Ixekizumab and Ustekinumab Efficacy in Nail Psoriasis in Patients with Moderate-to-Severe Psoriasis: 52-Week Results from a Phase 3, Head-to-Head Study (IXORA-S).

INTRODUCTION: Patients with plaque psoriasis often have nail psoriasis, which is difficult to treat. Ixekizumab (IXE) and ustekinumab (UST) are biologics with established efficacy in nail psoriasis. We present post hoc data from a head-to-head trial of IXE and UST (IXORA-S) to examine the efficacy in nail psoriasis in patients with moderate-to-severe plaque psoriasis over 52 weeks. METHODS: In IXORA-S, randomised patients received IXE (N = 136) or UST (N = 166) per label for 52 weeks. Eighty-four (61.8%) and 105 (63.3%) of the patients treated with IXE or UST, respectively, had baseline fingernail psoriasis (Nail Psoriasis Severity Index [NAPSI] > 0); of these, 54 (64.3%) and 63 (60.0%) patients, respectively, had significant baseline fingernail psoriasis (defined as NAPSI ≥ 16 with ≥ 4 fingernails involved). The proportion of patients achieving NAPSI = 0, a NAPSI score change from baseline and correlations in Psoriasis Area of Severity Index (PASI) and NAPSI improvement over 52 weeks were examined. RESULTS: Progressive improvement occurred in both treatment groups over 52 weeks. Statistically significantly more patients achieved NAPSI = 0 with IXE versus UST by week 16-20, and the proportions continued to increase through week 52 among patients with baseline nail psoriasis (61.9 vs. 28.6%, respectively; P < 0.001), including those with significant nail psoriasis (57.4 vs. 17.5%, respectively; P < 0.001). Similar results were observed for NAPSI score improvement from baseline to week 52. Interestingly, the presence of nail psoriasis was associated with lower skin response with UST but not with IXE. CONCLUSIONS: Ixekizumab was superior to UST in the clearance of nail psoriasis, with earlier improvement continued through 52 weeks regardless of baseline nail severity. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02561806.

Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis.

BACKGROUND: Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. OBJECTIVE: We evaluated the efficacy and safety of apremilast in palmoplantar psoriasis. METHODS: A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1). RESULTS: Significantly more patients taking apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group (P < .001); 59% of the apremilast group had a PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving placebo (P < .001). LIMITATIONS: This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. CONCLUSION: Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.

Secukinumab in plaque psoriasis--results of two phase 3 trials.

BACKGROUND: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). RESULTS: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).

Immune response to pneumococcus and tetanus toxoid in patients with moderate-to-severe psoriasis following long-term ustekinumab use.

BACKGROUND: Little is known about the impact of long-term use of immunosuppressive agents on immune response. OBJECTIVES: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines. PATIENTS AND METHODS: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination and 4 weeks post-vaccination were assessed for antibody responses. RESULTS: No differences in the ability of ustekinumab-treated patients to respond to pneumococcal or tetanus toxoid vaccinations were observed compared with controls. A ≥2-fold increase in antibody levels in ≥7 of 14 serotypes of the pneumococcal vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%) patients following vaccination. Ustekinumab-treated patients achieved a ≥4-fold increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid between ustekinumab-treated and control groups. CONCLUSION: Long-term treatment (≥3 years) with ustekinumab does not compromise the immune response to T-cell-dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

Evaluating practice patterns for managing moderate to severe plaque psoriasis: role of the family physician.

OBJECTIVE: To describe practice patterns for care of Canadian patients with moderate to severe plaque psoriasis. DESIGN: Online survey of a consumer panel. SETTING: Participants were drawn from a population-wide Canadian consumer database. PARTICIPANTS: To be eligible to participate, respondents had to have been diagnosed with plaque psoriasis within the past 5 years, and to have had body surface area involvement of 3% or greater in the past 5 years, or to have psoriasis on a sensitive area of the body (hands, feet, scalp, face, or genitals), or to be currently receiving treatment with systemic agents or phototherapy for psoriasis. MAIN OUTCOME MEASURES: Proportion of respondents with psoriasis managed by FPs and other specialists, psoriasis therapies, comorbidities, and patient satisfaction. RESULTS: Invitations were sent to 3845 panelists with self-reported psoriasis, of which 514 qualified to complete the survey. Family physicians were reported to be the primary providers for diagnosis and ongoing care of psoriasis in all provinces except Quebec. Overall physician care was reported to be satisfactory by 62% of respondents. Most respondents receiving over-the-counter therapies (55%) or prescribed topical therapies (61%) reported that their psoriasis was managed by FPs. Respondents receiving prescription oral or injectable medications or phototherapy were mainly managed by dermatologists (42%, 74%, and 71% of respondents, respectively). Ongoing management of respondents with body surface area involvement of 10% or greater was mainly split between dermatologists (47%) and FPs (45%), compared with rheumatologists (4%) or other health care professionals (4%). Of those respondents receiving medications for concomitant health conditions, treatment for high blood pressure was most common (92%), followed by treatment for heart disease (75%) and elevated cholesterol and lipid levels (68%). CONCLUSION: Patient-reported practice patterns for the diagnosis and management of moderate to severe psoriasis vary among provinces and in primary and secondary care settings.

Topical psoriasis therapy in the age of biologics: evidence-based treatment recommendations.

BACKGROUND: Although the range of therapeutic options has expanded dramatically in recent years, topical agents remain ubiquitous and indispensable tools for treating psoriasis at all levels of severity. The 2009 Canadian psoriasis guidelines considered evidence supporting various monotherapies and combination regimens. OBJECTIVE: Here we review all approved topical agents, including corticosteroids, calcineurin inhibitors, vitamin D analogues, and retinoids, used in psoriasis and develop additional treatment recommendations, using the Scottish Intercollegiate Guidelines Network (SIGN) system to evaluate strength of evidence, as in the original guidelines. CONCLUSION: We propose that topical treatments have a place in the long-term management of patients with moderate to severe plaque psoriasis, including those receiving concomitant photo- or systemic therapy. Topical agents are effective and appropriate treatments for psoriasis as long as the physician is attentive to signs of local adverse events and seeks opportunities to reduce the dose or treatment frequency during chronic use.

Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To determine the efficacy, safety, and sustainability of response to adalimumab therapy for moderate to severe chronic plaque psoriasis involving hands and/or feet. DESIGN: Sixteen-week, randomized, double-blind, placebo-controlled evaluation of adalimumab therapy for moderate to severe chronic plaque psoriasis involving the hands and/or feet with a 12-week open-label extension (Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet [REACH]). SETTING: Multicenter outpatient study in the United States and Canada. PARTICIPANTS: Patients with chronic plaque psoriasis on the hands and/or feet with a Physician's Global Assessment of hands and/or feet (hfPGA) score of "moderate" or above. INTERVENTION: Patients were randomized 2:1 to adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) or to matching placebo. MAIN OUTCOME MEASURE: Percentage of patients achieving an hfPGA score of "clear" or "almost clear" at week 16. RESULTS: Seventy-two patients (adalimumab [n = 49];placebo [n = 23]) were evaluated. Baseline percentages of patients with moderate and severe hfPGA scores were 76% and 24%, respectively, for the adalimumab group and 74% and 26%, respectively, for the placebo group. At week 16, 31% and 4% of patients randomized to adalimumab and placebo, respectively, achieved an hfPGA score of clear or almost clear (P = .01). At week 28, 80% of the hfPGA clear or almost clear response was maintained from week 16 (25% for patients randomized to adalimumab). Adverse events in both groups were generally mild to moderate. In both periods combined, nasopharyngitis (27% and 13% for adalimumab- and placebo-treated patients, respectively) was most frequently reported. CONCLUSION: Adalimumab is efficacious and well tolerated for treatment of chronic plaque psoriasis of hands and/or feet, with efficacy largely maintained to 28 weeks. Trial Registration clinicaltrials.gov Identifier: NCT00735787.

A Canadian online survey to evaluate awareness and treatment satisfaction in individuals with moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with comorbidities and decreased quality of life. This survey is aimed to better understand the impact of disease on Canadian patients, and to examine awareness and use of available treatment options. METHODS: An online survey was conducted using a consumer panel. Eligible subjects reported diagnoses of psoriasis and moderate/severe/very severe plaque psoriasis within the past 5 years, and either: psoriasis covering ≥ 3% of body surface area; psoriasis on a sensitive area, or current use of systemic and/or phototherapy or light therapy for psoriasis. RESULTS: A total of 514 panelists completed the survey; 65% reported current moderate/severe/very severe psoriasis. Awareness of available treatment options ranged from 98% for prescription topical agents to 75% for photo/light therapy, and < 50% for prescription oral (49%) or injectable (35%) medications. A total of 92% of respondents had been treated with and 61% were currently taking prescription topical agents. Photo/light therapy had been used by 38% and was currently used by 7% of respondents. Prescribed oral medication had been taken by 25% and was currently used by 8%. Few subjects had been treated with injectables in the past (10%) or currently (5%). Overall, 24% of respondents were very satisfied with their current treatment. A total of 63% of respondents taking injectables were very satisfied, compared with 38% of those taking prescribed oral medication and 21% of those receiving photo/light therapy.Conclusions Most respondents with moderate to severe psoriasis were unaware of all treatment options; systemic treatments were not commonly utilized. Treatment satisfaction rates were low, highlighting the need to ensure greater patient education on and use of available therapeutic options.

Epidemiology of moderate-to-severe plaque psoriasis in a Canadian surveyed population.

BACKGROUND: limited data are available on the epidemiologic features of psoriasis in Canada. OBJECTIVE: to investigate the epidemiologic features and burden of moderate-to-severe psoriasis in a Canadian population. METHODS: an online survey was conducted using a consumer panel. Eligible respondents indicated a diagnosis of psoriasis and plaque-type psoriasis of at least moderate severity. Eligibility was validated according to self-reported body surface area (BSA) involvement, sensitive areas affected, and/or current treatment. RESULTS: of the 514 respondents who completed the survey, 62% estimated a BSA involvement of >/= 3% within the past 5 years. Onset of psoriasis occurred earlier in females than in males. Nail involvement was more commonly reported in individuals with psoriatic arthritis compared to those without. Several symptoms were more likely described as "constantly" or "near constantly" experienced by females than by males. Comorbidities commonly reported were hypertension, dyslipidemia, and overweight or obesity. CONCLUSIONS: the findings are consistent with a substantial burden attributed to moderate-to-severe plaque psoriasis in a Canadian population.

A Canadian self-administered online survey to evaluate the impact of moderate-to-severe psoriasis among patients.

BACKGROUND: Few population studies of individuals living with psoriasis have been performed in Canada. OBJECTIVE: The objective of this survey was to understand the severity and impact of psoriasis on the lives of Canadian patients. METHODS: An online survey was conducted using a consumer panel. Eligible subjects reported a diagnosis of psoriasis and provided a self-reported level of severity. In addition, subjects had to either (a) have psoriasis covering at least 3% of their body surface area; (b) have psoriasis on a sensitive area of the body; or (c) be currently undergoing treatment for their psoriasis with systemic medication and/or phototherapy. RESULTS: A total of 514 panelists met the inclusion criteria and completed the survey. Current moderate, severe, or very severe psoriasis was reported by 65% of respondents. Nearly all subjects (96%) had psoriasis affecting a sensitive area of the body. At the time of the survey, 18% were taking systemic medication and/or phototherapy. Comorbidities, such as obesity and high blood pressure, were highly prevalent, with 75% of respondents reporting at least one other diagnosis. Data from the SF-8 and Dermatology Life Quality Index instruments indicated that psoriasis negatively impacted quality of life. CONCLUSION: Moderate-to-severe psoriasis places a burden on Canadian patients, some of whom may be receiving suboptimal treatment or treatment not appropriate for the severity of their condition.

Lupus vulgaris occurring in a locus minoris resistentiae.

BACKGROUND: The pathogenesis of lupus vulgaris, a form of cutaneous tuberculosis, is not always clear, especially in patients who do not have coexistent extracutaneous tuberculosis and in patients with single lesions. OBJECTIVES: To report a case of lupus vulgaris in a locus minoris resistentiae (a site of reduced resistance) and to use a unique set of clinical circumstances and laboratory tests to reconstruct the pathogenesis of the lesion and the response to treatment. CONCLUSION: Lupus vulgaris can occur in a locus minoris resistentiae; local trauma and possibly other factors, such as increased temperature, topical corticosteroids, and the virulence of the infecting strain, may facilitate the growth of Mycobacterium tuberculosis present at a locus minoris resistentiae as a result of a silent bacillemia.

Successful hair transplant of eyebrow alopecia areata.

BACKGROUND: Alopecia areata of the eyebrows can be difficult to treat. Intralesional triamcinolone or potent topical steroids are considered the mainstay of medical therapy. This case illustrates the results of an experimental hair transplant to the eyebrows following years of modest response to intralesional triamcinolone. OBJECTIVE: The aim of this study was to ascertain the benefits of a hair transplant for chronic eyebrow alopecia areata not responding to appropriate medical therapy. METHODS: A hair transplant was performed with tumescent anesthesia and a total of 85 mini and micrografts placed in the right eyebrow. Followup after the hair transplant occurs every 8 weeks. RESULTS: The patient was free of eyebrow alopecia areata for 8 months following the initial hair transplant. Although the disease relapsed, hair growth is now manageable with intralesional cortisone injection performed six times per year. CONCLUSIONS: For the first time in years, this patient was given 8 months of reprieve from his eyebrow alopecia areata and is currently well-maintained on monthly intralesional cortisone which originally was of only modest benefit. The patient is pleased with the outcome.