Trends in Systemic Psoriasis Treatment: Is Psoriasis Still Being Undertreated?

Dear Editor:

Psoriasis is a chronic inflammatory disease with a prevalence of approximately 0.54% in Korea¹,². Psoriasis affects the skin, is commonly associated with various systemic comorbidities, and has a negative impact on health-related quality of life (HRQoL)²,³,⁴. Biologics have considerably revolutionized the treatment and helped doctors and patients manage severe psoriasis appropriately³. We investigated the change in systemic treatment trends among patients with psoriasis using the Health Insurance and Review Assessment (HIRA) data in Korea and compared it with the management of psoriatic arthritis (PsA).

We extracted the data of all the individuals with a history of an outpatient visit or admission with a principal diagnostic code for plaque psoriasis (L40.* except for L40.1, L40.2, and L40.3) or PsA (M07.3, L40.5) from January 2009 to August 2019 (HIRA research data M20200121233). Patients with psoriasis prescribed conventional systemic treatments (acitretin, cyclosporine, and methotrexate), phototherapy, or biologics were considered to have moderate-to-severe psoriasis, while those with PsA prescribed conventional systemic treatments (leflunomide, methotrexate, and sulfasalazine) or biologics were considered to have moderate-to-severe PsA. Biologics included adalimumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab, which are approved in Korea for the treatment of both psoriasis and PsA. The need for Institutional Review Board approval was waived because the dataset consisted of deidentified secondary data (07-2020-3).

Totally, 730,905 patients with psoriasis and 5,377 patients with PsA were identified. Their baseline characteristics are summarized in Supplementary Table 1. Notably, 87.5% of patients with psoriasis were managed in private clinics, whereas less than half of patients with PsA were managed in private clinics. Table 1 demonstrates the number of patients with psoriasis and PsA, as well as those on conventional systemic treatments and biologics. The number of patients with psoriasis managed with conventional systemic treatments gradually increased to 11.4% in 2009 and 13.9% in 2019, while the proportion of patients with PsA on conventional systemic treatments fluctuated from 37.7% to 49.3%. Fig. 1 demonstrates the annual change in the use of biologics in patients with moderate-to-severe psoriasis and PsA. The increasing tendency of prescribing biologics was observed in both the groups (Fig. 1A). In 2012, when an interleukin (IL)-12/23 inhibitor was introduced on the market, 10.1 per 1,000 patients with moderate-to-severe psoriasis and 207.2 per 1,000 patients with moderate-to-severe PsA were treated with biologics, whereas in 2019, 157.1 and 527.3 per 1,000 patients with moderate-to-severe psoriasis and moderate-to-severe PsA, respectively, used biologics (Fig. 1B). Regarding classes of biologics in psoriasis, the majority of patients were treated with the IL-12/23 inhibitor in 2019 (Fig. 1D). However, the growth of IL-23 and IL-17 inhibitors usage was sharp, accounting for nearly 80% of newly prescribed biologics in 2019, making them the more preferred biologics than the IL-12/23 inhibitor (Fig. 1C). The IL-23 inhibitor was most commonly used in 2019.

Table 1. The annual change of systemic treatments use in PsO and PsA.

		2009	2010	2011	2012	2013	2014	2015	2016	2017	2018	~2019.8
PsO, total no.		134,273	133,223	135,305	136,590	139,269	137,685	139,746	142,842	144,344	146,059	127,660
	Conventional systemic treatments*	15,275 (11.4)	14,870 (11.2)	15,535 (11.5)	16,172 (11.8)	16,752(12.0)	17,325 (12.6)	18,394 (13.2)	19,219 (13.5)	20,093 (13.9)	20,850 (14.3)	17,692 (13.9)
	Biologics†	1 (<0.01)	23 (0.02)	80 (0.06)	165 (0.1)	369 (0.3)	513 (0.4)	666 (0.5)	999 (0.7)	1,522 (1.1)	2,513 (1.7)	3,297 (2.6)
PsA, total no.		751	740	808	893	1,013	1,202	1,397	1,503	1,790	2,000	2,014
	Conventional systemic treatments‡	283 (37.7)	323 (43.6)	384 (47.5)	440 (49.3)	463 (45.7)	537 (44.7)	611 (43.7)	671 (44.6)	780 (43.6)	821 (41.1)	772 (38.3)
	Biologics†	54 (7.2)	72 (9.7)	98 (12.1)	115 (12.9)	169 (16.7)	242 (20.1)	313 (22.4)	420 (27.9)	582 (32.5)	732 (36.6)	861 (42.8)

Values are presented as number (%). PsO: psoriasis, PsA: psoriatic arthritis. ^*Included acitretin, cyclosporine, methotrexate, and phototherapy. ^†Included adalimumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab. ^‡Included leflunomide, methotrexate, and sulfasalazine.

Fig. 1. The annual change of biologics use from January 2009 to August 2019 in patients with moderate-to-severe PsO and PsA. (A) The number of newly prescribed biologics in a year and (B) the overall number of biologics use in PsO and PsA. (C) The number of newly prescribed biologics in a year and (D) the overall number of biologics use in patients with PsO grouped by classes of biologics. (E) The number of newly prescribed biologics in a year and (F) the overall number of biologics use in patients with PsA grouped by classes of biologics. TNF-α: tumor necrosis factor-alpha, IL: interleukin, PsO: psoriasis, PsA: psoriatic arthritis.

As expected, the use of biologics was on the rise in both diseases. Biologics were not actively prescribed in psoriasis until the introduction of the IL-12/23 inhibitor; however, new biologics such as IL-17 and IL-23 inhibitors steepened the growth rate of biologics use. The preference between IL-17 and IL-23 inhibitors changed with the introduction of new biologics in the market, so it needs to be monitored in the long term. The increase in the use of biologics is a positive change, and a recent study revealed that biologics were likely to decrease the incidence of major adverse cardiovascular events in patients with moderate-to-severe psoriasis⁵.

Nevertheless, the prescription of biologics in psoriasis was still far less than that in PsA. Moreover, a much lower proportion of patients with psoriasis were treated with conventional systemic treatments. A previous study reported that 41% to 59% of patients with PsA were taking disease-modifying antirheumatic drugs, similar to our findings⁶. On the other hand, patients with moderate-to-severe psoriasis, indicated for systemic treatments, accounted for 22.1% in a multinational study⁷ and 69.0% to 75.3% in the US studies⁸,⁹. In Korea, patients with Psoriasis Area and Severity Index (PASI) ≥10 accounted for 24.9% and body surface area (BSA) ≥10 accounted for 45.9%¹. Taken together, the suggestion that psoriasis is undertreated holds true in Korea as well⁸,⁹,¹⁰. There may be several reasons for this. First, PsA can cause irreversible joint damage if untreated, while psoriasis does not cause major irreversible physical impairments in most cases⁴,⁶. Therefore, both patients with psoriasis and their doctors might be conservative toward using systemic treatments, including biologics, considering the long-term safety, tolerability, efficacy, and cost¹⁰. Second, there is discordance between the patient and doctor in measuring the psoriasis severity⁷,¹⁰. Although doctors consider the location or size of lesions as the most important factors for determining severity, patients feel itching as the most bothersome and most important factor regarding disease severity⁷,¹⁰. Around 50% of patients with BSA ≤3 rated themselves moderate-to-severe⁷. Severity assessment using PASI or BSA does not capture patients’ subjective symptoms, resulting in these disparities. Psoriasis is not organ-destructive like PsA but can be life-destructive considering its negative impact on patient’s HRQoL³,⁴. Third, rheumatologists tend to treat patients more aggressively than dermatologists and are more comfortable with systemic treatments including biologics¹⁰. One survey showed that 54% of dermatologists chose to prescribe topical therapies alone for moderate-to-severe psoriasis due to concerns about long-term safety, tolerability, and efficacy¹⁰. In the case of biologics, doctors were additionally burdened with the time requirement for the patient education and prior authorization requirements as well as costs¹⁰.

Similar to other studies using claims data, the operational definitions of diagnoses and severity based on the diagnostic code and prescription were inevitably different from the actual ones. Nevertheless, our research found the problem of undertreatment of patients with psoriasis also exists in Korea. To reduce the detrimental influence of psoriasis on daily living, it is important to make all proper treatments accessible to patients and let them know the benefit and risk profiles of each treatment. It is advised for doctors to properly assess the severity of psoriasis along with HRQoL, discuss possible treatment options with patients, adjust management accordingly, and not hesitate to use systemic treatments, including biologics. Efforts from both patients and doctors are needed to manage psoriasis adequately.

SUPPLEMENTARY MATERIALS

Supplementary data can be found via http://anndermatol.org/src/sm/ad-21-151-s001.pdf.

Supplementary Table 1

Baseline demographic and disease characteristics of the study cohort