Daniel J. No

Drug survival of biologic treatments in psoriasis: a systematic review

Abstract Drug survival measures the length of time until discontinuation of a drug. The length of time a patient remains on a biologic drug is impacted by several factors such as tolerability, side effects, safety profile and effectiveness. To evaluate the long-term drug survival, data of the most commonly prescribed biologic medications used in the treatment of psoriasis, a systematic review was conducted. A literature search using PubMed, the Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature from January 1 2010 to October 28 2016 identified 3734 abstracts. Of which, 36 publications with over 40,000 patients met the inclusion criteria. The median overall drug survival for ustekinumab, adalimumab, infliximab and etanercept was 38.0, 36.5, 26.6 and 24.7 months, respectively. The mean annual drug survival rate of TNF inhibitors was 70%, 57%, 51%, 45% and 41% at years-1, 2, 3, 4 and 5, respectively. The 5-year mean annual drug survival rate of ustekinumab was 87%, 78%, 70%, 71% and 51%, respectively. Based on our findings, ustekinumab appears to have a longer drug survival with lower rates of discontinuation compared to tumor necrosis factor inhibitors.

Review of IL-17 inhibitors for psoriasis

Abstract Background: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. Objective: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. Methods: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Results: At week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was above 60% for the most efficacious dose of each agent with favorable and comparable safety profiles. The most commonly reported adverse events were nasopharyngitis, headache, and upper respiratory tract infection. Conclusions: The clinical improvement among psoriasis patients on IL-17 inhibitors is similar or superior to the improvement seen with commercially produced biologic agents available accompanied by a favorable short-term safety profile. The results of the phase III trials indicate that IL-17 inhibitors are effective therapeutic options for psoriasis patients.

Choosing First-Line Biologic Treatment for Moderate-to-Severe Psoriasis: What Does the Evidence Say?

An advanced understanding of the pathogenesis of psoriasis has led to the development of multiple therapeutic options for moderate-to-severe psoriasis. Tumor necrosis factor inhibitors, ustekinumab, interleukin-17 inhibitors, and guselkumab (an interleukin-23 inhibitor recently approved for psoriasis) are commercially available biologic agents for psoriasis. Evidence from clinical trials provides pertinent information regarding the safety and efficacy of biologic agents for psoriasis, which should be integrated into clinical decision making. However, disease presentations, disease severity, and comorbid conditions can complicate the choice of initial treatment, which underscores the importance of providing personalized therapy for patients with psoriasis. Furthermore, each biologic agent offers unique benefits and limitations for the treatment of patients with psoriasis. Here, evidence-based recommendations are presented and discussed regarding first-line biologic therapy options for patients with psoriasis and distinct comorbid conditions or patient-related factors. We discuss the comorbid conditions of psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, and latent tuberculosis. Moreover, we describe treatment recommendations for distinct patient populations with psoriasis, including pediatric patients with psoriasis and patients with psoriasis of childbearing potential and nursing.

Interpreting Clinical Trial Data

Effective interpretation of clinical trial data allows for the integration of high-quality clinical research into clinical practice. Evidence from clinical trials directly impacts clinical decision making, which ultimately guides patient management (Page, Int J Sports Phys Ther 9: 726, 2014). The purpose of this chapter is to provide an overview of fundamental aspects of clinical trials, such as study designs, analyses, and methods of handling missing data along with potential sources of bias and uncertainty. Subject withdrawal can make statistical analysis difficult as studies are aimed to determine the impact of an intervention from beginning to end. The different approaches to account for missing data are presented: last observation carried forward (LOCF), nonresponder imputation (NRI), as-observed data analysis, and anytime analysis (Langley and Reich, Br J Dermatol 169:1198–1206, 2013). Identifying sources of error and understanding limitations of these methods helps clinicians evaluate the validity of clinical data, ultimately enhancing clinical decision making and patient care.

Risk of aortic aneurysm in patients with psoriasis: a retrospective cohort study

e N, Street J et al. Effective management of advanced angiosarcoma by the synergistic combination of propranolol and vinblastine-based metronomic chemotherapy: a bench to bedside study. EBioMedicine 2016; 6: 87–95. 6 Daguz e J, Saint-Jean M, Peuvrel L et al. Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. JAAD Case Rep 2016; 2: 497–499. 7 Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, Bryan BA. Growth attenuation of cutaneous angiosarcoma with propranololmediated b-blockade. JAMA Dermatol 2015; 151: 1226–1229. 8 Pasquier E, Ciccolini J, Carre M et al. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget 2011; 2: 797– 809. 9 Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience 2015; 9: 499. 10 Dose-Finding of Propranolol in Combination With Metronomic Fixed Oral Cyclophosphamide Based on Bivariate Efficacy-tolerability Outcome in Patients With Locally Advanced or Metastatic Angiosarcoma: a Collaborative and Innovative Phase I-II Sequential Trial by the French Sarcoma Group (GSF/GETO) – Full Text View – ClinicalTrials.gov. URL https://clinicaltrials.gov/ct2/show/NCT02732678 (last accessed: 11 May 2017).

A systematic review of active comparator controlled clinical trials in patients with moderate-to-severe psoriasis

Abstract Purpose: Interleukin (IL)-17 and IL-23 inhibitors are the newest biologic agents used in the management of moderate-to-severe psoriasis. Active comparator studies allow for direct comparison of different biologic agents. We sought to systematically investigate the efficacy of newer biologic agents compared to earlier biologics. Materials and methods: We conducted a literature search for randomized control trials that compared the efficacy of a biologic agent with an active comparator. Articles from January 1 2010 to June 26 2017 were searched. Reference lists were also reviewed for studies for inclusion. Results: Twelve studies were included, a majority being phase III trials. All of the studies compared the efficacy of IL-17 and IL-23 inhibitors with adalimumab, etanercept, or ustekinumab with the exception of one study that compared the efficacy of ustekinumab with etanercept. IL-17 and IL-23 inhibitors consistently demonstrate superior efficacy over TNF inhibitors and ustekinumab as assessed by 75%, 90%, and 100% improvement in baseline Psoriasis Area and Severity Index (PASI) scores at week 12. Conclusions: Overall, IL-17 and IL-23 inhibitors appear to demonstrate superior efficacy and more rapid clinical improvement when compared to older biologic agents. This review may help predict patient outcomes, manage patient expectations, and biologic agent utilization.

Atopic dermatitis 2017: where we were 10–15 years ago in psoriasis

Abstract Novel and innovative treatment options for atopic dermatitis (AD) are underway. The recent advancements in understanding AD are reminiscent of the progress made in psoriasis research over a decade ago.

Severely Obese 42-Year-Old with Psoriasis

Psoriasis is associated with a range of diseases, including obesity. Debate exists regarding which of these two conditions comes first. In patients who weigh more, first-line biological drug choices include infliximab and ustekinumab because they are weight based. On the other hand, systemic treatments can often cause adverse effects and metabolic derangements in these patients.

70-Year-Old Male with Red Rash on Palms

A 70-year-old man presented with a 5-year history of persistent, pruritic, non-tender, erythematous thick plaques on both hands and feet. He denied any prior bleeding or ulceration at the site of the rash. He had previously used topical antifungal creams that were discontinued after they proved to be ineffective. The patient is retired and denied excessive exposure to water or contact with irritants such as detergents, solvents, and adhesives. The patient also complained of distal fingernail separation and thickening but denied joint stiffness and tenderness. He was otherwise healthy and denied accompanying fevers, chills, or weight loss.

69-Year-Old with Rash on the Axilla and Groin

A 69-year-old man presented with a three-month history of an erythematous rash in the axilla and groin. The lesions were stable with mild pruritus. The patient was referred to dermatology after failed empiric treatment with topical antifungal creams prescribed by his primary care physician. He reports being otherwise healthy and denied a family history of psoriasis.