1. Kristensen LE, Jorgensen TS, Christensen R, Gudbergsen H, Dreyer L, Ballegaard C, Jacobsson STH, Strand V, Mease PJ, Kjelberg J. Societal Costs and Patients' Experience of Health Inequities Before and After Diagnosis of Psoriatic Arthritis. Ann Rheum Dis 2017; 76: 1495-1501

2. Egeberg A, Kristensen LE, Thyssen JP, Gislason GH, Gottlieb AB, Coates LC, Jullien D, Gisondi P, Gladman DD, Skov L, Mallbris L. Incidence and Prevalence of Psoriatic Arthritis in Denmark;a Nationwide Register Linkage Study. Ann Rheum Dis 2017;76: 1591-1597.

3. Ogdie A. The Preclinical Phase of PsA: A Challenge for the Rheumatologist. 2017;76: 1481-

 

Psoriatic Arthritis (PsA) is an elusive subject for prevalence studies because of the absence of diagnostic criteria and its possible overlap with other articular and even non-articular disorders. Considerable variation [KJ1]  in prevalence and incidence occurs in the literature. Two new PsA studies dealing with the same population and an accompanying editorial are reviewed together because they highlight the ability to address PsA on a population level, advancing our understanding of this condition without the case-selection ascertainment bias that appears to be present in medical center-based cohort studies. 

 

A nationwide register linkage study was performed in Denmark to address the question of incidence and temporal trends for PsA that occur in the general population.  The key here is that all Danish citizens are assigned a unique personal identification number linked to a system that records inpatient and outpatient consultations that contain all primary and secondary diagnoses. In addition, this system is linked to a pharmacy database that records the use of biological and non-biological therapies in this population. The authors observed the incidence of PsA to increase between 1997 and 2011, in contrast to that of PsO which remained stable. This increase was observed mostly among older individuals with a female predominance. Overall, the prevalence of PsA was calculated to be 0.22%, but it was lower when the diagnosis was made only by rheumatologists [KJ2]  . The use of systemic therapies also increased over time in this population, likely reflecting targeted educational initiatives [KJ3]  by pharmaceutical companies.

In a companion article utilizing the same population, the investigators examined the hypothesis that PsA patients face healthcare inequities (by comparison to the general population) [KJ4]  because they have a greater number of co-morbidities.  They compared the healthcare costs, employment status, and personal income of patients both 5 years before and 10 years after the diagnosis of PsA. They studied 10,525 patients with PsA and 20,777 matched controls and found, not surprisingly, that increased healthcare costs, lower income, higher unemployment rates, higher disability risk, and more comorbidities existed in PsA patients as compared to the general population, both in the period prior to diagnosis and after diagnosis.  These data suggest that the increased occurrence of the above factors prior to the diagnosis might contribute to the development of PsA rather than being the result of PsA as is typically assumed to be the case. 

Alexis Ogdie, in a thoughtful and comprehensive editorial, addresses the challenge posed by epidemiologic studies that attempt to identify a 'pre-clinical' phase of a chronic rheumatic disease such as PsA where we do not know when the disease begins. She points out that assigning a starting date for PsA is confounded by the presence of preexisting skin psoriasis which itself could produce systemic inflammation that might result in the health inequity cycles described in Denmark [KJ5]  . She points out a key issue in these types of analysis that could cause a bias by the assignment of a "risk factor" to a condition that might, by itself, be part of the disease as opposed to something truly causal [KJ6]  .  In other words, there is confusion when distinguishing between clinical features that might be causal and those clinical manifestations that permit earlier disease identification.   She further addresses the potential bias caused by the concept of 'depletion of the susceptibles' when examining the risk of development of comorbidities among patients with PsA.  For example, she points out if a study of new cases in a population is started at the time when PsA is diagnosed, we may incorrectly assume a lower incidence of comorbidities because patients who had pre-existing comorbidities would be excluded from the calculations.  Consider the analogy that if we want to identify the true population at risk for GI bleeding after taking an NSAID, we cannot exclude those who had taken an NSAID in the past and did not bleed. 

Dr. Ogdie made an excellent comment describing the strengths of a population-based, large, generalizable, physician diagnosed PsA [KJ7]  registry-linkage study that records important covariates with several years of follow-up.  However, she did urge caution in attempting to infer causality when studying the epidemiology of patients in the so-called 'pre-clinical phase' because of methodological challenges sorting out what is an attributable risk from what is already a disease manifestation. The more we know about PsA the more we have become concerned about long term health outcomes from a societal perspective.  Like all well-done epidemiologic studies, these two studies of PsA should generate questions [KJ8]  about co-morbidities for our translational colleagues to address.

 

- Michael H. Weisman, MD