More Than Skin Deep: Insights into Clinical Challenges in Psoriatic Arthritis

MADRID—In recent years, the features that make psoriatic arthritis (PsA) distinct from rheumatoid arthritis (RA) have gained increasing attention and allowed for a better understanding of the disease. Recently, a review article in RMD Open described how PsA includes asymmetric joint involvement, may involve the axial spine and may be seronegative for rheumatoid factor (RF) and cyclic citrullinated peptide (CCP). All of these features are not as common in RA. Moreover, differences in the pathogenesis of PsA and RA explain why the specificity and efficacy of certain therapies vary between the two diseases.¹

Although understanding the differences between PsA and other forms of inflammatory arthritis is important, so too is recognizing the variations in PsA phenotypes in patients, as well as how these individual subpopulations should be treated.

At the 2019 European Congress of Rheumatology (EULAR), June 12–15, during a session titled, The Multiple Rheumatological Faces of Psoriatic Arthritis, Laura Coates, MBChB, MRCP, PhD, a clinician scientist and senior clinical research fellow at the National Institute for Health Research at the University of Oxford, England, described the five classic subtypes of patients with PsA. As noted in prior research from 1973, these patient subtypes are:

1. Patients with classic PsA, with distal interphalangeal joint involvement;
2. Patients with arthritis mutilans;
3. Seronegative patients with symmetric patterns of joint involvement similar to RA;
4. Patients with predominant axial spine involvement; and
5. Patients with single or few finger or toe joints involved, typically with scattered distal interphalangeal joint, proximal interphalangeal joint and metatarsophalangeal joint involvement.²

It’s this last group that includes patients with monoarthritis or oligoarthritis, a cohort traditionally regarded as distinct from patients with polyarthritis (i.e., individuals with five or more joints involved by PsA). Dr. Coates noted that even the simple step of classifying patients is not always straightforward. A study evaluated 500 patients with oligoarticular PsA with a 28-joint count and then re-evaluated them with a 68-tender and 66-swollen joint count. The 28-joint count missed 21% of patients with tender joints and 27% of patients with swollen joints. This study implies that a full 66/68 joint count is important for assessing disease activity in PsA patients and properly classifying patients as oligoarticular or polyarticular.³

In comparing monoarticular/oligoarticular and polyarticular PsA patients, Dr. Coates pointed to work from the U.K. This research showed that although the groups differed by age, sex, disability score and symmetry, no differences existed between them in terms of seropositivity for RF and CCP, enthesitis, or spinal pain and stiffness. And aside from entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the groups.⁴

These studies raise several questions about how different the monoarticular/oligoarticular and polyarticular PsA patients truly are from one another and if the distinction between these groups continues to be as clinically relevant as once believed.

The questions are further underscored by work from more than 20 years ago, which demonstrated that, over time, patients can move from the monoarticular/oligoarticular subtype to polyarticular subtype—and vice versa, in rarer cases. Investigators found that, among patients who started with monoarticular PsA, 33% evolved into oligoarticular and 56% into polyarticular disease over 10 years. Among those patients starting with oligoarticular disease, 78% evolved into polyarticular disease over the same duration of follow-up.⁵

It should be noted that recent use of ultrasound technology has further indicated the distinction in groups may be different than what seems to be clinically apparent. In a study of 80 patients with early oligoarthritis, 644 joints were evaluated by clinical exam and by ultrasound. The ultrasound evaluation detected synovitis in 33% of joints that were not found to have synovitis with physical exam alone. Moreover, in almost two-thirds of patients, evidence of subclinical disease was seen on ultrasound, and one-third of patients could be reclassified as polyarticular based on ultrasound findings, compared with findings from clinical assessment only.⁶

Clinical Implications

Dr. Coates concluded the session with the question: Can clinicians extrapolate findings from clinical trials in PsA to both subtypes of patients—those with polyarticular disease, as well as those with monoarticular/oligoarticular disease?

The question is important given the characteristics of patients in the large phase 3 drug trials used to understand the efficacy of various treatment modalities for PsA. Dr. Coates demonstrated the mean number of tender joint counts for inclusion in the trials was around 20 joints and the mean number of swollen joints was 10–15. This clearly indicates these trials are enrolling polyarticular PsA patients at a higher rate than those with monoarticular/oligoarticular disease. A study in Iceland indicated that two-thirds of PsA patients in that country who are treated with tumor necrosis factor inhibitor therapy would not have qualified for the randomized clinical trials performed on these medications because these patients had too few tender/swollen joints to meet the inclusion criteria.⁷

Although more recent drug trials have begun enrolling higher numbers of patients with fewer tender and/or swollen joints, the issue remains that the study populations used to test old and new PsA medications do not represent the entire population of patients. Thus, clinicians are left with the challenge of selecting an appropriate therapy for a patient in the absence of data specific to that patient. Although this issue is not completely unique to PsA, it’s perhaps more prevalent when making PsA treatment decisions than when making RA treatment decisions.

The remainder of the session included high-yield case discussions of the approach to a patient with solitary enthesitis and treatment decisions in patients with oligoarticular disease who may or may not evolve over time.

As Dr. Coates noted, the future of the field will likely benefit from a better understanding of the similarities and differences in subpopulations of patients with varying joint involvement and from the use of composite measures to evaluate response to therapy. As the old adage goes, PsA is more than skin deep. And rheumatologists’ understanding of the condition needs to become increasingly nuanced to positively affect the lives of patients with this disease.

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Jason Liebowitz, MD, recently completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his MD. He is currently in practice with Arthritis, Rheumatic, and Back Disease Associates, New Jersey.

References

1. Merola JF, Espinoza LR, Fleischmann R. Distinguishing rheumatoid arthritis from psoriatic arthritis. RMD Open. 2018 Aug 13;4(2):e000656.
2. Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum. 1973;3(1):55–78.
3. Coates LC, FitzGerald O, Gladman DD, et al. Reduced joint counts misclassify patients with oligoarticular psoriatic arthritis and miss significant numbers of patients with active disease. Arthritis Rheum. 2013 Jun;65(6): 1504–1509.
4. Helliwell PS, Porter G, Taylor WJ, et al. Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis than rheumatoid arthritis. Ann Rheum Dis. 2007 Jan;66(1):113–117.
5. Jones SM, McHugh NJ. Subgroups in psoriatic arthritis. Br J Rheumatol. 1994 Aug;33(8):789.
6. Wakefield RJ, Green MJ, Marzo-Ortega H, et al. Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease. Ann Rheum Dis. 2004 Apr;63(4):382–385.
7. Runarsdottir EE, Gunnarsdottir AI, Love TJ, et al. The majority of patients with psoriatic arthritis are not eligible for randomized clinical trials. Clin Exp Rheumatol. 2018 Nov–Dec;36(6):1068–1073.