In February, Amgen invited Australian dermatologists to the launch of Otezla (apremilast) for patients with chronic plaque psoriasis now listed on the Pharmaceutical Benefits Scheme.1,2 International guest speaker Dr Linda Stein Gold, Director of Dermatology Clinical Research at Henry Ford Health System in Detroit, Michigan was joined by local faculty members Dr Diana Rubel and Associate Professor Peter Foley to discuss the clinical experience and application of Otezla as a post-topical option for patients with chronic plaque psoriasis.
The burden of psoriasis can extend beyond the skin
Psoriasis is recognised as a systemic inflammatory disease caused by dysregulation of the immune system.3 Around 30% of patients with chronic plaque psoriasis develop psoriatic arthritis,4 and patients with severe psoriasis can be at risk of comorbidities including lymphoma and cardiovascular, metabolic, respiratory, and inflammatory gastrointestinal diseases.3,4 Topical agents are a mainstay treatment, but as Dr Stein Gold highlighted to webinar participants “earlier and more appropriate use of systemic therapies could help improve management, it’s just that until now there has been limitations in the systemic management of chronic plaque psoriasis.”3 “Topical therapy isn’t practical for certain manifestations of chronic plaque psoriasis. Depending on the total body surface area (BSA) involvement and the presence of challenging manifestations such as scalp or nail involvement or pruritis, topical therapies may not deliver the results we want.5 Uncontrolled chronic plaque psoriasis, even moderate in severity, has the potential to still greatly impair a patient’s quality of life.6 Lesions that occur on the face, scalp, hands, or genitals can cause psychological and self-esteem issues, while severe itching or pain can interfere with daily activities. That’s where systemic therapy could help fill an unmet need,” explained Dr Stein Gold.5,7
Conventional oral and topical therapies present challenges for physicians and patients that can leave the burden of chronic plaque psoriasis untreated
Despite this high burden of disease, many patients remain undertreated. Dr Stein Gold presented physician and patient surveys that showed first-line topical monotherapy is commonly prescribed even for moderate to severe disease, and that up to 85% of patients have never used systemic oral or biologic therapies.6,8,9 This relates to concerns from both patients and physicians about the long-term safety, tolerability, and efficacy of conventional oral therapies such as methotrexate.10“However, topical therapies also pose challenges for long-term management, which negatively affects compliance,” explained Dr Stein Gold.11 “More severe and extensive disease requires larger quantities of topical agents over longer periods of time, increasing exposure to adverse effects.11 Administration of topical agents may also require complex dosing regimens or application in hard-to-reach areas, becoming time consuming and messy.”11
Otezla® – a post-topical treatment option for chronic plaque psoriasis in Australia
Otezla (apremilast) is an oral phosphodiesterase 4 (PDE4) inhibitor that works intracellularly to modulate anti-inflammatory and pro-inflammatory mediators.2 In Australia, Otezla is approved for adults with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy based on the phase 3, multicentre, randomised, double-blind, placebo-controlled Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) trials of 1257 adults with moderate to severe plaque psoriasis.2 A/Prof. Foley explained how from 1 January 2021, “Otezla was made available to Australian dermatologists on the PBS for the treatment of severe chronic plaque psoriasis that significantly impacts quality of life in patients who have failed treatment with or who are contraindicated or intolerant to methotrexate”
In clinical trials, Otezla significantly reduced clinical manifestations of chronic plaque psoriasis
As Dr Stein Gold presented, both ESTEEM 1 and ESTEEM 2 reached their primary endpoint, with significantly more patients treated with Otezla than with placebo achieving a PASI-75 response (≥75% reduction in Psoriasis Area and Severity Index score) at Week 16 (33% vs 5% in ESTEEM 1; 29% vs 6% in ESTEEM 2; P<0.0001 for both studies).12,13 “Importantly, patients who achieved a response at Week 16 maintained their response through to Week 32 in both studies,12,13 with Otezla-treated patients in ESTEEM 1, who were Week 32 PASI-75 responders, maintaining an 81% to 88% improvement in baseline PASI score during Weeks 32 to 52,” explained Dr Stein Gold.12
Otezla also demonstrated efficacy for subgroups of patients with moderate to severe psoriasis affecting specific body areas, which Dr Stein Gold noted as important considerations for the types of patients you might consider Otezla for. “Compared with placebo, treatment with Otezla resulted in significantly greater responses at Week 16 in patients with scalp, nail, and palmoplantar psoriasis.13,14 Treatment with Otezla also significantly reduced itch severity by 48% at Week 16,12 with improvement in itch observed as early as 2 weeks,13 and improved quality of life.”2,12,13
Dr Stein Gold’s experience with Otezla in her practice has been consistent with the clinical trial experience
In addition to performing as expected in terms of efficacy, Dr Stein Gold also noted that the safety profile is consistent as well. “Pooled safety data from the ESTEEM studies with exposure beyond 3 years supports a long-term safety profile consistent with that observed in the placebo-controlled phase,15 where the most common treatment-related adverse effects were diarrhoea and nausea, affecting <20% of patients, with upper respiratory tract infections, nasopharyngitis, and headaches also affecting 5% to 10% of patients.”12,13 Most adverse effects were mild to moderate in severity.2 Rates of common adverse effects during the first year of exposure were similar but decreased with longer term exposure.15 Otezla was not associated with an increased risk for major cardiac events, malignancy, or opportunistic infection during the 3 years of follow-up.15
During Q&A, Australian dermatologists talked about the day-to-day practicalities of prescribing Otezla
After hearing the clinical data discussion from Dr Stein Gold and A/Prof. Foley’s overview of prescribing Otezla as a Streamlined Authority (11115), webinar participants quizzed the panel on the specifics of titration and how to use the available titration packs, whether any ongoing patient monitoring is required, considerations for patients who are pregnant as well as how Dr Stein Gold’s patients have been going during the coronavirus disease 2019 (COVID-19) pandemic.
- Australian Government Department of Health. Schedule of Pharmaceutical Benefits: Summary of Changes. Available at: www.pbs.gov.au (accessed 6 January 2021).
- Otezla (apremilast) Approved Product Information (www.amgen.com.au/Otezla.PI).
- Reich K. J Eur Acad Dermatol Venereol. 2012;26(suppl 2):3-11.
- Kovitwanichkanont T, et al. Med J Aust. 2020;212(11):528-535.
- Menter A, et al. J Am Acad Dermatol. 2019;80:1029-1072.
- Lebwohl MG, et al. J Am Acad Dermatol. 2014;70:871-881.e1-30.
- Merola JF, et al. Dermatol Ther. 2018;31:e12589.
- Iversen L, et al. J Eur Acad Dermatol Venereol. 2017;31:1188-1195.
- Tveit KS, et al. J Eur Acad Dermatol Venereol. 2019;33:340-354.
- van de Kerkhof PCM, et al. J Eur Acad Dermatol Venereol. 2015;29:2002-2010.
- Menter A, et al. J Am Acad Dermatol. 2009;60:643-659
- Papp K, et al. J Am Acad Dermatol. 2015;73:37-49.
- Paul C, et al. Brit J Dermatol 2015;173:1355–56.
- Rich P, et al. J Am Acad Dermatol. 2016;74:134-142.
- Crowley J, et al. J Am Acad Dermatol 2017;77(2):310–317