Efficacy and safety of apremilast and phototherapy versus phototherapy only in psoriasis vulgaris.

Phototherapy and apremilast (oral phosphodiesterase-4 inhibitor) are well-known in the treatment of moderate to severe psoriasis vulgaris. However, current evidence on the efficacy and safety of their combination is not sufficient. This multicenter, randomized controlled study compared the efficacy and safety between phototherapy as monotherapy and phototherapy and apremilast as combination therapy in patients with psoriasis vulgaris. Patients with moderate to severe psoriasis vulgaris were assigned to combination (n = 29) and monotherapy (n = 13) groups. All patients underwent an 8-week phototherapy regimen comprising irradiation with narrowband UV-B. The patients in the combination group were also administered 10 mg to 60 mg of oral apremilast. We evaluated the improvement percentage based on the Psoriasis Area and Severity Index (PASI) score from baseline to week 8. Additionally, we evaluated the percentage of patients who achieved ≥75% improvement; changes in body surface area (BSA) and scores of EuroQol 5-dimensions 5-level, Dermatology Life Quality Index, and visual analog scale for pruritis from baseline to 4 and 8 weeks; and adverse events. Compared with the monotherapy group, the combination group had significantly lower PASI scores at 4 and 8 weeks and more patients who achieved a PASI score improvement of ≥75% at 8 weeks. Both groups exhibited a significant decrease in BSA; at 8 weeks, no significant difference was observed between the two groups, although the combination group tended toward a greater reduction in BSA. The intergroup differences in the changes at the three time points were not significant. Adverse events were more frequent in the combination group than in the monotherapy group. Our findings suggest that an 8-week combined apremilast and phototherapy regimen may not be adequate in patients for improvements in their subjective assessment of psoriasis, and longer treatment periods may be necessary.

Comparison of the Efficacy and Safety of Bexarotene and Photo(Chemo)Therapy Combination Therapy and Bexarotene Monotherapy for Cutaneous T-Cell Lymphoma.

INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. The combined use of therapeutic agents and photo(chemo)therapy is widely applied for the treatment of CTCL. The efficacy and safety of bexarotene and photo(chemo)therapy combination therapy were previously confirmed in Japanese patients with CTCL. The efficacy and safety of the bexarotene and photo(chemo)therapy combination therapy was compared with bexarotene monotherapy in Japanese patients with CTCL. METHODS: This was a randomized, open-label, two-parallel-group, active-control specified clinical study in Japanese patients diagnosed with CTCL carried out over 8 weeks with a study extension conducted at two institutions. This study was registered in Japan Registry of Clinical Trials (jRCTs041180094). RESULTS: In the combination therapy group, 22 subjects received oral bexarotene (300 mg/m2 body surface area) once daily, followed by bath-psoralen and ultraviolet (UV) A or narrowband UVB. In the monotherapy group, 24 subjects received oral bexarotene (300 mg/m2) once daily. The efficacy analysis using the modified Severity-Weighted Assessment Tool, which included 39 patients, showed a response rate of 81.0% (17/21) in the combination therapy group and 83.3% (15/18) in the monotherapy group. No statistically significant difference was detected between groups. In the combination therapy group, four subjects showed a complete clinical response or complete response, and subjects with a partial response exhibited a high rate of skin lesion resolution, significantly better than in the monotherapy group. In the safety analysis, which included 46 treated subjects (22 in the combination therapy group and 24 in the monotherapy group), no adverse events or adverse drug reactions were reported in either group. CONCLUSION: Both bexarotene and photo(chemo)therapy combination therapy and bexarotene monotherapy were therapeutically effective in Japanese patients with CTCL and well tolerated. Combination therapy led to a higher skin lesion resolution rate and greater therapeutic effects compared with monotherapy. TRIAL REGISTRATION: jRCTs041180094.

This study evaluated the efficacy and safety of bexarotene monotherapy compared with bexarotene and photo(chemo)therapy combination therapy in Japanese patients with cutaneous T-cell lymphoma (CTCL). The study was a randomized, open-label, two-parallel-group, active-control specified clinical study in patients diagnosed with CTCL performed over an 8-week period with a study extension conducted in two institutions. In the combination therapy group, bexarotene (300 mg/m² body surface area) was administered orally once daily to 22 subjects, followed by treatment with bath-psoralen and ultraviolet A (bath-PUVA) or narrowband UVB. In the bexarotene monotherapy group, bexarotene (300 mg/m²) was administered orally once daily to 24 subjects. Efficacy was assessed using the modified Severity-Weighted Assessment Tool. Among the 39 subjects analyzed for treatment efficacy, the response rate of the combination therapy group was 81.0% (17/21) and that of the monotherapy group was 83.3% (15/18). Differences between the two treatment groups were not statistically significant. Of the 21 subjects in the combination therapy group, 4 had a complete clinical response or complete response, and those with a partial response showed a higher skin lesion resolution rate than in the monotherapy group. The safety analysis revealed no reports of adverse events or adverse drug reactions among the 46 treated subjects (combination therapy group = 22; monotherapy group = 24). Thus, both bexarotene and photo(chemo)therapy combination therapy and bexarotene monotherapy were therapeutically effective and well tolerated in Japanese patients with CTCL. Patients receiving the combined therapy, however, showed a higher rate of skin lesion resolution.

A multicenter, open-label, uncontrolled, single-arm phase 2 study of tirabrutinib, an oral Bruton's tyrosine kinase inhibitor, in pemphigus.

BACKGROUND: The treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling. OBJECTIVE: We investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus. METHODS: This was a multicenter, open-label, single-arm phase 2 study of Japanese patients with refractory pemphigus receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent. RESULTS: In total, 16 patients were evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 6.6 %-43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A relationship with tirabrutinib was ruled out for all serious AEs and Grade ≥3 AEs. CONCLUSION: Treatment with tirabrutinib enabled remission and reduced oral corticosteroid exposure over time and did not result in any major safety concerns in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new treatment option for patients with refractory pemphigus.

Efficacy and safety of bexarotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. International treatment guidelines for CTCL are widely followed in Europe and the USA. Combination therapy with therapeutic agents for CTCL and phototherapy is effective on the basis of European data. The efficacy and safety of combination therapy for Japanese CTCL patients are not established. We investigated the efficacy and safety of combination therapy with photo(chemo)therapy and bexarotene in Japanese CTCL patients. Twenty-five patients received daily oral bexarotene (300 mg/m2 body surface), followed by bath-psoralen plus ultraviolet (UV)-A (PUVA) or narrowband UV-B. Treatment results were evaluated using the modified Severity-Weighted Assessment Tool (mSWAT) and the Physician Global Assessment of Clinical Condition (PGA) up to week 24. Safety was also assessed. Twenty-four weeks after initiating treatment, the total response rate was 80.0% (mSWAT) and 84.0% (PGA). Response rates did not differ when stratified by disease stage. Number of days (mean ± standard deviation) for time to response, duration of response and time to progression determined by the mSWAT were 20.7 ± 9.62, 117.0 ± 43.0 and 163.6 ± 28.8, respectively. T-helper 2 chemokine levels in patients at stage IIA or more decreased significantly at weeks 12 and 24. All patients experienced adverse events and adverse drug reactions. Serious adverse drug reactions included sepsis, anemia and congestive cardiac insufficiency (n = 1 each). Other adverse drug reactions were of mild to moderate severity. Combination therapy with bexarotene and PUVA was safe and effective in Japanese CTCL patients.

Intense pulsed light therapy for aberrant Mongolian spots.

BACKGROUND: Aberrant Mongolian spots (AMS) distal to the lumbosacral region are thought to be more likely to persist than typical sacral Mongolian spots. So far, Q-switched ruby laser (QSRL) has been the treatment of choice for AMS. Intense pulsed light (IPL) is obtained from flashlamp devices that emit wavelengths between 515 and 1200 nm. IPL has documented efficacy for the treatment of irregular pigmentation, telangiectasia, rough skin texture, rhytids, hair removal, and vascular lesions, with several filters being available that can be used to block shorter wavelengths from the skin. As far as we could determine, there have been no clinical and histological studies on the treatment of AMS with IPL. Accordingly, the aim of this study was to assess the clinical and histological efficacy of IPL for AMS. METHODS: Seven patients (4 males and 3 females) presenting from September 2008 to July 2009 were assessed. Their mean age was 2.0 years, ranging from 0 to 7 years. The IPL device used in this study was a Natulight (Lumenis Ltd., Tokyo, Japan). Photographs were taken of all patients with a high-resolution digital camera at baseline and 6 months after treatment. Skin biopsy specimens were taken from 1 patient (case 4) before, immediately after, and 6 months after treatment. RESULTS: According to the 7 family members of the patients, the outcome of IPL was graded as follows: excellent improvement in 1 (14%), good improvement in 4 (57%), and slight improvement in 2 (29%). All families would have liked to continue IPL treatment. Evaluation of the effect of treatment by a physician was less favorable, with excellent improvement in 1 (14%), good improvement in 2 (29%), and slight improvement in 4 (57%). Histopathologic examination of the pigmented region revealed the typical features of a Mongolian spot in the hematoxylin-eosin stained section. Immediately after IPL, there were no changes in the dermis. At 6 months after treatment, however, the number of melanocytes in the middle and upper dermis was obviously decreased. CONCLUSIONS: IPL is an effective method for the treatment of AMS.