Efficacy and Safety of Toreforant, a Selective Histamine H4 Receptor Antagonist, for the Treatment of Moderate-to-Severe Plaque Psoriasis: Results from a Phase 2 Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Toreforant is a selective histamine H4 receptor antagonist. H4 receptor activation may play a role in immune-mediated inflammation in psoriasis. OBJECTIVE: To evaluate Toreforant efficacy and safety in patients with moderate-to-severe psoriasis. METHODS: Biologic-naïve patients were to be treated (30, 60, or 3 mg Toreforant or placebo) for 12 weeks and followed through week 16. In this adaptive-design study, assignments were guided by interim analyses. Primary and major secondary efficacy endpoints, evaluated using Bayesian analyses, were the proportions of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline and achieving Investigator's Global Assessment (IGA) of cleared (0) or minimal (1), respectively, at week 12. RESULTS: Per interim analyses results, patients were randomized to 30 (n = 30) or 60 mg (n = 26) Toreforant or placebo (n = 6). The estimated mean difference in the PASI 75 response rate at week 12 from the posterior distributions compared to placebo was 14.1% (95% credible interval [CI], -0.1% to 30.9%) and 8.9% (95% CI, -5.0% to 24.3%) with 30 and 60 mg Toreforant, respectively. The posterior probabilities of 30 and 60 mg Toreforant inducing a greater response rate than placebo were 97.4% and 90.3%, respectively; neither met the 97.5% predefined success criterion. Results for the IGA 0/1 endpoint were similar. Toreforant was generally safe and well tolerated. No deaths, serious or opportunistic infections, active tuberculosis, or malignancies were reported. CONCLUSIONS: Toreforant efficacy at 30 and 60 mg was greater than placebo but did not meet predefined success criterion. J Drugs Dermatol. 2018;17(8):873-879.

Efficacy of Secukinumab in the Treatment of Moderate to Severe Plaque Psoriasis in the North American Subgroup of Patients: Pooled Analysis of Four Phase 3 Studies.

INTRODUCTION: Demographic and disease characteristics may impact response to psoriasis therapies. The objective of this study is to explore the safety and efficacy profile of secukinumab in North American (NA) versus non-NA patients with moderate to severe psoriasis. METHODS: Data were pooled from four phase 3 studies of secukinumab. Secukinumab (300 and 150 mg) was administered at baseline, weeks 1, 2, and 3, then every 4 weeks from week 4 to 48. RESULTS: Peak efficacy was observed at week 16 in NA and non-NA patients with secukinumab 300 mg and secukinumab 150 mg, and disease clearance was maintained to week 52. At week 52 with secukinumab 300 mg, Psoriasis Area and Severity Index (PASI) 90/100 response was achieved by 62.9%/37.9% of NA patients, respectively, and 70.2%/42.0% of non-NA patients, respectively. At week 52 with secukinumab 150 mg, PASI 90/100 response was achieved by 30.9%/17.5% of NA patients, respectively, and 53.9%/26.9% of non-NA patients, respectively. Response to secukinumab was rapid, and 50% reduction in mean PASI was achieved in both groups after 2.9 weeks with secukinumab 300 mg and 3.7 weeks with secukinumab 150 mg. CONCLUSION: Despite differences in baseline characteristics, the efficacy and safety of secukinumab were similar among NA and non-NA patients. FUNDING: Novartis Pharma AG. Plain language summary available for this article.

Efficacy and Safety of Once-Daily Dapsone Gel, 7.5% for Treatment of Adolescents and Adults With Acne Vulgaris: Second of Two Identically Designed, Large, Multicenter, Randomized, Vehicle-Controlled Trials.

BACKGROUND: Dapsone gel, 5% is administered twice daily for the treatment of acne vulgaris, and some patients may find adherence challenging.
OBJECTIVE: The study objective was to assess the efficacy and safety, compared with vehicle, of acne treatment with a recently FDA-approved, once-daily formulation of dapsone gel, 7.5%, with a 50% greater concentration of dapsone.
METHODS: This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients aged 12 years and older with 20-50 facial inflammatory lesions, 30-100 facial noninflammatory lesions, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized (1:1 ratio) to topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with a GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
RESULTS: The intent-to-treat population comprised 2238 patients (1118 in the dapsone gel, 7.5% group and 1120 in the vehicle group). The GAAS success rates were 29.8% for the dapsone gel, 7.5% group and 20.9% for the vehicle group (P<0.001) at week 12. At week 12, mean inflammatory lesions decreased from baseline by 53.8% and 47.3%, noninflammatory lesions decreased by 45.9% and 40.4%, and total lesions decreased by 48.9% and 43.2% for the dapsone gel, 7.5% group and the vehicle group, respectively (all, P<0.001). The incidence of treatment-emergent adverse events was similar for dapsone gel, 7.5% (17.6%) and vehicle (17.1%). Most adverse events were mild to moderate in severity. The most frequently reported increase in severity for all of the dermal tolerability scales was from "none" to "mild."
CONCLUSION: Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne vulgaris. Improvements in acne severity and lesions were observed over the 12-week course of treatment.

J Drugs Dermatol. 2016;15(8):962-969.

The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis.

BACKGROUND: Safety and efficacy of up to 3 courses of alefacept intramuscular (IM) in the treatment of chronic plaque psoriasis have been demonstrated in earlier trials. OBJECTIVE: We sought to determine the safety and efficacy of up to 5 courses of alefacept IM in treating plaque psoriasis. METHODS: A standard treatment course was defined as 15 mg of alefacept IM once weekly for 12 weeks, followed by 12 weeks of treatment-free observation. Patients with chronic plaque psoriasis, who had previously received alefacept IM, received up to 3 additional courses (A, B, and C). Efficacy was evaluated by Physician Global Assessment. RESULTS: Safety profiles were similar to those for a single course of treatment. There were no cumulative adverse effects. At 2 weeks postdosing, 16%, 22%, and 19% of patients were rated clear or almost clear by Physician Global Assessment in courses A, B, and C, respectively, with 35%, 42%, and 42% achieving this response at any time during these courses. Patients who achieved clear or almost clear at 2 weeks postdosing remained so for a median duration of 214 and 126 days after courses A and B, respectively. LIMITATIONS: This was an extension study and therefore contained no control group. CONCLUSIONS: Up to 5 courses of alefacept IM may provide extended treatment-free, symptom-free periods in responders while maintaining the safety profile.

Reduction in Procedure-associated Pain by Treatment with a Unique Topical Anesthetic Foam Containing 4% Lidocaine.

OBJECTIVE: This study evaluated a unique formulation of lidocaine 4% in an emollient aerosol foam microemulsion system to facilitate rapid delivery of the active ingredient and reduce pain associated with cosmetic dermatologic laser treatment. DESIGN: This was a noncontrolled, open-label, paired, comparison study. SETTING: Private practice dermatology clinic. PARTICIPANTS: Ten patients undergoing various cosmetic laser treatments, 18 years of age or older and considered clinically appropriate for study participation. MEASUREMENTS: Primary endpoints were patient and clinician assessments of procedural pain intensity for the treated and untreated areas. Ratings were recorded on a visual analog scale ranging from "no pain at all" to "the most intense pain imaginable." Secondary study endpoints included clinician and patient subjective assessments of the lidocaine 4% foam. RESULTS: Mean patient and clinician ratings of pain were significantly lower for areas treated with the lidocaine 4% foam compared with pain ratings for untreated areas. No adverse events were reported. Clinician's mean ratings for ease of application and overall satisfaction were favorable. CONCLUSION: The results from this pilot, 10-patient, open-label study suggest that the lidocaine 4% foam may be acceptable to both patients and clinicians for the safe and effective reduction of pain associated with cosmetic dermatologic laser procedures. However, a blinded, placebo-controlled study of a larger population is needed to confirm these preliminary results.

Etanercept improves psoriatic arthritis patient-reported outcomes: results from EDUCATE.

Experience Diagnosing, Understanding Care, and Treatment With Etanercept (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in routine dermatologic practice. We present data on patient-reported outcomes (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically meaningful improvements in both skin- and joint-related PROs after 24 weeks of treatment.

Efficacy of etanercept in an integrated multistudy database of patients with psoriasis.

BACKGROUND: The tumor necrosis factor (TNF) inhibitor etanercept has been demonstrated to be safe and effective for treating chronic plaque psoriasis in 3 clinical trials. OBJECTIVES: To refine efficacy results for etanercept on the basis of a larger population size through the integration of the 3 studies, and to determine if the efficacy profile across all 3 studies is consistent with efficacy profiles observed for individual trials. METHODS: In these integrated analyses, data for 1187 patients from 3 blinded treatment groups were pooled to compare efficacy at 12 weeks: etanercept 50 mg weekly (equivalent to 25 mg twice weekly) subcutaneously, etanercept 50 mg twice weekly subcutaneously, and placebo. The primary efficacy end point in all 3 studies was at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75). Other measurements included PASI 50, PASI 90, patient's and dermatologist's global assessments, and Dermatology Life Quality Index. RESULTS: In the integrated analyses, statistically significant, dose-dependent improvements in PASI 75 at 12 weeks were observed in patients treated with etanercept 50 mg weekly (33%) and 50 mg twice weekly (49%), compared with the placebo group (3%; P < .05). Significant improvements also were seen in all secondary end points (PASI 50 and PASI 90 responses, patient's and dermatologist's global assessments, and Dermatology Life Quality Index) at 12 weeks. Subgroup analyses of baseline patient characteristics demonstrated that there were no statistically significant treatment-by-covariate interactions. LIMITATIONS: A limitation of these integrated analyses is the relatively short (12-week) time frame. CONCLUSION: The efficacy profile of etanercept in patients with psoriasis was consistent across multiple studies as shown in the integrated analyses of the primary and secondary end points. Etanercept demonstrated rapid, dose-dependent improvements in disease severity and quality of life consistently over all studies.

Use of etanercept for psoriatic arthritis in the dermatology clinic: the Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study.

OBJECTIVE: To assess the efficacy and tolerability of etanercept to treat psoriatic arthritis. MATERIALS AND METHODS: A total of 1,122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. These patients had clinically stable, plaque psoriasis involving >or=10% body surface area and joint disease (either >or=two swollen and >or=two tender/painful joints for >or=3 months, or >or=one joint with sacroiliitis or spondylitis). They received etanercept therapy 50 mg subcutaneously once weekly for 24 weeks. RESULTS: After 24 weeks of treatment, 865 patients (77.1%; 95% CI: 74.64-79.55%) achieved a 'mild or better' score on the physician global assessment of psoriasis and were improved from baseline. Mean improvement in body surface area involvement was 16.9 percentage points (15.89-17.91). Patient global assessment of psoriasis, joint pain, and joint disease scores were improved by means of 2.2 (2.15-2.34), 2.7 (2.53-2.84), and 1.5 (1.39-1.55), respectively. Thirty-five patients (3.1%) experienced at least one serious adverse event. No patient died during the study. CONCLUSIONS: These results support the effectiveness and tolerability of etanercept treatment in patients with psoriatic arthritis being treated at dermatology clinics.

CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study.

BACKGROUND: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis. OBJECTIVE: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed. METHODS: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10. RESULTS: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%). CONCLUSION: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.