Comparability of European League Against Rheumatology-Recommended Pharmacological Treatments of Oral Ulcers Associated with Behçet’s Disease: A Systematic Literature Review of Randomized Controlled Trials

Abstract

Tara Nazareth,1 Erin M Hart,2 Sarah M Ronnebaum,3 Sandhya Mehta,4 Dipen A Patel,3 Ina Kötter5 1Amgen Inc., Thousand Oaks, CA, USA; 2Pharmerit - an OPEN Health Company, New York, NY, USA; 3Pharmerit - an OPEN Health Company, Bethesda, MD, USA; 4Celgene Corporation, Summit, NJ, USA; 5Division of Rheumatology and Systemic Inflammatory Diseases, University Hospital Hamburg Eppendorf and Clinic for Rheumatology and Immunology, Bad Bramstedt, GermanyCorrespondence: Dipen A PatelPharmerit - an OPEN Health Company, Bethesda, MD, USATel [phone]Email [email protected]: Oral ulcers are the cardinal manifestation in Behçet’s disease (BD). The 2018 European League Against Rheumatism (EULAR) recommendations describe treatments for BD-associated oral ulcers with mucocutaneous involvement; however, little comparative effectiveness information for these agents is available. In the absence of head-to-head trials, an indirect treatment comparison (ITC) could provide useful evidence regarding comparative effectiveness of BD treatments. The purpose of this study was to conduct a comparative systematic literature review (SLR) and similarity assessment of randomized controlled trials (RCTs) investigating the oral ulcer-related efficacy outcomes of EULAR-recommended treatments for BD-associated oral ulcers to determine the feasibility of an ITC.Methods: An SLR was performed to identify relevant RCTs indexed in MEDLINE/Embase before May 29, 2019. RCT similarities for the ITC were assessed based on a step-wise process recommended by the International Society for Pharmacoeconomics and Outcomes Research.Results: In total, 317 articles were identified, of which 14 RCTs, reflecting 11 EULAR-recommended treatments, were evaluated in a similarity assessment. Number of oral ulcers, resolution of oral ulcers, and healing time for oral ulcers were identified as the possible oral ulcer-related outcomes. After completing the similarity assessment of these outcomes, it was determined that a robust ITC was infeasible for the three oral ulcer-related outcomes due to heterogeneity in outcomes reporting, study design, and/or patient characteristics. More broadly, the results underscore the need for and consistent use of standardized measures for oral ulcer outcomes to facilitate comparative research.Conclusion: In the absence of head-to-head RCTs and infeasibility of quantitative ITC, comparative assessments for BD-associated oral ulcers are limited, including comparative effectiveness and cost-effectiveness evaluations. Healthcare decision-makers must continue to base treatment decisions on the extent and strength of available evidence (eg, robust RCTs), clinical guidelines, real-world experience, and patient considerations.Keywords: Behçet syndrome, oral ulcer, comparative effectiveness research

Keywords

• behçet syndrome
• oral ulcer
• comparative effectiveness research