Publications

Engaging global key opinion leaders, the International Psoriasis Council (IPC) held a day-long roundtable discussion with the primary purpose to discuss the treatment goals of psoriasis patients and worldwide barriers to optimal care. Setting clear expectations might ultimately encourage undertreated psoriasis patients to seek care in an era in which great gains in therapeutic efficacy have been achieved. Here, we discuss the option for early treatment of all categories of psoriasis to alleviate disease impact while emphasizing the need for more focused attention for psoriasis patients with mild and moderate forms of this autoimmune disease. In addition, we encourage policy changes to keep pace with the innovative therapies and clinical science and highlight the demand for greater understanding of treatment barriers in resource-poor countries.

BACKGROUND: Long-term evaluation is required to confirm the safety profile of newer biologic agents.

OBJECTIVES: To report on pooled safety data from the ongoing VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow-up.

METHODS: Patients were randomized to either guselkumab 100 mg at weeks 0 and 4 and every 8 weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every 8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Patients who received adalimumab crossed over to guselkumab at week 52 (VOYAGE 1) and at/after week 28 based on clinical response (VOYAGE 2). Open-label extensions, in which all patients received guselkumab, started at week 52 (VOYAGE 1) and week 76 (VOYAGE 2). Rates of adverse events (AEs) per 100 patient-years (PYs) are presented through 100 weeks of follow-up.

RESULTS: Through week 52, observed rates for guselkumab- and adalimumab-treated patients, respectively, were 262·45 per 100 PYs and 328·28 per 100 PYs for AEs, 6·20 per 100 PYs and 7·77 per 100 PYs for serious AEs (SAEs), 1·22 per 100 PYs and 1·79 per 100 PYs for serious infections (SIs), 0·28 per 100 PYs and 0·40 per 100 PYs for malignancies other than nonmelanoma skin cancers (NMSCs), 0·56 per 100 PYs and 0·40 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·40 per 100 PYs for major adverse cardiovascular events (MACEs). Rates among patients treated with guselkumab through week 52 and week 100, respectively, were 262·45 per 100 PYs and 210·41 per 100 PYs for AEs, 6·20 and 6·29 per 100 PYs, for SAEs, 1·22 per 100 PYs and 1·06 per 100 PYs for SIs, 0·28 per 100 PYs and 0·38 per 100 PYs for malignancies, 0·56 per 100 PYs and 0·39 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·38 per 100 PYs for MACEs. Among patients treated with adalimumab, rates of AEs, SAEs, SIs, malignancies, NMSCs, and MACEs showed some variability before and after crossover to guselkumab, although no new safety signals were noted after crossover.

CONCLUSIONS: The safety profile for guselkumab remains favourable through 100 weeks of treatment in patients with moderate-to-severe psoriasis.

Hidradenitis suppurativa (HS) is a complex disease with a dramatic impact on the quality of life of patients that it afflicts. Despite this, there are few treatment options offering long-term relief. The exact pathophysiology of HS is unclear, although the current theory involves follicular obstruction, rupture, and subsequent inflammation leading to fistula and abscess development in intertriginous skin. Several inflammatory modulators have been implicated in the development of HS, including tumor necrosis factor (TNF)-α as well as interleukin (IL)-1β, IL-10, and IL-17. Initial evidence for the use of TNF-α inhibitors in HS stemmed from recognition that inflammatory bowel disease patients treated with these medications saw a concurrent improvement in their HS symptoms. Early case reports and case series illustrated TNF-α inhibitors' value in the treatment of HS. Later, two phase III clinical trials, PIONEER I and PIONEER II, demonstrated that adalimumab is an efficacious treatment for HS. Infliximab represents another effective HS treatment option with its main advantage being dosing flexibility. In contrast, clinical trials have failed to show evidence for application of etanercept in HS. There is limited data on other TNF-α inhibitors such as certolizumab-pegol and golimumab. This review outlines the history, dosing, response, and adverse effects of TNF-α inhibitors in the treatment of HS.

BACKGROUND: Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo-controlled trials.

OBJECTIVE: To consolidate tildrakizumab efficacy results by pooling data.

METHODS: Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled.

RESULTS: Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) 'clear' or 'minimal' vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response.

CONCLUSION: Pooled data confirmed the efficacy of tildrakizumab for moderate-to-severe plaque psoriasis.

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Aging skin is a consequence of both intrinsic factors, including genetics, and extrinsic factors, including environmental exposures such as ultraviolet (UV) radiation and smoking. This contribution focuses on intrinsic factors that promote aging skin. Specifically, in this contribution we review the literature describing how single nucleotide polymorphisms, epigenetic changes, variable gene expression, microRNA, and mitochondrial depletion relate to skin aging. Investigations studying intrinsic factors associated with skin aging are important as they promote a better understanding of the underlying pathophysiology of aging skin. This contribution also describes potential avenues for future genetic research in skin aging. Molecular mechanisms that may be therapeutically intervened upon are of particular interest given the cultural value placed on youthful appearing skin. Future research efforts will hopefully reveal a means upon which to intercede on the skin aging process.

OBJECTIVES: Hidradenitis suppurativa (HS) causes substantial morbidity and quality-of-life impairment. We examined demographic/clinical characteristics of patients with HS and treatment patterns, prevalence and healthcare resource utilisation/expenditures related to HS in the real-world.

DESIGN: Retrospective claims data of MarketScan Commercial, Medicare Supplemental and Medicaid databases (2009-2014).

SETTING: USA.

PARTICIPANTS: Patients aged ≥12 years with ≥3 non-diagnostic outpatient or inpatient claims with an HS diagnosis code and ≥12 months continuous enrolment with medical and pharmacy benefits before (preindex) and after (postindex) the earliest diagnosis of HS (index) were included.

RESULTS: There were 11 325 Commercial/Medicare patients (mean age 37.4 years) and 5164 Medicaid patients (mean age 28.3 years). HS was more common in Medicaid than Commercial/Medicare patients (0.301% and 0.098%, respectively, in 2014). Cellulitis and psychiatric disorders were the most common comorbidities and oral antibiotics and narcotics were the most frequently prescribed drugs preindex, with ≥10% increase postindex in both populations. HS-related inpatient costs decreased while outpatient costs increased from preindex to postindex. Medicaid patients had several risk factors that may be associated with poor outcomes (eg, high rates of prescription pain medication use, comorbidities, drug discontinuation/interruption/holiday, emergency department (ED) visits and hospitalisation).

CONCLUSIONS: Commercial/Medicare and Medicaid HS beneficiaries experience high comorbidity burden but use different treatment modalities to manage HS. Results suggest a substantial unmet need exists among this patient population, with Medicaid patients experiencing a particularly high burden of disease and expensive healthcare resource utilisation.