FRI0114 ABATACEPT IN EARLY RHEUMATOID ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW AND NETWORK META-ANALYSIS

Abstract

Background: Rheumatoid arthritis (RA) is a wide-spread and debilitating disorder that is becoming increasingly relevant in an aging global population. Identifying and treating RA early in disease course is critical for preventing disability and joint damage. Objectives: The goal of this systematic literature review (SLR) and metaanalysis was to compare the relative efficacy of abatacept (ABA) to other currently recommended therapies for patients with early RA. Methods: We followed Cochrane guidelines for conducting intervention reviews. Population of interest was adult patients with active RA for £2 years treated with recommended therapies per the 2015 ACR guidelines as well as targeted synthetic therapies. Studies of interest were randomized controlled trials (RCTs) and observational studies. Outcomes included ACR50, DAS28, radiographic change, and adverse events where available. A search from January 1998 to June 2018 was performed on MEDLINE®, Embase, and the Cochrane CENTRAL databases. Additionally, a hand-search was performed on US and European clinical trials registries from January 2005 to June 2018 and conference proceedings from ACR and EULAR from 2014 to 2018. A Bayesian network metaanalysis (NMA) was performed on the DOC Data™ platform for the RCTs with reported results on ACR50, DAS28 remission, total withdrawal, and withdrawal due to adverse events. Results: We identified 90 publications on 69 unique trials reporting efficacy and safety outcomes in patients with early RA, including 43 RCTs and 26 observational studies. The included studies were low risk as assessed by the Cochrane Collaboration's tool for assessing risk of bias. The studies were predominantly double-blind phase III or IV trials. Twenty-eight trials were included in the NMA evaluating ABA (n=1 trial), ABA+MTX (n=2), ADA+MTX (n=6), CTZ+MTX (n=2), ETN (n=1), ETN +MTX (n=1), HCQ+SSZ+MTX (n=1), HCQ+SSZ+Pred+MTX (n=1), IFX +MTX (n=4), MTX (n=21), MPred+MTX (n=2), MPred+Pred+MTX (n=1), Pred+SSZ+MTX (n=2), Pred+MTX (n=4), Pred (n=1), SSZ (n=4), SSZ +MTX (n=2), TCZ (n=2), TCZ+MTX (n=2), TOF (n=2), and TOF+MTX (n=2). Abatacept as monotherapy was similar to the combination of ABA and methotrexate for efficacy outcomes, ACR 50 (ABA vs ABA+MTX RR 0.82 [95% CI 0.51-1.35]), and DAS28 Remission (RR 0.76 [95% CI 0.39- 1.49]), as well as for all-cause withdrawal (RR 1.8 [95% CI 0.91-3.2]) and withdrawal due to adverse events (RR 2.35 [95% CI 0.69-7.38]). Both ABA as monotherapy and ABA+MTX were similar to all other comparators (as monotherapy or combination therapy) with respect to main efficacy and safety outcomes. Data reported in observational studies was in concert with the RCT analysis. Conclusion: The results of this NMA demonstrate similar efficacy between ABA and other biologics both as monotherapy and in combination with traditional DMARDS in early RA. Further investigation and comparison of different treatment options for early RA is warranted as the growing evidence base evolves in favor of using more novel therapies for RA. ABA=abatacept; ADA=adalimumab; CTZ=certolizumab; ETN= etanercept; HCQ=hydroxychloroquine, IFX= infliximab, MPred= methylprednisolone, MTX=methotrexate; Pred=prednisone, SSZ=sulfasalazine, TCZ= tocilizumab, TOF=tofacitinib.