Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis, one of the most common autoimmune skin diseases affecting 2-3% of the population. Despite many advances in disease pathogenesis and therapeutics, approximately half of PsA patients continue to have active disease despite treatment. Therefore, it is imperative to test new treatment modalities including non-pharmacologic therapies and novel management strategies. While randomized controlled trials (RCTs) can address efficacy, or whether a drug can work, the homogenous population selected for inclusion in RCTs is not generalizable to the broader population of patients with PsA (a highly heterogeneous disease). By contrast, pragmatic trials test the effectiveness of management strategies in real-world clinical practice as opposed to the highly controlled settings in RCTs. Many important questions facing patients with PsA (e.g., comparative effectiveness) can be addressed with pragmatic trials. However, before this approach can be launched effectively, there is a fundamental need to identify appropriate outcome measures for PsA pragmatic trials. Currently the primary outcome in PsA RCTs, is the American College of Rheumatology 20% Response Criteria (ACR20), an outcome designed for rheumatoid arthritis, a substantially different inflammatory arthritis. Furthermore, the ACR criteria have intrinsic weaknesses that ultimately limit feasibility for a pragmatic trial, including the need for a blood test at two time points and underperformance in the most common PsA subpopulation (the half of patients with less than three swollen and tender joints at therapy initiation). The ultimate goal of this proposal is to prepare pragmatic trials in PsA trials that will encompass all relevant subgroups of patients. Three objectives are envisioned: 1) Examine response in the heterogeneous population of patients that can be enrolled in pragmatic trials and compare those to the subset of patients who would be eligible for a traditional RCT; 2) Define the optimal set of outcomes for use in a pragmatic trial; and 3) Examine how subgroups (e.g., sex, phenotypes, comorbidities) affect outcome measurement. We will address the aims in a prospective observational cohort study conducted within the multicenter Psoriatic Arthritis Research Collaborative (PARC). The four centers will also be the sites for the proposed pragmatic trial. At completion of the Aims, we will have all of the necessary components to initiate a pragmatic trial for PsA: outcomes will be selected, stratification variables identified, sample size calculated, and data collection methods solidified. Additionally, we will identify expectations for treatment response in clinical practice, calculate minimal clinically important improvement, and examine how subgroups affect measurement of response. The results from the proposed studies will additionally inform outcome measures for traditional RCTs and clinical practice.
Pragmatic trials can address the effectiveness of therapies in patients with psoriatic arthritis (PsA) (e.g., comparative effectiveness of two drugs or the effectiveness of non-pharmacologic therapies) as opposed to randomized controlled trials that test efficacy. This study aims to define the appropriate outcome measures and expected response rates for pragmatic trials such that all of the components for a pragmatic trial will be ready for implementation at completion of the award.
| Leung, Ying Ying; Ogdie, Alexis; Orbai, Ana-Maria et al. (2018) Classification and Outcome Measures for Psoriatic Arthritis. Front Med (Lausanne) 5:246 |
