Safety of guselkumab in hepatitis B virus infection

Reactivation of hepatitis B virus (HBV) following the use of TNF antagonists has been reported and is a contraindication to use of these medications. Although the risk of reactivation of HBV during use of ustekinumab and secukinumab is low in patients with only HBV core antibody positivity, the risk is substantial in patients with chronic HBV infection. Less information is available regarding the use of pure IL-23 antagonists. Herein we discuss the successful treatment with guselkumab of a patient with HBV core antibody positivity, without evidence of HBV reactivation or other liver complications

Rapid and sustained improvements in Generalized Pustular Psoriasis Physician Global Assessment scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study

BACKGROUND: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. OBJECTIVE: To assess the effects of spesolimab over the 12-week study. METHODS: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8. RESULTS: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics. LIMITATIONS: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab. CONCLUSION: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Risk Factors and Comorbidities for Onychomycosis: Implications for Treatment with Topical Therapy

A number of comorbidities and risk factors complicate the successful management of onychomycosis. Underlying conditions and patient characteristics, such as tinea pedis, age, and obesity, contribute to risk, whereas comorbidities, such as diabetes and psoriasis, can increase susceptibility to the disease. There are limited data on treatment effectiveness in these patients. Here, the authors review post hoc analyses of efinaconazole topical solution, 10%, in mild-to-moderate onychomycosis and present new data in terms of age and obesity. The only post hoc analysis to report significant differences so far is gender, where female patients do much better; however, the reasons are unclear. The authors report significant differences in terms of efficacy in obese patients who do not respond as well as those with normal body mass index (P=0.05) and in patients who have their co-existing tinea pedis treated compared to those in whom co-existing tinea pedis was not treated (P=0.025). Although there is a trend to reduced efficacy in older patients and those with co-existing diabetes, differences were not significant. More research is needed in onychomycosis patients with these important risk factors and comorbidities to fully evaluate the treatment challengse and possible solutions

Onychomycosis: Practical Approaches to Minimize Relapse and Recurrence

INTRODUCTION: Toenail onychomycosis is a common disease in which treatment options are limited and treatment failures and disease recurrence are frequently encountered. It usually requires many months of treatment, and recurrence may occur in more than half of the patients within 1 year or more after the infection has been eradicated. Data on long-term treatment, follow-up and recurrence are limited. OBJECTIVE: Our objective is to interpret these data and recommend practical approaches that should minimize recurrence based on our clinical experience. RESULTS: Several factors have been suggested to play a role in the high incidence of recurrence, but only the extent of nail involvement and co-existing diabetes mellitus have been shown to have a significant impact. CONCLUSION: The use of topical antifungals to prevent recurrences after complete cure was achieved has been suggested by various workers and used successfully in our practice. However, it has never been validated through clinical studies. Topical prophylaxis once weekly or twice monthly would seem appropriate in those patients most at risk. Prompt treatment of tinea pedis is essential, as is ensuring family members are free from disease. Patient education and pharmacologic intervention are equally important, and there are a number of simple strategies patients can employ. Managing onychomycosis is a significant long-term commitment for any patient, and minimizing recurrence is critical to meet their expectations

Tavaborole for the treatment of onychomycosis

Onychomycosis causes approximately one-half of all nail disorders and its prevalence has been steadily increasing. It is difficult to treat, partly due to the subungual location and the inability of both oral and topical antifungals to reach the site of infection. Published cure rates with oral drugs are < 50% and even lower with topical drugs. Pathogenic factors include the diversity of fungal organisms and the difficulty of drugs penetrating the nail plate. Tavaborole is a broad-spectrum oxaborole antifungal agent with low molecular weight, permitting optimal nail plate penetration. In vitro and ex vivo studies have demonstrated the superior nail-penetrating properties of tavaborole compared to existing topical antifungal medications approved for the treatment of onychomycosis. The clinical characteristics and prevalence of onychomycosis, currently available treatments, and the chemistry, safety and pharmacokinetic properties of tavaborole for the treatment of onychomycosis. Tavaborole is a novel, topical antifungal pharmaceutical agent pending FDA approval for the treatment of toenail onychomycosis due to dermatophytes. Efficacy has been demonstrated by a clinical development program including in vitro data and two large Phase III trials that enrolled ∼ 1200 patients. When approved, tavaborole topical solution, 5% may become a safe and effective option for the treatment of onychomycosis