Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on quality of life, work productivity and activity impairment: a structural equation modelling analysis.

BACKGROUND: The appearance and lifelong, chronic nature of psoriasis result in considerable burden to patients, such as sleep impairment, depressive symptoms, negative self-esteem and reduced work productivity. OBJECTIVES: To examine direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity and activity impairment based on psoriasis severity and symptoms. METHODS: Analyses were based on data from the CLEAR study. Structural equation modelling examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI) severity and symptoms (pain, itching and scaling) as potential mediators. Analyses were conducted primarily for patients achieving a PASI 90 response (90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75 and 100. RESULTS: Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by the PASI 90 response and by improvements in itching, pain, and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching and scaling were correlated (r = 0·51-0·68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab. CONCLUSIONS: The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.

Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study.

BACKGROUND: Secukinumab has demonstrated significant efficacy with a good safety profile through 1 year in plaque psoriasis. Given the chronic nature of this disease, long-term follow-up is needed to evaluate psoriasis therapies fully. OBJECTIVES: To determine the long-term (3-year) efficacy and safety of secukinumab in moderate-to-severe psoriasis. METHODS: Patients completing 52 weeks of secukinumab treatment in the SCULPTURE core study entered an extension in which they continued the same double-blind regimens. Dosing regimens included a fixed-interval schedule (FI; every 4 weeks) and retreatment as needed (RAN), in which patients were withdrawn from secukinumab and received placebo until the start of relapse, at which time secukinumab every 4 weeks was reinitiated. The study was registered with number NCT01640951. RESULTS: In total 168 patients receiving secukinumab 300 mg FI and 172 receiving secukinumab 300 mg RAN entered the extension. Secukinumab 300 mg FI sustained high efficacy: at the end of year 3, the proportion of responders achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) was 63·8%, and of PASI 100 responders it was 42·6%. The mean absolute PASI remained low (2-4) from week 52 to week 152 with 300 mg FI, with approximately two-thirds of patients reporting no impact of skin disease on their lives (Dermatology Life Quality Index of 0 or 1). Improvements in overall and subscale scores on all quality-of-life instruments were well sustained. As in the core study, FI dosing was consistently more efficacious than RAN. No new safety signals were identified to year 3. CONCLUSIONS: Secukinumab 300 mg FI sustained high responses and improved quality of life with no new safety concerns through 3 years.

Secukinumab demonstrates greater sustained improvements in daily activities and personal relationships than ustekinumab in patients with moderate-to-severe plaque psoriasis: 52-week results from the CLEAR study.

BACKGROUND: Psoriasis can greatly impact patients' lives by influencing clothing worn as well as by impairing sexual functioning. Secukinumab, a human monoclonal antibody selectively neutralizing interleukin-17A, has demonstrated good efficacy and safety in the treatment of moderate-to-severe psoriasis and psoriatic arthritis with a rapid onset of action and sustained response. OBJECTIVE: This analysis using the CLEAR study, a phase 3b double-blind study comparing the efficacy and safety of secukinumab vs. ustekinumab in adults with moderate-to-severe plaque psoriasis, evaluated the treatment effects on patient's daily activities and personal relationships. METHODS: Impact on daily activities (interference with home/shopping/garden, and influence on clothes worn) and impact on personal relationships (problems with partner/others, and sexual difficulties) as well as their corresponding subscales were selected from the Dermatology Life Quality Index scale and evaluated for patients treated with secukinumab vs. ustekinumab from the CLEAR study. Treatment differences in mean scores and proportions of responders (score = 0, indicating no impact) were evaluated through 52 weeks. Time to response was evaluated through Week 16. RESULTS: Significant differences between secukinumab and ustekinumab were observed for daily activities and personal relationships at Week 16 and sustained through Week 52 (Week 52 response rates for daily activities: 82.9% vs. 73.5%, including interference with home/shopping/garden: 88.5% vs. 78.2%, and influence on clothes worn: 85.6% vs. 74.4%; personal relationships: 86.1% vs. 73.7%, including problems with partner/others: 86.6% vs. 74.8%, and sexual difficulties: 88.5% vs. 74.3%; all P < 0.01). The median time to response was 4 weeks for secukinumab vs. 8 weeks for ustekinumab for daily activities and personal relationships (both P < 0.05). CONCLUSION: Secukinumab treatment helps patients with moderate-to-severe plaque psoriasis have a more normal life faster when compared to ustekinumab, by providing greater and sustained improvement in clothing choice and sexual functioning.

Transient acantholytic dermatosis in oncology patients.

PURPOSE: To evaluate the characteristics of patients with cancer who have a previous history, concurrent episode, or subsequent appearance of transient acantholytic dermatosis (TAD). METHODS: We report four oncology patients who developed TAD and review the 22 reports that have previously been published of individuals in whom TAD appeared either before, concomitant with, or after the diagnosis of their malignancy. RESULTS: TAD was associated more frequently in patients with hematologic malignancies, especially acute and chronic myelogenous leukemia. It also appeared in patients with solid tumors, primarily those of the genitourinary organs. In almost all the cases, the onset of TAD was either concurrent or followed the discovery of malignancy. The TAD resolved completely, with or without treatment, in at least 20 patients in a median of 3 weeks. CONCLUSION: TAD is a benign and temporary condition that may occur in patients with an internal malignancy. When the diagnosis of TAD is being considered, a lesional skin biopsy readily establishes histologic confirmation in a febrile patient with cancer who develops a new rash. TAD has been observed most frequently in oncology patients who have either myelogenous leukemia or carcinoma of the genitourinary organs. The appearance of TAD coincided with either the detection or the recurrence of malignancy in three individuals (12%). In the other 23 oncology patients, TAD was most likely secondary to either antineoplastic agents, excessive perspiration, fever, occlusive immobility, and/or ionizing or UV radiation.

Treatment of a recurrent keratoacanthoma with oral isotretinoin.

BACKGROUND: Keratoacanthoma is a benign epithelial tumor that occurs on the sun-exposed skin of elderly people. Development of KAS on functionally and cosmetically important areas such as the face poses the therapeutic challenge to minimize functional and cosmetic damage. Oral isotretinoin (Accutane, Roche Laboratories) has been reported to be an effective treatment of multiple as well as solitary keratoacanthomas. CASE REPORT: A 45-year-old man with a large keratoacanthoma on the nasal ala, recurrent after surgical excision, was treated with 1 mg/kg/day (80 mg/day) oral isotretinoin (Accutane). Cessation of tumor progression was evident within 1 week after initiation of therapy, and tumor regression was evident within 2 weeks. Tumor size diminished rapidly over the ensuing weeks and complete resolution at 12 weeks was confirmed by biopsy. CONCLUSION: An initial trial of oral isotretinoin is an alternative to immediate surgical excision for the treatment of large keratoacanthomas in instances when tumor removal would cause considerable cosmetic deformity.