Therapies for peripheral joint involvement in psoriatic arthritis: a systematic literaure review

Background: Much new information has been reported since the last evidence-based GRAPPA recommendations for the treatment of psoriasis and psoriatic arthritis (PsA). Objectives: We aimed to compile the evidence for the efficacy and safety of established and newly developed drugs targeting the peripheral arthritis domain in PsA so as to provide information for the revised GRAPPA treatment recommendations. Methods: A working group consisting of clinicians and patient research partners (PRPs) was convened. We performed an updated systematic literature review (SLR) of randomized controlled trials (RCTs) for the treatment of PsA, including peripheral arthritis, from the date of the last GRAPPA SLR, from February 19, 2013 to August 28, 2020. The working group reviewed the evidence supporting the efficacy on peripheral arthritis for each class of drug, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, for three patients groups: 1) naïve to treatment ; 2) refractory to conventional (-c)DMARDs ; and 3) with prior biological (-b)DMARD experience. We also evaluated the evidence for non-pharmacological treatments. A set of important outcomes for the peripheral arthritis domain was assessed for each class of medication. The certainty of evidence supporting each class of drugs for each patient group was evaluated. Recommendations were derived through consensus meetings. Results: 87 articles from 52 RCTs were included. For patients with mild disease who are naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and PDE4i, and weakly recommends them for severe disease, where TNFi are preferred over csDMARDs. Other bDMARDs (IL-17i, IL-12/23i, IL- 23i) and JAKi are strongly recommended to treat peripheral arthritis for treatment naïve patients. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL- 23i and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i and JAKi. Certainty of evidence (GRADE) and recommendations for peripheral arthritis domain of PsA for different population groups are shown in Table 1. While the evidence supporting non-pharmacological treatments was low, we derived the recommendations from clinician/PRP expert opinion, included advocating an increase in physical activity, smoking cessation and a healthy diet to control weight gain. Conclusion: Evidence supporting drug treatment for the peripheral arthritis domain of PsA was compiled, providing required information for the revised GRAPPA treatment recommendations. Further work seeking agreement from a broader group of stakeholders is in progress.