An Open-Label Pilot Study to Investigate Safety and Efficacy of Fixed Combination Tazarotene 0.045% and Halobetasol Propionate 0.01% Lotion for the Treatment of Scalp Psoriasis

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INTRODUCTION

Psoriasis is a common, chronic, autoimmune skin disorder that, in its plaque form, is characterized by dry, red lesions with silvery scales that cause itching, dryness, and irritation.1 About 80% of psoriasis patients have scalp involvement, which can be challenging to treat. Systemic therapies, including biologics, may improve scalp psoriasis, although there is limited head-to-head comparative data assessing the effectiveness of biologics for scalp disease.2,3 Additionally, not all patients are candidates for systemic therapy, and dermatology providers may not consider systemic therapy for patients with psoriasis limited primarily or exclusively to the scalp. Other treatments shown effective in the management of scalp psoriasis include phototherapy, topical medications, and even complementary and alternative medical interventions used to clear psoriasis or reduce symptoms; combination approaches are frequently employed.4-7 These psoriasis treatment methods have been used with limited to moderate results for scalp involvement due to challenges associated with application, potential adverse effects, and high costs.8,9 Topical products are difficult to use consistently to treat scalp psoriasis, especially due to hair on the affected area; application of topical medications can be arduous, messy, and inconvenient and can leave residue on the scalp and hair.5 Long-term adherence with inconvenient regimens may be limited, leading to poor response or frequent relapse.9,10 Importantly, it is recognized that scalp psoriasis can have a detrimental psychological impact upon patients, with many experiencing interpersonal stress and anxiety over displaying their symptoms publicly.11,12 Therefore, it is desirable to identify effective interventions for scalp psoriasis.

Fixed combination tazarotene 0.045% and halobetasol propionate 0.01% (Duobrii, Ortho Dermatologics) lotion has recently been approved for treatment of moderate-to-severe plaque type psoriasis. The lotion base is suggested to confer benefits for application to the hair-bearing scalp. A pilot study was completed to evaluate the efficacy and safety of fixed combination tazarotene 0.045% and halobetasol propionate 0.01% for the treatment of moderate to severe plaque psoriasis with scalp involvement. There was significant improvement in the primary and most secondary endpoints, indicating that further study is warranted.

STUDY DESIGN

A single-center, open-label pilot study was designed to assess treatment with fixed combination tazarotene 0.045% and halobetasol propionate 0.01% lotion in adult subjects (age 18 or older) with moderate-to-severe plaque type, as indicated by an Investigator’s Global Assessment (IGA) scale value of 3 or 4, with scalp involvement.

Subjects were provided study medication and instructed to apply the supplied formulation to all affected areas once daily and rub in gently and completely. The study duration was 12 weeks, with scheduled visits for screening at baseline, at week 4, week 8, and week 12 (end of study (EOS]). The study protocol was Institutional Review Board (IRB)-approved. The site carried out the study in keeping with local legal and regulatory requirements, abided by principles defined in the recognized “Guideline for Good Clinical Practice,” and strictly followed ethical principles described in the current version of the Declaration of Helsinki.

Inclusion/Exclusion Criteria
The study enrolled adult subjects (≥18 years of age) of either gender. Females of child-bearing potential were required to have a negative urine pregnancy test within 7 days of the first dose of study drug and had to agree to practice a reliable method of contraception throughout the study. Subjects had to have moderate to severe overall psoriasis as well as moderate to severe scalp psoriasis to be included.

Subjects with spontaneously improving or rapidly deteriorating plaque psoriasis, as determined by the investigator, and those with guttate, erythrodermic, or pustular psoriasis were ineligible for enrollment. Additionally, subjects were not eligible for enrollment if they had used topical steroids, topical immunomodulators, topical vitamin D derivatives, tar, salicylic acid, anthralin, or any other topical treatment for scalp psoriasis within 2 weeks of baseline, any biologics within 3 months of baseline, or other systemic psoriasis treatments (ie, oral retinoids, methotrexate, cyclosporine, or other immunomodulators) within 4 weeks of baseline. Subjects who had undergone treatment with UVB or PUVA within 2 weeks of baseline were also ineligible. Subjects with known hypersensitivity to study medication or any of its components were excluded.

Study Evaluations
At each visit, IGA, Investigator’s Global Assessment (sIGA), body surface area (BSA), Psoriasis Scalp Severity Index (PSSI), and physical examination, vital signs, prior and concurrent medications, tolerability and safety assessments, and urine pregnancy testing (where applicable) were performed. At baseline and week 4, drug dispensation was conducted, and at week 8, drug collection was conducted. Week 8 was the end of treatment and week 12 was the final visit for safety and maintenance after stopping the treatment at week 8.

The area of the body affected by psoriasis was estimated as a percentage of the subject’s total body surface area. As a means to standardize measurements, the area of the subject’s palm was considered as 1% of total BSA.

Efficacy Assessments
The primary endpoint is the percent of patients who are clear or almost clear on the investigator global assessment scale (IGA) at week 8.

Secondary endpoints include the percent of patients who are clear or almost clear on IGA at weeks 4 and 12; the percent of patients who achieved psoriasis scalp severity index (PSSI) 75 at weeks 4, 8, and 12; the body surface area assessment (BSA) improvement at weeks 4, 8, and 12; the scalp IGA (sIGA) improvement at weeks 4, 8, and 12; the visual analog score of pruritus (VAS) improvement at weeks 4, 8, and 12; local tolerability (itching, dryness, burning/stringing) at weeks 4, 8, and 12; and dermatology life quality index (DLQI) improvement at weeks 4, 8, and 12 were the secondary endpoints.

Subject compliance with the study treatment regimen was also assessed at each visit. Subjects complied with the restrictions based on prohibited medications and treatments as detailed in the exclusion criteria. The use of any concurrent medication, prescription or over-the-counter drug, was recorded along with the reason the medication was taken.

All subjects were monitored for adverse events (AEs), irrespective of causality.

Statistical Analysis
Statistical analyses were conducted on an intent-to-treat (ITT) population that included all subjects who were enrolled and received study medication. Due to the small sample size and exploratory nature of the study, descriptive statistics were performed using SAS. All statistical tests were two-sided and interpreted at a 5% significance level. Analyses of study treatment were performed using an ANCOVA technique with the baseline value as the covariate. Mean scores were also analyzed. Safety analyses were performed in terms of incidence and severity of local tolerance signs and symptoms and adverse and/or unexpected events.

RESULTS

A total of 21 subjects were included in the ITT data analysis. Of 21 patients enrolled in the study, 21 completed 8 weeks of therapy and 20 of 21 completed the 12-week follow-up visit. There were 12 males (57%) and 9 females (43%) enrolled, and 20 white (95%) and 1 African American (5%) subject. The average age at enrollment was 52 (SD = 17), with ages ranging from 24 to 86.

Treatment with fixed combination tazarotene 0.045% and halobetasol propionate 0.01% lotion resulted in significant reductions at each timepoint in the primary and most secondary outcome measures: the Investigator’s Global Assessment (IGA), Psoriasis Scalp Severity Index (PSSI), body surface area (BSA), scalp IGA (sIGA). There were significant improvements in itching at weeks 4 and 8, burning at week 12, and the DLQI at week 8. There were 7 adverse events in 5  individuals, none of which was serious or of ongoing concern.

IGA Primary Endpoint
There were significant decreases in IGA from baseline at weeks 4, 8, and 12. At week 8, 10 of 21 (48%) patients were clear or almost clear (P=.0006; CI 95%). By week 12, after treatment discontinuation, 40% of subjects remained clear or almost clear (P=.004; CI 95%).

Secondary Endpoints
There were significant absolute and relative decreases in PSSI at weeks 4, 8, and 12. At week 4, 43% of subjects achieved PSSI 75, and 67% achieved PSSI 75 at week 8. At week 12, 45% of subjects maintained PSSI 75. PSSI 90 was achieved by 38% of respondents at week 8 and 30% maintained at week 12. PSSI 100 was achieved by 29% of respondents at week 8 and 20% maintained at week 12 after stopping the treatment at week 8.

Significant changes in BSA involvement were seen. Average BSA involvement decreased by 31% at week 4 (P=.0002), 47% at week 8 (P=.0003), and 34% at week 12 (P=.007; Figure 3).

At week 8 visit, 15 of 21 (72%) patients were clear or almost clear on the scalp IGA (CI 95%; SD 48%, 88%) and 50% maintained at week 12. More importantly, 29% of the subjects had all clear scalp at week 8 and 20% maintained all clear scalp at week 12.

There were significant absolute and relative improvements in DLQI measures at Week 8 and a significant absolute decrease at week 12.

Mean VAS for pruritus scores were decreased at weeks 4, 8, and 12, compared to baseline. However, neither absolute nor relative reductions in VAS achieved statistical significance at any timepoint. Tolerability assessments revealed significant decreases in itching at weeks 4 and 8 and in burning at week 12. Severe itch was reported by 7 patients at baseline and only 2 at week 12; 1 of 3 patients who reported severe burning at baseline continued to have severe burning at week 12. No patients reported severe of dryness. There were no reported instances of skin atrophy, striae, telangiectasia, or folliculitis.

Seven adverse events (AE) occurred in 5 subjects. None were serious and none appeared to be related to study medication. These included upper respiratory infection (resolved), type 2 diabetes, bilateral ear infection, generalized poison ivy (resolved), intermittent acute vertigo of peripheral origin, generalized muscle weakness, and worsening of acne.

CONCLUSION

Scalp psoriasis is a significant concern for affected patients,
and treatment has remained challenging. Results of this pilot
study demonstrate that fixed combination tazarotene 0.045%
and halobetasol propionate 0.01% lotion is efficacious for the
treatment of scalp psoriasis in adults, based on significant
improvements in IGA, PSSI, BSA, sIGA, and DLQI. Treatment
improved symptoms of itch and was well-tolerated. The type,
frequency, and severity of AEs reported in this study suggest
the safety of the medication for the treatment of scalp psoriasis.
Additional studies are encouraged to further evaluate the use of
fixed combination tazarotene 0.045% and halobetasol propionate
0.01% lotion to treat psoriasis with scalp involvement.

DISCLOSURES

Dr. Kircik has received either grant or honoraria compensation as either Speaker, Consultant, Investigator, or Advisory Board member for Abbott Laboratories, Abbvie, Allergan, Inc., Almirall, Amgen, Inc., Arcutis, Biogen-Idec, BMS, Boehringer-Ingleheim, Breckinridge Pharma, Celgene, Centocor, Inc., Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc., Dr. Reddy’s Lab, Eli Lilly, Galderma, Genentech, Inc., GlaxoSmithKline, PLC, Idera, Johnson & Johnson, Leo, Maruho, Merck, Medicis Pharmaceutical Corp., Novartis AG, Promius, PharmDerm, Pfizer, Serono (Merck Serono International SA), Stiefel Laboratories, Inc., Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort.

Funding: This study was funded by Ortho Dermatologics.

REFERENCES

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AUTHOR CORRESPONDENCE

Leon H. Kircik MD wedoderm@yahoo.com

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