At the 13th International Congress of Dermatology held virtually in November 2021, Amgen hosted a satellite symposium featuring Peter van de Kerkhof, Professor at Radboud University in the Netherlands and Chief Medical Officer of the International Psoriasis Council, who presented the latest data from the Understanding Psoriatic Disease Leveraging Insights For Treatment (UPLIFT) survey.¹ He was joined by Peter Foley, Associate Professor in the Department of Medicine (Dermatology) at the University of Melbourne, Director of Research at the Skin Health Institute, and Head of Dermatology Research at St Vincent’s Hospital Melbourne, who presented real-world evidence from the Australasian Psoriasis Registry and the Apremilast Clinical Treatment Experience in Psoriasis (APPRECIATE) study in patients with high-impact psoriatic disease.^2,3

Is the burden of psoriasis greater than we realised? The UPLIFT survey uncovered current perceptions of psoriatic disease

In 2012, the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey revealed that many patients who live with psoriatic disease experience a high disease burden as well as a range of comorbidities that can negatively affect their quality of life.⁴ Eight years on, the UPLIFT survey provides an update on patient perceptions and identified persisting areas of unmet need. As Prof. van de Kerkhof explained, re-measuring the impact “really makes sense [because] since 2012, psoriasis treatment options have increased tremendously.” ¹

Prof. van de Kerkhof explained how both surveys included “adult patients reported to have been diagnosed by a healthcare professional with psoriasis or psoriatic arthritis,” and evaluated responses from over 4000 patients and physicians in six countries across Europe and North America.^1,4

Characteristics of the UPLIFT and MAPP surveys^1,4,5

In both surveys, most patients had psoriasis only and a high proportion reported having limited skin involvement, as defined by a body surface area (BSA) score of ≤3 palms. Prof. van de Kerkhof explained how the proportion of patients with a diagnosis of psoriasis plus psoriatic arthritis doubled from 14% in 2012 to 28% in 2020^1,4 – a rise that might indicate “a sign of optimism that increased awareness of doctors and patients about psoriatic arthritis is starting to come.”

Compared with the patient population in the MAPP study, the patient population in the UPLIFT study was younger, included more men, and reported higher rates of certain comorbidities including cancer, depression, diabetes, and inflammatory bowel disease.^1,4 Again, Prof. van de Kerkhof was hopeful “the increased prevalence of these comorbidities may reflect a greater awareness among patients and physicians about the systemic nature of psoriatic disease.”

Discordant perceptions between patients and physicians: UPLIFT 2020

Despite most patients reporting limited skin involvement (BSA ≤3 palms), 58% of patients with limited BSA rated their psoriasis symptoms as moderate or severe with involvement of special areas (e.g., scalp face, palms, soles, nails, or genitals).

Of patients with limited BSA and psoriasis involvement in ≥1 special area, 60% reported their current symptoms as moderate or severe, with 51% of these patients receiving only topical treatment or no treatment. Prof. van de Kerkhof explained that “even when BSA is limited, psoriasis in special locations can cause significant impact to quality of life, which shows that we are undertreating patients with limited BSA but high impact on quality-of-life for the reason that they have special locations involved.”¹

As discovered back in 2012 with the MAPP survey, the UPLIFT survey confirmed differences between patients and dermatologists in their perspectives on psoriatic disease burden and treatment goals.

While patients ranked the type, location, and duration of symptoms as the top 3 factors contributing to their disease severity, dermatologists placed greater importance on the extent of disease (BSA) and its impact on overall quality-of-life.

Similarly, patients ranked reduced itching as their top treatment goal while dermatologists’ top priority was to improve overall quality of life. While both patients and dermatologists consider symptom control and skin clearance of high importance, Prof. van de Kerkhof noted “the subtle but important difference between the total skin clearance desired by patients and near total skin clearance sought by dermatologists.” UPLIFT also found that more patients than dermatologists reported never discussing certain topics during office visits, including joint involvement, related conditions, and the effect of psoriasis on emotional well-being.¹

Another surprise finding from UPLIFT was the ongoing under-treatment of patients with joint pain: in UPLIFT, 58% of patients with a diagnosis of psoriasis only reported joint pain.

These patients reported a higher frequency of comorbidities than patients with no joint pain, especially depression, and were less likely to be prescribed systemic therapy than patients with a diagnosis of psoriatic arthritis. Many of these patients may require referral to a rheumatologist, with 63% reporting involvement of ≤4 joints and 42% returning a positive result on the Psoriasis Epidemiology Screening Tool (PEST ≥3).¹

In his closing advice to colleagues, Prof. van de Kerkhof urged his peers, “let’s better regard, in clinical practice, the signs and symptoms of systemic disease, but also the risk factors involved in the development of comorbidities in our patients. Let’s become more than skin deep.”

Closer to home: Real-world data from the Australasian Psoriasis Registry and the APPRECIATE study

A/Prof. Foley began by highlighting the range of comorbidities experienced by over 1,400 patients with moderate to severe chronic plaque psoriasis recorded in the Australasian Psoriasis Registry.²

“In the real world, compared with phase III clinical trials, patients often have a quite dramatic burden of disease comorbidities. Quite a number of patients that we have on biologics in Australia would not have qualified for entry into phase III studies because of their other illnesses,” he explained.

APPRECIATE: Real-world evidence for apremilast in patients with high impact disease

Reviewing data from APPRECIATE, a recent multinational, real-world, retrospective study of 480 patients with psoriasis who started apremilast and were treated for at least 6 months, A/Prof. Foley showed how in the real world patients had similar demographics and equally impaired baseline Dermatology Life Quality Index (DLQI) scores compared with the patients who participated in the apremilast clinical trials, but less extensive skin involvement as seen by the lower Psoriasis Area and Severity Index (PASI) scores. He noted, “the lower PASI scores but identical DLQI scores show that these are patients with high impact but not necessarily extensive disease,” suggesting that the high proportion of patients with high impact disease may be explained by the high frequency of pruritis (68%) and involvement of highly visible locations (81%).^3,6,7

Of the 347 patients who continued treatment with apremilast for at least 6 months, 69% achieved a PASI-50 and 49% achieved a PASI-75 (reduction in PASI score by 50% or 75% respectively). As well as reduced disease severity (mean PASI reduced from 13.1 to 4.6; mean BSA reduced from 28.3% to 10.9%), these patients also demonstrated improved quality of life (mean DLQI increased from 12.8 to 5.7).  Improvement in DLQI after 6 months of continuous treatment with apremilast was observed across all subgroups of patients with specific manifestations of psoriasis, including scalp and nail involvement and pruritis.³

In APPRECIATE, physicians reported clinical improvement in key clinical signs and symptoms for a high proportion of patients, including overall well-being and clearance of plaque psoriasis. At 6 months, 75% of patients achieved expectations for overall clinical improvement. Patients also reported clinical improvement, as measured by the Patient Benefit Index. A/Prof. Foley showed that “90% of patients with ongoing therapy had clinically meaningful improvement in disease. Those who discontinued, unsurprisingly, half the patients had little or no benefit.”  The physician and patient questionnaires both revealed high levels of agreement that apremilast was associated with a rapid and sustained response, overall and specific skin clearance, improved mood and well-being, and reduced fatigue, itch, and joint pain. For patients continuing treatment at 6 months, 85% of physicians but only 52% of patients were satisfied with overall skin clearance. Patients who remained on treatment had higher scores of effectiveness and satisfaction.³

In the APPRECIATE study, the safety and tolerability data were consistent with the known profile of apremilast. The most common adverse events – diarrhoea, nausea, and headache – were consistent with those observed in the phase III clinical studies and represented the most frequently occurring adverse events leading to discontinuation of treatment. As A/Prof Foley noted, the “low discontinuation was due to nuisance symptoms not end-organ toxicity.”^3,6,7

A/Prof. Foley concluded by highlighting that “these findings really suggest that apremilast may address many of the needs we see in our patients that are voiced by our patients. And this may be an appropriate treatment option for patients who have failed to achieve an adequate response to traditional oral systemic agents or phototherapy.”

References

1. Lebwohl M, Langley RG, Paul C, et al. Evolution of Patient Perceptions of Psoriatic Disease: Results from the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) Survey [published online ahead of print, 2021 Oct 25]. Dermatol Ther (Heidelb). 2021;1-16.
2. Australasian Psoriasis Registry. https://www.skinhealthinstitute.org.au/page/162/australasian-psoriasis-registry (accessed November 2021).
3. Augustin M, Kleyn CE, Conrad C, et al. Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study. J Eur Acad Dermatol Venereol. 2021;35(1):123-134.
4. Lebwohl MG, Bachelez H, Barker J, et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol. 2014;70(5):871-81.e830.
5. van de Kerkhof PC, Reich K, Kavanaugh A, et al. Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey. J Eur Acad Dermatol Venereol. 2015;29(10):2002-2010.
6. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37-49.
7. Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173(6):1387-1399.