Epidemiology and Medication Pattern Change of Psoriatic Diseases in Taiwan from 2000 to 2013: A Nationwide, Population-based Cohort Study

DISCUSSION

Our study showed that the prevalence rates of psoriatic disease in individuals aged ≥ 16 years, especially PsA, increased in Taiwan from 2000 to 2013. The incidence rates of PsA were significantly higher than those of psoriasis. Our results confirmed that psoriatic disease predominantly affected men. The medication pattern in Taiwan showed an increased usage of DMARD and biologics, while the use of topical therapies decreased.

The prevalence of psoriatic diseases was about 2% in most previous studies. A study by Sheane and Chandran found that PsA accounted for almost 30% of psoriasis¹⁰. Our study found that although the prevalence rates for PsA increased, no significant increases were found for psoriasis, and PsA rates were lower than those reported in Western countries. This phenomenon may be explained, at least in part, by the lower awareness of PsA in Taiwan than in other developed countries, even though an increasing trend was observed in our data (Table 3A and 3B). Because it is a disease with a variety of manifestations, early PsA may not be diagnosed in some patients.

It is possible that a proportion of patients with psoriasis progressed to PsA as a result of comorbidities (e.g., hyperlipidemia and hypertension) and certain risk factors (e.g., smoking, obesity, and low socioeconomic status), which can accelerate development of psoriasis into PsA^{11,12,13,14,15}. In our data, about 50–60% of PsA diagnoses were relative to psoriasis and a mean duration in months (SD) of psoriasis until diagnosis of PsA was 51.81 (36.43; Supplementary Table 3, available from the authors upon request). However, the duration was still underestimated. A review by Ogdie suggested the duration may be 3–5 years¹², which is similar to our findings. The second possibility is that risk factors might also be a trigger for the onset of PsA¹². The third possibility is that psoriasis and PsA are 2 different diseases. A review study by Boehncke, et al suggested that psoriasis does contribute to PsA¹⁶. Based on clinical observations, the authors postulated that psoriasis and PsA were 2 separate entities with no direct pathogenetic link. In genetic studies, a different genetic architecture was found. IL-17 and IL-23 are relevant to psoriasis as well as PsA, while CD8+ T cells might be particularly important in the pathophysiology of PsA. In animal models, both diseases can be readily distinguished from each other, because distinct pathomechanisms contribute to their respective etiologies. In clinical trials, different gene expression in PsA and psoriasis has been demonstrated, with PsA showing a stronger IL-17 gene signature. Taken together, the evidence suggests that psoriasis and PsA may be regarded as 2 sides of the same coin.

In addition, the increasing prevalence and incidence rates in PsA rather than psoriasis might be attributed to the increasing awareness of the disease. Patient and physician knowledge about PsA appears to be gradually increasing. Further, the development of screening tools has likely increased the prevalence and incidence of PsA¹⁷. As is analyzed in a Danish nationwide register linkage study from 1997 to 2011, some reasons are thought provoking; that is, use of questionnaires increased educational initiatives for both patients and physicians. The introduction of the ClASsification for Psoriatic ARthritis criteria may have updated specific symptoms, which would also result in earlier recognition¹⁸.

Our study demonstrated that there was a higher proportion of men than women with psoriatic disease (M:F = 1.82 in 2001; 1.58 in 2013), which is consistent with the finding of a study by Yamamoto, et al in Japan, where the sex ratio (male to female) was 1.9:1 in 2014–2015¹⁹. In contrast, Egeberg, et al found that in Denmark, there was a female predominance from 1998 to 2010¹⁷. In our study, there were significantly increasing trends of PsA in individuals aged 16–31, 32–47, and 48–63 years from 2001 to 2013. Interestingly, some studies have reported that variations in sex ratio in incidence rates differed across all age bands. Two peaks for age of onset in women were found at around 20–29 and 50–59 years of age (Huerta, et al)²⁰, whereas onsets in men were found at around 30–39, 60–69, and 70–79 years of age (Icen, et al)²¹. The male population in our study ranged in age from 16 to 47 years; therefore, the second peak might not easily be seen in our 2000 LHIRD, which might account for the decreased sex ratio in our study from 2000 to 2013.

Biologics and DMARD are classes of medications used in the treatment of rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and psoriatic arthritis. Psoriatic diseases have a variety of symptoms, ranging from skin psoriasis to tenosynovitis^22,23,24,25. Interestingly, in addition to the use of biologics, DMARD are increasingly being applied in dermatological treatments²⁶. The use of many medications, such as oral corticosteriods and NSAID, has decreased significantly, and this decrease may have contributed to the development of new DMARD and biologics. Biologics have revolutionized the treatment of moderate to severe psoriatic diseases²⁷, including both psoriasis and PsA. Even though the use of biologics in Taiwan has increased significantly, the overall rate of usage is still less than that in Western countries, possibly in part because of the strict health insurance reimbursement policy in Taiwan. However, biologics should be used with caution for a number of reasons. Studies in Poland and Denmark showed notable differences before and after diagnosis with PsA in social cost and socioecnomic status, and strikingly, the speed of the rise in treatment cost outpaced the increases in prevalence and incidence rates^28,29. As treatment choices mainly vary according to longterm remission goals, comorbidities, and medication costs, it is imperative to conduct a comprehensive assessment of patients on an individual basis^30,31,32,33.

There are some limitations in our study. First, only medications that are covered by reimbursement in the National Health Insurance program are recorded in the LHIRD, so information on self-paid drugs taken by patients were not included in the analysis. Second, the LHIRD does not contain data on disease or symptom severity, laboratory examinations, or lifestyle habits. Third, the diagnostic codes used in the LHIRD for coding early PsA might have been misclassified as a result of wrong coding or underdiagnosis, which may have led to an underestimation of the prevalence and incidence rates of PsA. Finally, based on the limited data from 2000 to 2013, the incident cases might be the recurrent or remissive patients.

There are some strengths in our study. First, this was a population-based study of physician-diagnosed PsA, so it was more representative than a survey from multiple centers. Second, the LHIRD is essentially a 14-year cohort and thus we could determine change in disease prevalence, incidence, and patterns of medication use from 2000 to 2013.

In this nationwide, population-based cohort study, we found that prevalence and incidence of PsA are increasing, but incidence of psoriasis remains stable. Medication patterns increased for biologics and DMARD, while use of topical therapies decreased.