SAT0420 EFFICACY OF NON-TUMOUR NECROSIS FACTOR BIOLOGICS AND TARGETED SYSTEMIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS IN THE TREATMENT OF PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: A. Bayley, N. Gullick
Journal: Annals of the Rheumatic Diseases (2020)

Background: Psoriatic arthritis (PsA) is a systemic, inflammatory condition presenting in approximately 30% of patients with psoriasis and associated with functional impairment and a reduced health-related quality of life. Current treatment guidelines recommend non-steroidal anti-inflammatory drugs, conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) and Tumour Necrosis Factor α inhibitors (TNFi). Recent research has focused on alternative biologic medications which target interleukin (IL) 6, 12/23, 17A, 23 and T Cell co-stimulation, as well as targeted synthetic DMARDs (tsDMARDs) including Janus Kinase inhibitors (JAKi) and Phosphodiesterase 4 inhibitors (PDE4i). Evidence of the safety and efficacy, measured using the American College of Rheumatology-20 (ACR20), has been demonstrated leading to the inclusion of several biologics and tsDMARDs in guidelines. However, it can be argued that ACR50, indicating a 50% improvement in disease, is a more clinically relevant outcome measure. Objectives: To conduct a systematic review and meta-analysis of the efficacy (ACR50 response) of non-TNFi biologics and tsDMARDs in the treatment of PsA. Methods: A systematic literature search of Embase, MedLine and Web of Science was undertaken to identify randomised controlled trials (RCTs) investigating efficacy and safety of non-TNFi biologics and tsDMARDs published in English from the inception of the databases to September 2019. The Cochrane Risk of Bias tool was used to assess methodological rigour of included trials. A meta-analysis was performed using a random effects model to estimate odds ratios of ACR 50 response vs placebo. A subgroup analysis was performed using patients with previous TNFi exposure. Results: 21 RCTs were eligible with 6389 participants. Evaluation periods ranged from 12 to 24 weeks. JAKi, PDE4i, IL6i, IL12/23i, IL17Ai and IL23i treatments were more efficacious than placebo for ACR50 response (p&lt;0.001) (Figure 1). Only tofacitinib (JAKi), secukinumab (IL17Ai) and ixekizumab (IL17Ai) were able to demonstrate efficacy at the ACR50 level in participants with prior TNFi exposure (p&lt;0.0001) (Figure 2). All treatments demonstrated an adequate safety profile. Figure 1. Forest plot of achieving American College of Rheumatology-50 with treatment versus placebo M-H, Mantel-Haenzel; CI, confidence interval; JAKi, Janus Kinase inhibitor; PLA, placebo; df, degrees of freedom; PDE4i, Phosphodiesterase 4 inhibitor; IL6Ai, Interleukin 6 inhibitor; IL12/23i, Interleukin 12/23 inhibitor; IL17Ai, Interleukin 17A inhibitor; TNFi, Tumour necrosis factor inhibitor; IL23i, Interleukin 23 inhibitor Figure 2. Forest plot of achieving American College of Rheumatology-50 with treatment versus placebo in tumour necrosis factor inhibitor-exposed subgroup M-H, Mantel-Haenzel; CI, confidence interval; JAKi, Janus Kinase inhibitor; PLA, placebo; df, degrees of freedom; PDE4i, Phosphodiesterase 4 inhibitor; IL6Ai, Interleukin 6 inhibitor; IL12/23i, Interleukin 12/23 inhibitor; IL17Ai, Interleukin 17A inhibitor; IL23i, Interleukin 23 inhibitor Conclusion: Non TNFi biologics and tsDMARDs are able to demonstrate 50% improvement with adequate safety profiles. These therapies are often used in patients who are inadequate responders to TNFi but there is less robust data in this specific patient group. Studies with clinically relevant primary endpoints should be considered in this patient population. Disclosure of Interests: None declared