Difficult to treat Psoriatic arthritis: Lack of response to methotrexate and prolonged treatment breaks predict refractory disease.

Is it appropriate to use the Eular RA D2T in PsA?

Difficult to treat Psoriatic arthritis: Lack of response to methotrexate and prolonged treatment breaks predict refractory disease.

Devika Dua1, Nicola Gullick1,2

1Department of Rheumatology, University Hospitals Coventry & Warwickshire, 2University of Warwick Medical School

Background: Many patients with Psoriatic arthritis have progressive disease despite multiple therapeutic interventions. Recently, the European League against Rheumatism (EULAR) adopted a formal definition for difficult to treat (D2T) rheumatoid arthritis (RA)1. These include patients who have failed at least two biologics or targeted systemic therapies with signs of active disease and management of clinical signs/symptoms perceived as problematic. Adapting this definition for use in Psoriatic arthritis could be used to identify a similar difficult to treat cohort of patients.

Objectives: We aimed to identify the proportion of our psoriatic arthritis patient cohort who fulfilled the EULAR D2T RA criteria. We went on to investigate disease related factors to see if these were associated with difficult to treat disease.

Methods: We undertook a retrospective notes review of 200 patients with PsA at our centre to identify patients meeting the D2T definition. Additional demographic and disease related factors were also collected for 100 patients for further analysis: patient demographics, smoking and alcohol status, onset of skin and articular disease, pattern of disease at presentation (peripheral -oligoarticular, peripheral – polyarticular or predominant axial disease), cumulative disease activity (skin, tender joints, swollen joints, patient VAS, physician VAS), presence of radiographic damage, response to conventional DMARDs, response to biologics. Cluster analysis of using the k-means cluster algorithm was performed to see if a) the D2T patients clustered together and b) were any patient or disease related factors associated with the D2T cluster.

Results: 30/200 patients (15%) met the difficult to treat definition. Four separate groups of patients were identified with cluster analysis (Figure 1): Axial presentation not D2T, Oligoarticular presentation not D2T, Polyarticular presentation not D2T and D2T. Patients in the D2T phenotype did not have a distinct disease phenotype at presentation. The D2T patients achieved meaningful separation on cluster analysis which was driven by - 1) Complete lack of response to methotrexate therapy, 2) prolonged treatment breaks, 3) high cumulative tender and swollen joints, 4) high cumulative patient and physician global VAS.

Conclusion: The EULAR definition for difficult to treat RA can be applied to patients with Psoriatic Arthritis. Difficult to treat disease is associated with complete lack of response to methotrexate and prolonged breaks in treatment.

Reference: Nagy et al. Ann Rheum Dis 2021;80:31–35.