Anti-citrullinated protein antibodies in patients with psoriatic arthritis

The presence of anti-citrullinated protein antibody may represent only an epiphenomenon in psoriatic arthritis. Dear Editor, PsA is an autoimmune condition with diverse clinical manifestations, including peripheral and axial arthritis, enthesitis, dactylitis and skin and nail psoriasis. Although the peripheral arthritis seen in PsA can have some resemblance to RA, there are several phenotypic characteristics (e.g. distal interphalangeal involvement) that make it a unique entity from RA. Both have the capability for erosive change and functional limitation, highlighting the importance of identifying serum biomarkers to help predict disease severity and response to treatment, which is currently an unmet need in PsA [1]. Traditionally PsA is considered ‘seronegative’, with most patients having a negative RF. PsA patients are also seronegative for the other main RA-associated autoantibody, ACPA, although the prevalence of ACPA is higher among PsA patients than in the general population [2–6]. In RA, ACPA is not only a serological marker of disease, but may have direct immunopathogenic relevance and is associated with a less favourable prognosis. The potential significance of ACPA in PsA has not been fully delineated. The goal of this study was to determine, using a large registry of PsA patients, whether clinical features of PsA patients with ACPA positivity differ compared with ACPA-negative patients. We performed a cross-sectional study of adult patients (age ≥18 years) with physician-diagnosed PsA in the Consortium of Rheumatology Researchers of North America (CORRONA) database. A total of 5363 PsA patients were analysed. All patients provided written informed consent and authorization before enrolment. The institutional review board committee specifically approved this study (New England Independent Review Board no. 120160610). Of 5363 PsA patients in the CORRONA database, 958 (17.7%) had test results for ACPA: 116 (12.1%) were ACPA positive and 842 were ACPA negative. The prevalence of ACPA positivity in the present study (12.1%) was higher than the weighted average (7.4%), but was within the range of values reported from other published studies of PsA patients (see Supplementary Fig. S1, available at Rheumatology online) [1–8]. There were no statistical differences in any measures of disease activity or severity, including radiographic changes, between ACPA-positive and ACPA-negative patients, with the exception of tender joint count (TJC; see Table 1). Interestingly, ACPA-positive patients had a lower average TJC, with a mean difference of −0.89 (95% CI −1.78, −0.02). There was no difference with respect to skin involvement, enthesitis or dactylitis between ACPA-positive and ACPA-negative patients. Regarding radiographic changes, more joint space narrowing was surprisingly noted among ACPA-negative compared with ACPA-positive patients (47.0% vs 36.6%; P = 0.047), although no significant difference was noted with respect to erosions or joint deformity. Clinical characteristics and radiographic data for ACPA-positive and ACPA-negative patients with PsA in the CORONNA database PtGA: patient global assessment of disease activity; VAS: visual analogue scale; PGA: physician global assessment of disease activity; DAS28: 28-joint DAS; CDAI: Clinical Disease Activity Index. P-value calculated from Fisher’s exact test. *Mean difference significant at the 5% level. aFor enthesitis, Fisher’s exact test performed for each site (present vs not present). Clinical characteristics and radiographic data for ACPA-positive and ACPA-negative patients with PsA in the CORONNA database PtGA: patient global assessment of disease activity; VAS: visual analogue scale; PGA: physician global assessment of disease activity; DAS28: 28-joint DAS; CDAI: Clinical Disease Activity Index. P-value calculated from Fisher’s exact test. *Mean difference significant at the 5% level. aFor enthesitis, Fisher’s exact test performed for each site (present vs not present). Further stratification into subgroups based on the presence of RF did not reveal any differences, with the exception of the ACPA-positive/RF-negative group, who had a higher swollen joint count [SJC; mean 4.57 (s.d. 0.77)] than both ACPA-positive/RF-positive and seronegative PsA patients [mean SJC 1.21 (s.d. 0.44) and 2.68 (0.19), respectively; P = 0.003]. In order to establish whether treatment could have affected our results, we analysed the use of immunomodulatory medications between ACPA-positive and ACPA-negative patients. Some studies have found that ACPA positivity is associated with increased use of conventional synthetic DMARDs or biologics, likely due to greater disease severity; however, this was not seen in our cohort [3, 4]. No difference was found between the two groups with respect to any current or previously used medication (including NSAIDs, corticosteroids, MTX, other DMARDs and biologics; P = 0.877). There was also no difference with respect to smoking status between the two groups (P = 0.335), contrary to what has been previously reported in RA. Our findings of ACPA having no association with disease activity are consistent with the findings of Alenius et al. [6] but in contrast with a number of studies suggesting a potential correlation of ACPA positivity with a more severe disease phenotype [2–5]. In a large observational study of PsA patients preparing to start biologic therapy, Behrens et al. [8] found that ACPA positivity was associated with a higher SJC, increased disease activity and higher rates of erosive joint disease. Despite this, our ACPA-positive patients were not found to have increased disease activity or severity, including no difference in radiographic erosions. Our study population is reflective of PsA patients seen in everyday clinical practice. ACPA status was tested in 17.7% of patients. The reason for obtaining the CCP status in these patients is not known; however, it might be expected that any selection bias this could introduce would have led to more severe disease among ACPA-positive patients. For whatever reason ACPA was tested, a positive test result did not seem to confer worse disease activity or radiographic changes in our cohort. In conclusion, these data from a large cohort of PsA patients in clinical practice show no difference in disease activity or severity, including radiographic changes and the use of immunomodulating medications between ACPA-positive and ACPA-negative patients. The data suggest that, in contrast to RA, the presence of ACPA positivity may represent only an epiphenomenon in PsA. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article. Supplementary data are available at Rheumatology online.

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