermatophytosis: Consensus Statement by Dermatologists from India via the Modified Delphi Technique.

Super-bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as interindividual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50 mg and the USA as 65 mg and in India as 50 mg, 65 mg, 100 mg, and 130 mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis are insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. Sixteen dermatologists (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ), formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130 mg once daily and if not tolerated, 65 mg twice daily. The preferred duration for treating naïve dermatophytosis is 4-6 weeks and that for recalcitrant dermatophytosis is 6-8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. Expert clinicians reported that the overall clinical experience with SB ITZ was better than that with CITZ.

Comparative Efficacy and Safety of Super-Bioavailable Itraconazole-130 mg Once Daily in Obese and Non-Obese Patients of Glabrous Tinea.

Background: Obesity is considered one of the risk factors for dermatophytosis and warrants systemic therapy. Itraconazole is the most commonly used antifungal, but owing to pharmacokinetic challenges, super-bioavailable itraconazole (SITZ) was approved globally, recently. For the management of dermatophytosis in obese patients, there are mixed opinions regarding the dosing of systemic antifungals. Materials and Methods: This study was conducted to compare the efficacy and safety of SITZ-130 mg once daily in glabrous tinea or dermatophytosis in obese and non-obese patients for a total duration of 10 weeks on 87 eligible patients. Efficacy and safety assessments were done at weeks 3 and 6 with follow-up at week 10 for relapse. The primary objective was to assess the proportion of patients achieving complete cure at week 6 with the assessment of safety, clinical, and mycological cure rates as secondary objectives. Results: Out of 87 patients, 80 were considered for analysis. At week 6, 22/35 (63%) and 33/45 (73%) patients in obese and non-obese groups were completely cured (P = 0.47). Similarly, there was no statistically significant difference for mycological and clinical cure in both the groups (P = 0.17 and P = 0.61, respectively). Four patients in the obese group (18% of completely cured), while one patient in the non-obese group (3% of completely cured), relapsed within 4 weeks of completion of treatment (P = 0.14). The therapy was well tolerated by both groups, with only one patient in the non-obese group experiencing pruritus. Conclusion: SITZ-130 mg once daily achieved desired and similar clinical response in obese patients as of non-obese patients suffering from dermatophytosis, and hence, a higher dose may not require in obesity.

Comparative Clinical Study Evaluating the Efficacy and Safety of Topical 5% Cetosomal Minoxidil and Topical 5% Alcohol-Based Minoxidil Solutions for the Treatment of Androgenetic Alopecia in Indian Men.

Introduction Patients with androgenetic alopecia (AGA), who use alcohol-based topical minoxidil solutions, frequently experience localized irritation, dryness, and scalp redness. In this study, we compared the safety and effectiveness of topical 5% cetosomal minoxidil solution to those of topical 5% alcohol-based minoxidil solution in Indian men with AGA. Methods In this randomized, open-label study, male patients with AGA were randomized 1:1 to receive either solutions twice daily for 16 weeks. Efficacy endpoints included changes in basic and specific (BASP) grading, improvement in the trichoscopy score, and global photography at week 16 from baseline, whereas safety was evaluated by adverse events reported by patients and hair-related quality of life (QoL) using the Hairdex-29 questionnaire. Results Of the 80 patients, only 40 completed the study and were considered for complete analysis. Twelve out of 23 patients (52%) in the cetosomal minoxidil group and four out of 17 patients (24%) in the alcohol-based minoxidil group showed a positive increase in hair growth according to the trichoscopy score (p=0.1). According to the BASP grading system, nine patients (39%) and five patients (29%) in the cetosomal and alcohol-based minoxidil groups, respectively, showed improvement (p=0.73). Similarly, 19 (83%) and 10 (59%) patients in the cetosomal and alcohol-based minoxidil groups, respectively, reported positive hair growth on the global photography assessment (p=0.15). All the patients tolerated the treatment well, with no discontinuation in either group. There were four adverse events in the cetosomal minoxidil group, reported by two (9%) patients, whereas in the alcohol-based minoxidil group, 10 adverse events were reported by seven (41%) patients (p=0.02). In addition, the mean Hairdex-29 score of 40.26±4.71 at baseline improved to 32.32±3.35 in the cetosomal group, whereas it improved to 34.64±3.41 from 39.64±4.98 in the other group (p=0.03). Conclusions The 5% cetosomal minoxidil group showed improved safety but similar efficacy when administered twice daily. Therefore, cetosomal minoxidil may be a better option for treating AGA in males who are sensitive or nontolerant to alcoholic formulations.

A Prospective, Randomized, Comparative Study of Topical Minocycline Gel 4% with Topical Clindamycin Phosphate Gel 1% in Indian Patients with Acne Vulgaris.

Acne vulgaris is characterized by inflammatory and non-inflammatory skin lesions with a high prevalence among adolescents in India. Not enough studies are reported on the use of topical antibiotics for the management of acne in the Indian population. The proposed study aims to compare the efficacy and safety of topical minocycline gel 4% with topical clindamycin gel 1% in the Indian population. A randomized, open-label, double-arm study was planned at two centers in India. One hundred patients were enrolled and randomized equally to two treatment arms. The drugs were applied once daily, preferably at the same time each day. The number of inflammatory and non-inflammatory lesions, as well as the investigator's global assessment (IGA), were obtained at the baseline and on weeks 3, 6, 9, and 12. The change in these parameters from baseline to week 12 was compared between the two treatment arms. A tolerability assessment was also performed on selected parameters. The age of patients ranged between 14 and 31 years, with female preponderance in each arm. On week 12, the percent change in inflammatory and non-inflammatory lesions in the minocycline 4% arm was significantly higher than in the clindamycin 1% arm (p < 0.0001). The IGA treatment success was significantly higher in the minocycline arm compared to the clindamycin arm on weeks 9 and 12, with p-values of 0.001 and 0.015, respectively. Tolerability assessment revealed significantly improved parameter performance in the minocycline arm compared to the clindamycin arm. On subgroup analysis, in adolescents, minocycline was found to be more efficacious than clindamycin. The comparative assessment resulted in a significantly improved performance of minocycline gel 4% compared to clindamycin gel 1% in the Indian population, thus making it a preferred choice for the treatment of moderate-to-severe acne in India.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

Real-World Effectiveness, Safety, and Tolerability of Cetosomal Minoxidil 5% Alone and a Fixed Drug Combination of Cetosomal Minoxidil 5% With Finasteride 0.1% in the Management of Androgenetic Alopecia (Inbilt Study).

Introduction Topical minoxidil 5% is a widely used medication in the treatment of androgenetic alopecia (AGA) but is usually associated with adverse events (AE) such as scalp irritation, dryness, and itching. This prompted the development of nonalcoholic solutions, and cetosomal minoxidil was the most recent one. Methods Retrospective multicenter data analysis was conducted at 66 centers across India for adult AGA patients. Patients treated with either cetosomal minoxidil 5% alone (Group I) or a fixed drug combination of cetosomal minoxidil 5% and finasteride 0.1% (Group II) were analyzed for the effectiveness and safety of either formulation. The Physician Global Assessment (PGA) and Patient Global Assessment (PtGA) were used to assess each treatment's effectiveness. Safety was reported by records of AE and a product tolerability assessment with subjective cosmetic acceptability as recorded by physicians. Results Of the 261 patients, 132 were in Group I, and 129 were in Group II. At 16 weeks, in PGA, mild to moderate improvement was noted in 48% and 32% of patients in Groups I and II, respectively, whereas significant to excellent improvement was seen in 52% and 68% of patients in Groups I and II, respectively. Similar results were noted for PtGA. In Group I, 64% of patients rated the product's tolerability as excellent, and 69% reported the same in Group II. Meanwhile, 64% of patients in Group I and 74% in Group II rated the product as excellent in subjective cosmetic acceptability. Conclusions From real-world analysis, cetosomal-based minoxidil solutions were found to be effective and tolerable in AGA and could serve as therapeutic alternatives to alcoholic formulations for AGA management.

Management of Dermatophytosis: Real-World Indian Perspective.

Background: In spite of the availability of multiple consensus statements on dermatophytosis management, different treatment approaches have been experienced in India and require more scrutiny to further update guidelines and improve patient care. Aim: To determine the different approaches in dermatophytosis diagnosis and management among dermatologists in India. Materials and Methods: A web-based questionnaire was created and validated by five panelists with experience of >15 years in dermatophytosis and then circulated to about 2,000 dermatologists in India in September 2021 for a real-world management scenario. Results: Out of 2,000 dermatologists, 459 responded. About half of the dermatologists (51%) routinely conduct potassium hydroxide mount (KOH) at the initiation of therapy. Similarly, about 53% of dermatologists initiate the management of dermatophytosis with combination therapy in all types of dermatophytosis for 4-6 weeks depending upon severity. Different types of combinations are being practiced, such as either two systemic and one topical, two topicals and one systemic, but the combination of one systemic and one topical (69%) is the most commonly practiced. Itraconazole (100 mg twice a day) and luliconazole are the most commonly prescribed antifungal medications. In case of non-response to routine dose of systemic anti-fungals, about 72% of dermatologists up dose them. Most of them continue these drugs for additional 1-2 weeks after clearance of the disease. Additionally, keratolytics and moisturizers are commonly prescribed. Additionally, 62% advise liver function tests (LFTs) at the initiation of therapy, whereas 72% advise monitoring adverse effects due to systemic antifungal drugs during treatment. Conclusion: Combination therapy stood out as the need of the hour in the current menace of dermatophytosis with timely monitoring of laboratory tests for adverse events due to the use of systemic antifungals for a longer duration.

Comparative Efficacy of Super Bioavailable Itraconazole Capsules 50 mg vs 65 mg Twice Daily in the Management of Glabrous Tinea.

Introduction: Owing to pharmacokinetic challenges of itraconazole, super-bioavailable itraconazole (SB) was developed and recently approved in strengths of 50mg and 65mg. But comparative study was lacking between these two strengths in glabrous tinea (dermatophytosis) management. Hence, this study was planned to compare the efficacy of both these strengths in dermatophytosis. Methods: One hundred eligible patients were enrolled in this prospective, randomized, clinical study during May-2022 to September-2022 at tertiary hospital in Ahmedabad in adults. Efficacy and safety assessments were done at week-3 and 6 with follow up at week-10 for relapse. Primary objective was to assess the proportion of patients achieving complete cure at week-6 following treatment in both the groups. Secondary outcomes compared safety, clinical and mycological cure rates. Results: Of the 100 patients enrolled, 98 patients (50 in SB-50mg and 48 in SB-65mg group) included in the final analysis. At week 6, 20 patients (40%) and 30 patients (62.5%) achieved complete cure (p < 0.05) in SB-50mg and SB-65mg groups, respectively. In completely cured patients, relapse was reported in 3 (15%) and 5 (17%) patients of SB-50mg and SB-65mg groups, respectively (p = 1). A significant difference was noted in clearance of symptoms and lesions in SB-65mg group (p < 0.05). Moreover, similar results were also obtained in sub-group analysis of recalcitrant dermatophytosis. Both the treatments were found to be safe and well tolerated with no discontinuation. Conclusion: Study result concluded the superiority of SB-65mg over SB-50mg in terms of cure rate and resolution of symptoms in dermatophytosis management.

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study.

Background Obesity may alter tissue distribution and clearance of several drugs, especially lipophilic ones. Itraconazole, a lipophilic drug, has been recently introduced in a super-bioavailable formulation (SB-ITZ) for the treatment of dermatophytosis. Evidence regarding optimal dosing of SB-ITZ in obesity is lacking. A current experimental study was planned to analyze tissue concentrations of SB-ITZ at different doses in obese and non-obese rats.  Materials and methods Thirty-six Wistar albino rats of either sex were divided into obese and non-obese rats equally. Further, rats in both categories were divided into three dosing groups. Group 1 received SB-ITZ 13 mg once daily in the morning, group 2 received SB-ITZ 13 mg in the morning and 6.5 mg in the evening, while Group 3 rats received SB-ITZ 13 mg twice daily, orally. Concentrations of SB-ITZ in the skin, serum, and fatty tissue were assessed in each group on days 7, 14, 21, and 28. Comparison of SB-ITZ concentrations in various tissues in obese and non-obese rats and inter-group comparison of tissue concentrations across the three dosing regimens was done at day 28 and expressed as Mean ± SD.36 Wistar rats were divided into obese and non-obese rats equally. Results At day 28, skin concentrations of SB-ITZ were 5.36±1.1, 8.9±1.7 and 10.13±1.7 µg/g in Groups 1, 2, and 3, respectively, in non-obese rats, which was statistically significant (p<0.05) than skin concentration of obese rats (2.72±0.6, 4.2±0.7 and 4.66±0.5 µg/g) for the corresponding dosing groups respectively. Skin concentration of SB-ITZ was statistically significant for Groups 2 and 3 as compared to Group 1. Still, no statistically significant difference was noted between Groups 2 and 3 in non-obese and obese rats. Fatty tissue concentration of SB-ITZ was comparable in all 3 dosing regimens in non-obese and obese rats. But on the intergroup comparison, a statistically significant difference was observed for Groups 2 and 3 against Group 1 (p<0.05). Increasing the dose of SB-ITZ increased serum concentration. In non-obese rats, a statistically significant difference was noted between Group 2 (74.33±6.6 ng/ml) and Group 1 (52.5±9.9 ng/ml); p<0.01 and also in Group 3 (81.33±6.8 ng/ml) against Group 1; p<0.01. Group 3 achieved significantly higher concentration than the other two groups in obese rats (Group 3; 72±5.3, Group 2; 60.5±4.3, and Group 1; 45±7 ng/ml; p<0.01). Conclusion Overall, skin, fatty tissue, and serum concentrations of SB-ITZ were higher in non-obese rats compared to obese rats in all three dosing groups. Moreover, skin and fatty tissue concentrations were proportionately higher than serum in all the groups in non-obese and obese rats. Though the skin concentration of non-obese rats was significantly higher than obese rats, skin concentration in obese rats was within the minimum inhibitory concentration (MIC) range, demonstrating the efficacy of all dosing regimens.

Pharmacokinetic and clinical comparison of super-bioavailable itraconazole and conventional itraconazole at different dosing in dermatophytosis.

Background: Due to changing face of dermatophytosis in India, many dermatologists practice different dosing patterns of itraconazole (ITZ). Recently, a new form of ITZ, super-bioavailable ITZ (SBITZ), has been commercialized to overcome the pharmacokinetic challenges of conventional ITZ (CITZ). Serum and sebum concentration of ITZ plays an important role in the management of dermatophytosis. Hence, the current study compares the rate and extent of serum and sebum concentration of SBITZ and CITZ at different dosing to determine their efficacy and safety in patients with dermatophytosis. Methods: This was an open-label, randomized, four-arm study including 40 adult patients diagnosed with glabrous tinea who were randomized equally into four groups to receive either CITZ-100-BD or CITZ-200-OD (2×100 mg capsules) or SBITZ-130-OD or SBITZ-100-OD (2×SBITZ-50 mg capsules) for 4 weeks. Serum and sebum samples were analysed at different time intervals along with clinical efficacy and safety. Results: For serum concentration, on day 28, the arithmetic mean and standard deviation (SD) for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB100-OD were 1262±233.5 ng/mL, 1704±261.6 ng/mL, 1770±268.9 ng/mL and 1520±231.7 ng/mL, respectively, which was statistically significant for OD dosing of ITZ/SBITZ over CITZ-100-BD. Similarly, for sebum concentration, the arithmetic mean and SD for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB-100-OD were 1042±163.45 ng/mg, 1423±192.46 ng/mg, 1534±227.55 ng/mg and 1107±182.35 ng/mg, respectively, which was statistically significant for SB-130-OD and CITZ-200-OD over CITZ-100-BD and SBITZ-100-OD dosing. No significant difference was noted between SBITZ-130 and CITZ-200 (p=0.25). Only two patients achieved complete cure in the SBITZ-130 group, whereas no patients achieved the same in other groups (p=0.47). All the dosages were very well tolerated with only 12 adverse events reported by ten patients in all groups. Conclusion: All formulations achieved desired serum and sebum concentrations required for efficacy in dermatophytosis, but SB 130 mg OD and CITZ 200 mg OD were statistically significant than other ITZ doses in achieving sebum concentration. Additionally, SBITZ 130 mg OD was bioequivalent to CITZ 200 mg OD and achieved similar results to those of CITZ 200 mg OD but at 35% lower drug concentrations.

Real-World Indian Experience of Switchover to Bilastine 40 mg/day in CSU Patient Refractory to Other Antihistamines at Double Dose.

Background: Although second-generation antihistamines (SGAHs) are recommended as first-line drugs in chronic spontaneous urticaria (CSU), symptom relief has been reported in <50% of patients at licensed doses and up to fourfold dosing is recommended for these patients. Bilastine (SGAH), at licensed doses and higher doses, is efficacious in CSU. However, large-scale real-world data is scarce. Objectives: To report the real-world evidence of the safety and effectiveness of bilastine at a double dose (40-mg per day) in CSU management. Materials and Methods: In this retrospective questionnaire-based study carried out from February 2022 to July 2022, a pre-validated questionnaire was used to gather data on patients with CSU in dermatology practice from 62 centres across India. Adult patients of either gender diagnosed with CSU and switched over to bilastine 40 mg/day due to a non-satisfactory response (UCT score <12) to other antihistamines at double dose were considered for analysis. Based on UCT scores, patients were classified as responders (UCT ≥12) and non-responders at follow-up assessment at 2 weeks as compared to baseline. Results: 177 patients with a mean disease duration of 2.11 ± 1.48 years were included in the final analysis, with 53% females and 47% males. At the end of two weeks, 74/177 (42%) patients were classified as responders, and 103/177 (58%) were non-responders to Bilastine 40 mg/day. The mean change of UCT score from 5.0 ± 2.2 at baseline to 8.08 ± 5.41 (62% improvement) was significant (P < 0.001). Sedation was reported by ten patients without any discontinuation of treatment. Conclusion: Bilastine 40 mg/day was effective and well-tolerated in controlling CSU symptoms refractory to antihistamines at double doses.

Intermittent or Sequential Topical Tacrolimus in Atopic Dermatitis: Systematic Review and Meta-Analysis.

Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an immunomodulator), belongs to the class of calcineurin inhibitors, with promising efficacy in AD. We performed this systematic review to obtain an up-to-date coverage map of controlled clinical trials of sequential or intermittent treatments with TCI as a therapeutic intervention for AD. Articles of interest were retrieved from PubMed, Google Scholar, and EMBASE published between between January 2000 and March 2023. Key words were "calcineurin inhibitors," "corticosteroids," "atopic dermatitis," "pruritus," "sequential," "intermittent" and "consecutive" while fixed language search consisted of "Intermittent topical calcineurin inhibitors AND topical corticosteroids AND atopic dermatitis OR eczema" AD patients who were administered sequential and/or intermittent applications of TCI for management of atopic eczema were included. Outcome measures included but were not limited to Scoring of Atopic Dermatitis (SCORAD) and the Eczema Area Severity Score (EASI). Four clinical trials were considered for the purpose of review. A total of 101 patients with AD were analysed. The risk of bias was low in two studies, while the other two had an unclear risk of bias. Overall, pooled data from two trials revealed that sequential therapy with TCS/TCI was comparable to monotherapy or emollients, as the test for overall effect determined was non-significant with a p-value of 0.33. The two studies were highly heterogeneous, as indicated by a very high I2 of 92% and an extremely significant p-value (p=0.0005). Sequential therapy with TCS and TCIs was effective and well tolerated in the management of AD and it may be considered an important treatment approach during the initial period.

Evaluation of the Efficacy and Safety of Apremilast in the Management of Lichen Planus.

Introduction: Lichen planus is a chronic disease with often disappointing and less than optimal treatment options. Apremilast modulates inflammatory signalling pathways which play a central role in the pathogenesis of lichen planus, thus making it useful in the management of such patients. Materials and Methods: The present study was an investigator-initiated, single-centre, non-randomized, open-label, pilot study of the efficacy and safety of Apremilast in the treatment of lichen planus. All the patients were prescribed Apremilast 30mg, twice daily, for 12 weeks. Patients were evaluated for improvement in their lesions, based on the physician's global assessment (PGA), subject global assessment (SGA), and target area lesion symptom score (TALSS). Results: A total of 34 patients were included in the study; 26 patients completed the study duration and were considered for the final analysis. After 12 weeks, 34.61% (n = 9/26) patients showed 2 or more grade improvement in their disease as per PGA. About 42.30% (n = 11/26) patients achieved more than 50% improvement in their lesions based on the subject global assessment of their disease. There was a significant improvement in TALSS during the study period (p < 0.0001). Only 23.07% (n = 6/26) patients developed one or more adverse events because of Apremilast with headache being the commonest side effect. Conclusion: The results obtained in our study justify that Apremilast is efficacious and safe in the management of patients with lichen planus. Based on these results, Apremilast can be considered as a promising alternative treatment option in patients with lichen planus.

An Open-Label, Randomized, Prospective, Comparative, Three-Arm Clinical Trial to Evaluate the Safety and Effectiveness of Apremilast with Three Different Titration Methods in Patients with Chronic Plaque Psoriasis in India.

Purpose: To minimize adverse effects (AEs), apremilast is recommended to titrate at the initiation of therapy. But still, many patients experience AEs, resulting in discontinuation of therapy. As a result, many dermatologists have adapted to further titrate apremilast in different ways. The present study was planned to evaluate the safety and effectiveness of apremilast in different dose titration methods as initiation therapy in the treatment of plaque psoriasis. Patients and Methods: In this open-label, randomized, prospective, comparative, three-arm, single center study, 128 plaque psoriasis patients were included. Patients were randomized into three groups. Group I received standard titration for the first 6 days; Group II received all tablets in a starter pack as once a day (OD) total for 13 days; and Group III received two starter packs as 8 tablets each of apremilast 10 mg and 20 mg as OD and 10 tablets of 30 mg as OD, in total for 26 days. All groups received apremilast 30 mg as twice a day after initial titration. The total duration of apremilast therapy in all groups was 16 weeks. Results: In safety assessment, AEs were reported in 50%, 41.3% and 25% in Groups I, II and III, respectively (p <0.05) with nausea being the most common AE. In Group I, 10.53% of patients discontinued apremilast whereas 6.52% and 2.27% discontinued in Groups II and III respectively. Maximum number of AEs were seen in Group I in first week only (74.19%) compared with other groups. At week 16, on the Psoriasis Area and Severity Index, PASI 75 was achieved in 31.43%, 42.4% and 33.3% of patients in Groups I, II and III, respectively with no statistical difference between any groups. Conclusion: It can be concluded that slower titration is a useful strategy for minimizing AEs while at the same time maintaining effectiveness of apremilast.

A Comparative, Three-Arm, Randomized Clinical Trial to Evaluate the Effectiveness and Tolerability of Bilastine vs Fexofenadine vs Levocetirizine at the Standard Dose and Bilastine vs Fexofenadine at Higher Than the Standard Dose (Up-Dosing) vs Levocetirizine and Hydroxyzine (in Combination) in Patients with Chronic Spontaneous Urticaria.

INTRODUCTION: Though second-generation antihistamines (SGAH) are first-line drugs in chronic spontaneous urticaria (CSU), 50% of patients do not respond to them. In such patients, guidelines recommend either up-dosing of SGAH or combination of different antihistamines. However, the studies comparing these treatment regimens are limited. METHODS: In this comparative, three-arm study, CSU patients were randomized to receive standard dose of either bilastine, fexofenadine, or levocetirizine for 2 weeks. After 2 weeks of treatment, non-responders received double dose of either bilastine or fexofenadine, while hydroxyzine 25 mg once daily was added in the levocetirizine group. Patients were primarily evaluated for improvement in CSU, quality of life, and somnolence. RESULTS: A total of 110 patients with CSU were recruited. At the end of 4 weeks, 33/39, 26/35, and 22/36 patients in the bilastine, fexofenadine, and levocetirizine groups showed improvement in urticaria symptoms. At week 2, there was no statistical difference in urticaria activity score (UAS7) improvement between any of the groups; however, at week 4, there was a statistical difference between the bilastine and levocetirizine groups (p<0.05). Somnolence was significantly lower in the bilastine group (p<0.05). Bilastine was statistically significant (p<0.05) in the improvement of quality of life as compared to both groups. No major adverse events were reported during study period; however, bilastine was associated with significantly lower levels of AEs compared to levocetirizine (p<0.05). CONCLUSION: Two-fold up-dosing of bilastine improves CSU symptoms without compromising safety as compared to two-fold up-dosing of fexofenadine and combination of first- and second-generation antihistamines.

Prospective, Open-Label, Multi-Centre, Randomized Study to Compare the Effectiveness, Safety, and Tolerability of Lulican™ Shampoo Versus Ketoconazole Shampoo in Indian Adult Patients With Mild to Moderate Scalp Seborrheic Dermatitis (LEAD Study).

Introduction Although seborrheic dermatitis (SD) is not lethal, it has a significant impact on the quality of life. Many cases of SD are managed with ketoconazole, but luliconazole has shown an equivalent or lower minimum inhibitory concentration (MIC), but not many studies have been done for its efficacy and safety in SD. With this in mind, we set out to conduct a study comparing the effectiveness, safety, and tolerability of Lulican™ (luliconazole 1% + salicylic acid 3% + ZPTO 1%) shampoo and Ketoconazole (Ketoconazole 2% + ZPTO 1%) shampoo in the treatment of SD. Materials and methods In this prospective, randomized, multi-center study, mild to moderate scalp SD patients were prescribed Lulican™ or Ketoconazole shampoo three times a week for a duration of four weeks. Effectiveness assessment was done with the Seborrheic-Dermatitis-Severity-Score (SDSS) and Physician-Global-Assessment (PGA), and quality of life was assessed with the help of the Scalpdex-23 questionnaire. Results At four weeks, 68% and 57.9% reduction was seen in SDSS in Lulican™ and Ketoconazole shampoo, respectively. Moreover, 58% and 44% of patients achieved excellent to moderate responses as per PGA with Lulican™ and ketoconazole shampoo, respectively. For safety, no statistical difference was reported, but product tolerability and subjective cosmetic acceptability were significantly better in the Lulican™ group as compared to the Ketoconazole group at the end of four weeks. The mean Scalpdex-23 score at week four was reduced by 35.7% and 21.1% in Lulican™ and ketoconazole groups, respectively (p<0.05). Conclusion While both treatments were successful in alleviating SD symptoms and were well tolerated, Lulican™ stood out as a preferred treatment option due to better quality of life (QoL) improvement in SD.

An Open-Label, Randomized, Double-Arm Clinical Trial to Compare the Effectiveness and Safety of Super Bioavailable Itraconazole Capsules and Itraconazole Capsules in the Management of Dermatophytosis in India.

PURPOSE: A new oral formulation of itraconazole, called super bioavailable itraconazole (SBITZ), has been launched in India, exhibiting greater bioavailability than conventional itraconazole (CITZ). No clinical studies on its effectiveness and safety in dermatophytosis in comparison with CITZ have been conducted in India. Hence, the aim of this clinical study was to compare the effectiveness and safety of SBITZ capsules and CITZ capsules in dermatophytosis. PATIENTS AND METHODS: This was an open-label, randomized, double-arm clinical study in which 70 patients (≥18 years of age) of either gender and diagnosed with tinea cruris, tinea corporis, and/or tinea faciei were included. The study was divided into two parts, the first part comprising a treatment period of 4 weeks and the second part an observation period for recurrence, comprised of another 4 weeks, thus making an entire study duration of 8 weeks. RESULTS: Of the 70 patients enrolled in this study, 59 (33 patients in the CITZ group and 26 patients in the SBITZ group) were included in the final analysis. In both groups, most patients were diagnosed with tinea cruris et corporis, with five or more lesions. At week 4, 11 patients (33.33%) and 17 patients (65.38%) had achieved complete cure (p<0.05), whereas 22 patients (66.67%) and 22 patients (84.61%) had achieved mycological cure (p=0.14), in the CITZ and SBITZ groups, respectively. During the observation period, recurrence was seen in 1/11 and 4/17 completely cured patients in the CITZ and SBITZ groups, respectively (p=0.15). A significant difference was noted in resolution of symptoms as well as lesions of dermatophytosis in the SBITZ group (p<0.05). Both treatments were found to be safe and well tolerated. CONCLUSION: In the light of real-world evidence on effectiveness and safety, SBITZ should be considered as a potent therapeutic choice to effectively control the current menace of dermatophytosis in India.

Real-Life Experience of Efficacy and Safety of Bilastine in the Refractory Cases of Chronic Spontaneous Urticaria and its Effect on the Quality of Life of Patients.

INTRODUCTION: Second-generation H1-antihistamines (SGAHs) are the mainstay of treatment of chronic spontaneous urticaria (CSU). Bilastine, newer non-sedating SGAHs, was recently introduced in India after the approval of the Drugs Controller General of India. There is a paucity of evidence about the long-term efficacy and safety of Bilastine in Indian patients. We undertook this study to find the long-term efficacy and tolerability of Bilastine in patients with CSU in India. MATERIALS AND METHODS: This retrospective chart analysis was conducted by analyzing electronic medical records from May 1, 2019, to March 20, 2020, to identify patients of CSU who were prescribed Bilastine. Adult patients, with CSU >6 months were included, who had an unsatisfactory response as per Urticaria Activity Score 7 (UAS7) to previous antihistamine therapies, and who continued treatment for at least 6 months were included. Treatment effectiveness was determined by retrospectively reviewing their UAS7 scores from their medical records and evaluating their scores at weeks 4, 8, 12, 16, 20, and 24. Also, DLQI was assessed and compared at baseline and week 24. RESULT: Forty-nine patients were found to fulfill the criteria and included in the study. At the end of 24 weeks, 51% of patients (n = 25) achieved complete treatment response (UAS = 0), whereas 49% of patients (n = 24) were labeled as well-controlled urticaria (UAS<6). At 24 weeks, the mean UAS7 score (1.35 ± 1.61) was statistically significant compared to the baseline score (20.2 ± 5.73). The mean score of DLQI was also reduced to 1.63 ± 1.18 at 24 weeks from 8.39 ± 2.49 at baseline (P-value <0.001). CONCLUSION: The study showed that in patients who had an inadequate response with commonly used antihistamines at a double dose or combined use, switching over to Bilastine resulted not only in relieving the symptoms of CSU but also improved the quality of life of the patients with CSU.

Real-World Insight on Apremilast Therapy in Patients with Plaque Psoriasis: Indian Experience.

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disorder, which follows a chronic course. Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor, approved by US-FDA for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. A majority of the data related to the effectivity and safety of apremilast use in psoriasis is extracted from clinical trials. The present study was planned to get an insight into real-world experience with the use of apremilast in patients with moderate-to-severe plaque psoriasis related to its effectiveness and safety in India. MATERIALS AND METHODS: The present study was a retrospective one, wherein a review of the medical records of patients with psoriasis was conducted at one center in Kolkata, who were prescribed apremilast for 16 weeks in a community dermatology practice, from December 2017 to May 2018. RESULTS: Out of 39 patients, two patients discontinued treatment due to diarrhea. Only three patients were treatment naïve; the rest had taken some form of systemic therapy before apremilast. At the end of 16 weeks of treatment with apremilast, PASI 100 was achieved in one patient (2.7%), PASI 90 in one (2.7%), PASI 75 in 18 patients (48%), while 14 patients (38%) achieved PASI 50. Eighteen (46%) experienced adverse events, diarrhea being the most common (29.7%). CONCLUSION: The findings of the present study indicate that apremilast is effective in a real-world setting, as compared with clinical trials in achieving certain endpoints like PASI 75, as was found in other real-world studies in other countries, as well.