Difficult-to-treat psoriatic arthritis (D2T PsA): a scoping literature review informing a GRAPPA research project

Abstract

BackgroundPsoriatic arthritis (PsA) is a multifaceted condition with a broad spectrum of manifestations and a range of associated comorbidities. A notable segment of patients with PsA remains resistant to even advanced therapeutic interventions. This resistance stems from myriad causes, including inflammatory and non-inflammatory factors.ObjectivesTo collate and critically assess the various definitions and criteria of difficult-to-treat (D2T PsA present in the literature.MethodsUsing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, we conducted a scoping review in July 2023, searching PubMed, American College of Rheumatology Convergence 2022, European Alliance of Associations for Rheumatology Congress 2023, Google Scholar and cited articles. Selection was made by two independent authors using Rayyan software, and conflicts were adjudicated by a third author. Eligibility criteria for PubMed focused on all article designs that were written in English, with full-text available, from the past decade, excluding only those not defining D2T PsA or targeting other populations.ResultsFrom the 565 references sourced, 15 studies were analysed, revealing considerable variations in defining both ‘active disease’ and ‘resistant PsA’, which was most often termed ‘D2T’ PsA.ConclusionThe definitions and criteria for D2T PsA and for ‘active disease’ are notably heterogeneous, with considerable variation across sources. The ongoing Group for Research and Assessment of Psoriasis and Psoriatic Arthritis initiative stands to bridge these definitional gaps and aims to provide guidance for clinicians and illuminate a path for pharmaceuticals and regulatory agencies to follow.

Deciphering difficult-to-treat psoriatic arthritis (D2T-PsA): a GRAPPA perspective from an international survey of healthcare professionals

“…Similarly, Wendling et al [ 28 ] advocated for a comparable approach in delineating D2T-axSpA, proposing the failure of either ≥2 b/tsDMARDs with different MOAs or ≥3 b/tsDMARDs regardless of their MOA, as criteria. However, as recently illustrated by a scoping review carried by our research team, there is still no consensus regarding the number of drugs that a patient must fail to be classified as D2T-PsA [ 10 ].…”

“…Concurrently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has initiated a key project to define ‘difficult-to-treat’ psoriatic arthritis (D2T-PsA). This initiative began with a scoping review to understand existing definitions and applications of D2T-PsA in the literature [ 10 ]. An important outcome of this review was the introduction of the term ‘complex-to-manage psoriatic arthritis’ (C2M-PsA), which encompasses inclusion of factors such as depression, fatigue and comorbidities that can contribute to persistence of negative symptoms or treatment limitations.…”

Unmet needs in psoriatic arthritis, a narrative review

“…56 In a recent systematic literature review performed by GRAPPA, the definitions found for D2T PsA were variable across the studies: in some cases, this was vaguely described as multiple treatment attempts, while in others it covered from failure to ≥1 TNFi to failures involving ≥2 b/tsDMARDs or even extending to ≥3 b/tsDMARDs. 42 An EULAR survey conducted in 2023 among specialist rheumatologists revealed varied opinions concerning the criteria for defining D2T PsA. 40 The majority of respondents (34.8%) supported a definition of D2T PsA that involved the failure of at least 2 classes of b/tsDMARDs with a pragmatic definition of truly 'refractory PsA' being preferred, indicating 'failing all available classes of b/tsDMARDs' (74%).…”

“…[ 40 ] Indeed, comorbidities and widespread pain contribute to complicated management of patients (what can be term ‘difficult to manage’. [ 41 , 42 ] This emphasizes the need to address both inflammatory and non-inflammatory factors for optimal PsA management, with consideration of all comorbidities in therapeutic decisionmaking. [ 43 ]…”

“…In a recent systematic literature review performed by GRAPPA, the definitions found for D2T PsA were variable across the studies: in some cases, this was vaguely described as multiple treatment attempts, while in others it covered from failure to ≥1 TNFi to failures involving ≥2 b/tsDMARDs or even extending to ≥3 b/tsDMARDs. [ 42 ]…”