SummaryBackground Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28Á8%), PASI 50 (55Á5%) and static Physician's Global Assessment score of 0 or 1 (20Á4%) vs. placebo (5Á8%, 19Á7%, 4Á4%, respectively; P < 0Á001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0Á001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.

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Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g. cell lines), processes or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic and clinical assessment for similarity. The goal of the phase 3 clinical development programme for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints and statistical methods. Based on the clinical trial results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practising clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases.

10503 Background: The IGF1 system has been implicated in sarcoma development and inhibition of IGF1R function has been shown to induce clinical responses in select sarcomas. Methods: Objectives included response rate (RR) and progression-free survival (PFS) to R1507 in patients with recurrent or refractory Ewing's (ES, 2 cohorts- primary refractory vs. others) osteo (OS), synovial (SS), rhabdomyosarcoma (RMS), and other sarcomas. Eligibility included recurrent/refractory measurable disease, age ≥ 12 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered i.v. at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks X 4 and every 12 wks thereafter. A two-stage design (Green and Dahlberg) was used. The endpoint for the primary refractory ES cohort was PFS at week 18 (planned n=65). RR was the primary endpoint for the remaining cohorts (planned n=240). Results: From 12/07–12/08, 203 eligible patients from 29 centers across the US, Europe and Australia were enrolled. Age ranged from 12–85 yrs (median=27 yrs) and 126 were male. Verified histologic subtypes were ES (n=71), OS (n=43), RMS (n=28), SS (n=25), and others (n=25). 15 severe adverse events were reported in 9 patients, the most common being fatigue (n=2), thrombocytopenia (n=2), dehydration (n=2), and hyperglycemia (n=2). Clinically significant activity has been observed in ES, RMS and OS with several dramatic responses seen in ES and RMS. Independent radiologic review is currently ongoing and updated data will be presented. Conclusions: The rapid accrual amongst many centers in diverse geographical locations demonstrates the feasibility of collaborative research in sarcomas. R1507 is well tolerated and a promising new agent for the treatment of various sarcomas. SARC and Roche are collaborating in additional clinical trials to better define the role of R1507 in the treatment of selected sarcomas. [Table: see text]

Introduction This cross-sectional survey was conducted with National Psoriasis Foundation (NPF) to capture treatment perspectives and expectations in patients with psoriasis (PsO) using Patient Needs Questionnaire (PNQ) of Patient Benefit Index (PBI). Methods Adult participants with self-reported diagnosis of PsO responded to the PNQ portion of PBI by indicating how much they valued different treatment attributes. All the treatment goals were captured on a five-point Likert scale (0 = “Not important”, 4 = “Very important”). Treatment goals were obtained for overall population and subgroups based on severity of disease Patient Global Assessment (PGA), age, gender, and Dermatology Life Quality Index (DLQI) total score. All data were expressed as mean and standard deviation [SD]. Results A total of 1200 participants completed the survey (mean age 51.5 years). Top treatment goal in the overall population was “to have confidence in the therapy” (3.46 [1.01]). Unique to the higher severity subgroup (PGA ≥ 3), “to find a clear diagnosis and therapy” was a top five goal and “to get better skin quickly” was for those with lesser severity (PGA < 3). “To be free of itching” (3.36 [0.99]) was the unique goal in the < 40 age group whereas it was “to get better skin quickly” (3.27 [1.12]) in the ≥ 40 group. In women and men, “to be free of itching” (3.38 [1.13]) and “to get better skin quickly” (3.20 [1.09]) were top five goals, respectively. Patients with ≥ 10 DLQI scores expressed higher treatment goal “to regain control of the disease” (3.66 [0.67]) compared to those with ≤ 10 DLQI scores who expressed “to have confidence in the therapy” (3.40 [1.11]) as the topmost treatment goal. Conclusion Our results suggest that in patients with PsO, treatment preferences can vary with different characteristics such as age, severity, and gender as measured by using PNQ. Further exploration of this data will help inform treatment decisions and optimize patient outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02124-2.